{"id":3390,"date":"2024-03-25T16:30:29","date_gmt":"2024-03-25T08:30:29","guid":{"rendered":"http:\/\/oncolab.cn\/index.php\/2024\/03\/25\/cell%ef%bc%9asmarcal1%e6%98%af%e4%bf%83%e8%bf%9b%e8%82%bf%e7%98%a4%e5%85%8d%e7%96%ab%e9%80%83%e9%80%b8%e7%9a%84%e5%a4%a9%e7%84%b6%e5%85%8d%e7%96%ab%e4%bf%a1%e5%8f%b7%e5%92%8cpd-l1%e8%a1%a8%e8%be%be\/"},"modified":"2024-03-25T16:30:29","modified_gmt":"2024-03-25T08:30:29","slug":"cell%ef%bc%9asmarcal1%e6%98%af%e4%bf%83%e8%bf%9b%e8%82%bf%e7%98%a4%e5%85%8d%e7%96%ab%e9%80%83%e9%80%b8%e7%9a%84%e5%a4%a9%e7%84%b6%e5%85%8d%e7%96%ab%e4%bf%a1%e5%8f%b7%e5%92%8cpd-l1%e8%a1%a8%e8%be%be","status":"publish","type":"post","link":"http:\/\/oncolab.cn\/index.php\/2024\/03\/25\/cell%ef%bc%9asmarcal1%e6%98%af%e4%bf%83%e8%bf%9b%e8%82%bf%e7%98%a4%e5%85%8d%e7%96%ab%e9%80%83%e9%80%b8%e7%9a%84%e5%a4%a9%e7%84%b6%e5%85%8d%e7%96%ab%e4%bf%a1%e5%8f%b7%e5%92%8cpd-l1%e8%a1%a8%e8%be%be\/","title":{"rendered":"Cell\uff1aSMARCAL1\u662f\u4fc3\u8fdb\u80bf\u7624\u514d\u75ab\u9003\u9038\u7684\u5929\u7136\u514d\u75ab\u4fe1\u53f7\u548cPD-L1\u8868\u8fbe\u7684\u53cc\u91cd\u8c03\u8282\u5668"},"content":{"rendered":"
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<\/section>\n<\/section>\n
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\u6742\u5fd7\u540d\u79f0<\/strong>\uff1aCell<\/span><\/p>\n

\u53d1\u8868\u65e5\u671f<\/strong>\uff1a2024.01.25<\/p>\n

DOI<\/strong>\uff1a10.1016\/j.cell.2024.01.008.<\/p>\n

PubMed<\/strong>\uff1ahttps:\/\/pubmed.ncbi.nlm.nih.gov\/38301646\/<\/p>\n

\u5f71\u54cd\u56e0\u5b50<\/strong>\uff1a64.5<\/p>\n<\/section>\n<\/section>\n<\/section>\n

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\u5185\u5bb9\u7b80\u4ecb<\/strong><\/p>\n<\/section>\n

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\u57fa\u56e0\u7ec4\u4e0d\u7a33\u5b9a\u6027\u53ef\u4ee5\u89e6\u53d1\u4fc3\u8fdb\u80bf\u7624\u6392\u65a5\u7684\u764c\u75c7\u5185\u6e90\u6027\u5929\u7136\u514d\u75ab\u5e94\u7b54\u3002\u7136\u800c\uff0c\u764c\u7ec6\u80de\u7ecf\u5e38\u901a\u8fc7\u8fc7\u8868\u8fbe\u514d\u75ab\u68c0\u67e5\u70b9\u8c03\u8282\u5242\uff08\u5982PD-L1\uff09\u6765\u9003\u907f\u8fd9\u4e9b\u5e94\u7b54\u3002\u5728\u8fd9\u91cc\uff0c\u6211\u4eec\u53d1\u73b0SNF2\u5bb6\u65cfDNA\u8f6c\u4f4d\u9176SMARCAL1\u662f\u4e00\u4e2a\u4fc3\u8fdb\u80bf\u7624\u514d\u75ab\u9003\u9038\u7684\u5173\u952e\u56e0\u5b50\uff0c\u5b83\u901a\u8fc7\u6291\u5236\u5929\u7136\u514d\u75ab\u4fe1\u53f7\u548c\u8bf1\u5bfcPD-L1\u4ecb\u5bfc\u7684\u514d\u75ab\u68c0\u67e5\u70b9\u5e94\u7b54\u7684\u53cc\u91cd\u673a\u5236\u53d1\u6325\u4f5c\u7528\u3002\u5728\u673a\u5236\u4e0a\uff0cSMARCAL1\u9650\u5236\u4e86\u5185\u6e90\u6027DNA\u635f\u4f24\uff0c\u4ece\u800c\u5728\u764c\u7ec6\u80de\u751f\u957f\u8fc7\u7a0b\u4e2d\u6291\u5236\u4e86cGAS-STING\u4f9d\u8d56\u7684\u4fe1\u53f7\u4f20\u5bfc\u3002\u540c\u65f6\uff0c\u5b83\u4e0eAP-1\u5bb6\u65cf\u6210\u5458JUN\u5408\u4f5c\uff0c\u7ef4\u6301PD-L1\u8f6c\u5f55\u8c03\u63a7\u5143\u4ef6\u4e0a\u7684\u67d3\u8272\u8d28\u53ef\u8bbf\u95ee\u6027\uff0c\u4ece\u800c\u4fc3\u8fdb\u764c\u7ec6\u80de\u4e2dPD-L1\u7684\u8868\u8fbe\u3002SMARCAL1\u7684\u4e27\u5931\u963b\u788d\u4e86\u80bf\u7624\u7ec6\u80de\u5728\u57fa\u56e0\u7ec4\u4e0d\u7a33\u5b9a\u6027\u53cd\u5e94\u4e2d\u8bf1\u5bfcPD-L1\u7684\u80fd\u529b\uff0c\u589e\u5f3a\u4e86\u6297\u80bf\u7624\u514d\u75ab\u5e94\u7b54\uff0c\u5e76\u5728\u5c0f\u9f20\u9ed1\u8272\u7d20\u7624\u6a21\u578b\u4e2d\u4f7f\u80bf\u7624\u5bf9\u514d\u75ab\u68c0\u67e5\u70b9\u963b\u65ad\u654f\u611f\u3002\u603b\u7684\u6765\u8bf4\uff0c\u8fd9\u4e9b\u7814\u7a76\u63ed\u793a\u4e86SMARCAL1\u662f\u764c\u75c7\u514d\u75ab\u6cbb\u7597\u7684\u4e00\u4e2a\u6709\u6f5c\u529b\u7684\u9776\u70b9\u3002<\/p>\n<\/section>\n<\/section>\n<\/section>\n

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\u521b\u65b0\u6027\u53ca\u7814\u7a76\u610f\u4e49<\/strong><\/p>\n<\/section>\n

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\u8fd9\u7bc7\u6587\u7ae0\u7684\u6838\u5fc3\u521b\u65b0\u6027\u5728\u4e8e\u53d1\u73b0\u4e86SMARCAL1\u8fd9\u4e00\u86cb\u767d\u8d28\u5728\u4fc3\u8fdb\u80bf\u7624\u514d\u75ab\u9003\u9038\u4e2d\u7684\u53cc\u91cd\u8c03\u8282\u4f5c\u7528\u3002\u7814\u7a76\u6307\u51faSMARCAL1\u901a\u8fc7\u4e24\u79cd\u673a\u5236\u4fc3\u8fdb\u80bf\u7624\u7684\u514d\u75ab\u9003\u9038\uff1a\u4e00\u662f\u6291\u5236\u764c\u7ec6\u80de\u5185\u5929\u7136\u514d\u75ab\u4fe1\u53f7\u7684\u6fc0\u6d3b\uff0c\u4e8c\u662f\u4fc3\u8fdbPD-L1\uff08\u4e00\u79cd\u514d\u75ab\u68c0\u67e5\u70b9\u86cb\u767d\uff09\u7684\u8868\u8fbe\uff0c\u4ece\u800c\u6291\u5236\u514d\u75ab\u7cfb\u7edf\u5bf9\u80bf\u7624\u7684\u653b\u51fb\u3002\u6b64\u5916\uff0c\u7814\u7a76\u8fd8\u53d1\u73b0\uff0cSMARCAL1\u7684\u7f3a\u5931\u80fd\u591f\u589e\u5f3a\u6297\u80bf\u7624\u514d\u75ab\u5e94\u7b54\uff0c\u5e76\u5728\u5c0f\u9f20\u9ed1\u8272\u7d20\u7624\u6a21\u578b\u4e2d\u63d0\u9ad8\u5bf9\u514d\u75ab\u68c0\u67e5\u70b9\u963b\u65ad\u6cbb\u7597\u7684\u654f\u611f\u6027\u3002<\/p>\n

\u7814\u7a76\u610f\u4e49\u65b9\u9762\uff0c\u8fd9\u9879\u5de5\u4f5c\u63ed\u793a\u4e86SMARCAL1\u4f5c\u4e3a\u80bf\u7624\u514d\u75ab\u8c03\u8282\u7684\u5173\u952e\u56e0\u5b50\uff0c\u4e3a\u764c\u75c7\u514d\u75ab\u6cbb\u7597\u63d0\u4f9b\u4e86\u65b0\u7684\u9776\u70b9\u3002\u8fd9\u4e00\u53d1\u73b0\u4e0d\u4ec5\u6df1\u5316\u4e86\u6211\u4eec\u5bf9\u80bf\u7624\u514d\u75ab\u9003\u9038\u673a\u5236\u7684\u7406\u89e3\uff0c\u4e5f\u4e3a\u5f00\u53d1\u9488\u5bf9SMARCAL1\u7684\u65b0\u578b\u764c\u75c7\u6cbb\u7597\u7b56\u7565\u63d0\u4f9b\u4e86\u7406\u8bba\u57fa\u7840\u3002<\/p>\n<\/section>\n<\/section>\n<\/section>\n

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\u6570\u636e\u56fe<\/strong><\/p>\n<\/section>\n

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\u56fe1\uff1a\u5728MDA-MB-436\u4e09\u9634\u6027\u4e73\u817a\u764c\u7ec6\u80de\u4e2d\u5e94\u7528FACS\u7684CRISPR-Cas9\u57fa\u56e0\u7b5b\u9009\u7814\u7a76<\/strong><\/p>\n

(A) sgRNA\u6587\u5e931\u9488\u5bf9\u7684\u57fa\u56e0\u7f51\u7edc\u3002\u8282\u70b9\uff08\u57fa\u56e0\uff09\u7684\u5927\u5c0f\u8868\u793a\u6839\u636ePrePPI\u6570\u636e\uff0c\u5404\u8282\u70b9\uff08\u57fa\u56e0\uff09\u4e4b\u95f4\u7684\u9057\u4f20\u548c\u7269\u7406\u4ea4\u4e92\u4f5c\u7528\uff08\u7070\u8272\u8fde\u7ebf\uff09\u7684\u9891\u6b21\u3002<\/p>\n

(B) \u8bc6\u522b\u6838\u5185IRF3\u548cPD-L1\u8c03\u8282\u56e0\u5b50\u7684CRISPR\u7b5b\u9009\u6d41\u7a0b\u56fe\u3002\u5728\u9009\u53d6\u7ecf\u6162\u75c5\u6bd2sgRNA\u6587\u5e931\u8f6c\u5bfc\u7684MDA-MB-436\u7ec6\u80de\u540e\uff0c\u5c06\u7ec6\u80de\u6574\u4f53\u6536\u96c6\uff08\u672a\u5206\u9009\uff09\u6216\u6839\u636e\u6307\u6807\u5206\u4e3a\u4e09\u4e2a\u4e9a\u7fa4\u3002\u901a\u8fc7\u9ad8\u901a\u91cf\u6d4b\u5e8f\u6280\u672f\u786e\u5b9a\u4e0d\u540c\u7ec6\u80de\u4e9a\u7fa4\u4e2dsgRNA\u7684\u76f8\u5bf9\u4e30\u5ea6\u3002<\/p>\n

(C\u2013E) \u6839\u636e\u68c0\u6d4b\u7ec4\u4e2d\u5404sgRNA\u7684\u76f8\u5bf9\u4e30\u5ea6\uff0c\u5bf9sgRNA\u6587\u5e931\u76ee\u6807\u57fa\u56e0\u8fdb\u884c\u6392\u540d\uff0c\u5e76\u5c55\u793a\u5176\u6807\u51c6\u5316\u03b2\u5206\u6570\u7684\u5206\u5e03\u3002\u4f7f\u7528\u672a\u5206\u9009\u7684\u7ec6\u80de\u7fa4\u4f5c\u4e3a\u53c2\u7167\uff0c\u901a\u8fc7MAGeCK\u6700\u5927\u4f3c\u7136\u4f30\u8ba1\u6cd5\uff08MLE\uff09\u8ba1\u7b97\u5f97\u5230IRF3\u9ad8\u8868\u8fbe\/PD-L1\u4f4e\u8868\u8fbe\uff08C\uff09\u3001IRF3\u9ad8\u8868\u8fbe\/PD-L1\u9ad8\u8868\u8fbe\uff08D\uff09\u548cIRF3\u4f4e\u8868\u8fbe\/PD-L1\u4f4e\u8868\u8fbe\uff08E\uff09\u4e9a\u7fa4\u4e2d\u57fa\u56e0\u7684\u6807\u51c6\u5316\u03b2\u5206\u6570\u3002\u7ea2\u8272\u548c\u84dd\u8272\u70b9\u5206\u522b\u4ee3\u8868\u4e0esgRNA\u4e30\u5ea6\u589e\u52a0\u548c\u51cf\u5c11\u76f8\u5173\uff08\u03b2\u5206\u6570\u6b63\u503c\u6216\u8d1f\u503c\uff0cp < 0.05\uff09\u7684\u57fa\u56e0\u3002<\/p>\n<\/section>\n<\/section>\n<\/section>\n

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\u56fe2\uff1aSMARCAL1\u7f3a\u9677\u4e0b\u7684PD-L1\u8868\u8fbe\u53ca\u764c\u7ec6\u80de\u56fa\u6709\u5148\u5929\u514d\u75ab\u5206\u6790<\/strong><\/p>\n

(A) \u514d\u75ab\u5370\u8ff9\u663e\u793a\u4e86\u7528\u6307\u5b9asiRNA\u5904\u7406\u7684MDA-MB-436\u7ec6\u80de\u3001MDA-MB-436\u5bf9\u7167\u7ec6\u80de\u6216SMARCAL1- KO\u514b\u9686\u4e2dSMARCAL1\u3001PD-L1\u548cvinculin\u7684\u6c34\u5e73\u3002s.e.\u8868\u793a\u77ed\u66dd\u5149\uff1bl.e.\u8868\u793a\u957f\u66dd\u5149\u3002<\/p>\n

(B) \u514d\u75ab\u5370\u8ff9\u56fe\u663e\u793a\u4e86\u5728(A)\u4e2d\u63cf\u8ff0\u7684\u7ec6\u80de\u7cfb\u4e2dSMARCAL1\u3001\u78f7\u9178\u5316IRF3\uff08pIRF3 S386\uff09\u3001\u6574\u4f53IRF3\uff0c\u4ee5\u53catubulin\u6216vinculin\u7684\u6c34\u5e73\u3002<\/p>\n

(C) \u76f8\u5bf9\u4e8e\u5bf9\u7167MDA-MB-436\u7ec6\u80de\uff0c\u901a\u8fc7VIPER\u786e\u5b9aSMARCAL1\u7f3a\u5931\u7ec6\u80de\uff08Query 1\uff09\u548cSMARCAL1-KO\u514b\u9686\uff08Query 2-4\uff09\u5728\u6307\u5b9a\u7684\u6807\u5fd7\u57fa\u56e0\u96c6\uff08MSigDB\uff09\u5185\u7684\u6d3b\u6027\u8bc4\u5206\u3002<\/p>\n

(D) \u4e0e\u5bf9\u7167MDA-MB-436\u7ec6\u80de\u76f8\u6bd4\uff0cSMARCAL1-KO\u514b\u9686#1\u5728\u6807\u5fd7\u57fa\u56e0\u96c6\uff08MSigDB\uff09\u4e2d\u7684\u6807\u51c6\u5316\u5bcc\u96c6\u8bc4\u5206\uff08NESs\uff09\u3002<\/p>\n

(E) \u5bf9\u7167MDA-MB-436\u7ec6\u80de\uff0cSMARCAL1-KO\u514b\u9686#1\u5728\u6307\u5b9a\u7684\u6807\u5fd7\u57fa\u56e0\u96c6\uff08MSigDB\uff09\u4e2d\u7684\u57fa\u56e0\u96c6\u5bcc\u96c6\u5206\u6790\u3002<\/p>\n

(F) \u5b9e\u65f6\u5b9a\u91cfPCR\uff08RT-qPCR\uff09\u5206\u6790\u5bf9\u7167\u7ec4\u53caSMARCAL1-KO #1 MDA-MB-436\u7ec6\u80de\u4e2dIFNA\u3001IFNB1\u3001\u9009\u5b9a\u7684\u5e72\u6270\u7d20\u523a\u6fc0\u57fa\u56e0\uff08ISGs\uff09\u548c\u4fc3\u708e\u7ec6\u80de\u56e0\u5b50\u7684mRNA\u6c34\u5e73\u3002\u6570\u636e\u5c55\u793a\u4e86\u5728SMARCAL1-KO #1\u4e0e\u5bf9\u7167\u7ec6\u80de\u4e2d\u57fa\u56e0\u8868\u8fbe\u7684\u500d\u6570\u53d8\u5316\u3002\u67f1\u72b6\u56fe\u8868\u793a\u72ec\u7acb\u751f\u7269\u91cd\u590d\u5b9e\u9a8c\u7684\u5e73\u5747\u503c\u00b1SEM\uff08\u70b9\u72b6\uff09\u3002p\u503c\u901a\u8fc7\u591a\u91cd\u672a\u914d\u5bf9t\u68c0\u9a8c\u8ba1\u7b97\u5f97\u51fa\u3002<\/p>\n

(G) \u7ec6\u80de\u56e0\u5b50\u6297\u4f53\u9635\u5217\u5c55\u793a\u4e86\u5bf9\u7167\u7ec4\u548cSMARCAL1-KO #1 MDA-MB-436\u7ec6\u80de\u4e2d\u8868\u8fbe\u7684\u7ec6\u80de\u56e0\u5b50\u3002\u53c2\u8003\u548c\u80cc\u666f\u4fe1\u53f7\u5c55\u793a\u3002<\/p>\n

(H) \u5728(G)\u5b9e\u9a8c\u4e2d\uff0c\u5bf9\u7167\u7ec4\u548cSMARCAL1-KO #1 MDA-MB-436\u7ec6\u80de\u7684\u7ec6\u80de\u56e0\u5b50\u6c34\u5e73\u76f8\u5bf9\u4e8e\u53c2\u8003\u4fe1\u53f7\u8fdb\u884c\u4e86\u6807\u51c6\u5316\u3002<\/p>\n

(I) \u514d\u75ab\u5370\u8ff9\u56fe\u663e\u793a\u4e86\u5bf9\u7167\u7ec4\u548cSMARCAL1-KO #1 MDA-MB-436\u7ec6\u80de\u4e2dSMARCAL1\u3001\u78f7\u9178\u5316STAT1\uff08pSTAT1 Y701\uff09\u3001\u6574\u4f53STAT1\u548ctubulin\u7684\u6c34\u5e73\u3002<\/p>\n

(J) RNA\u6d4b\u5e8f\u5206\u6790\u7684\u706b\u5c71\u56fe\uff0c\u6bd4\u8f83SMARCAL1-KO #1\u548c\u5bf9\u7167MDA-MB-436\u7ec6\u80de\uff08\u5047\u53d1\u73b0\u7387[FDR] < 0.05\uff09\u3002\u7ea2\u70b9\u8868\u793a\u5728(D)\u4e2d\u7684\u6807\u5fd7\u57fa\u56e0\u96c6\u4e2dSMARCAL1-KO #1\u76f8\u5bf9\u4e8e\u5bf9\u7167\u7ec6\u80de\u8868\u8fbe\u663e\u8457\u589e\u52a0\u7684\u57fa\u56e0\u3002CD274\uff08PD-L1\uff09\u57fa\u56e0\u4ee5\u84dd\u8272\u6807\u793a\u3002<\/p>\n

(K) \u5728\u7ecf\u6307\u5b9asiRNA\u5904\u7406\u7684MDA-MB-436\u7ec6\u80de\u3001MDA-MB-436\u5bf9\u7167\u7ec6\u80de\u548cSMARCAL1-KO\u514b\u9686\u4e2d\uff0cPD-L1 mRNA\u6c34\u5e73\u7684RT-qPCR\u5206\u6790\u3002\u8868\u8fbe\u6570\u636e\u7684\u5206\u6790\u548c\u8868\u793a\u65b9\u6cd5\u5982(F)\u6240\u8ff0\u3002p\u503c\u901a\u8fc7\u5355\u56e0\u7d20\u65b9\u5dee\u5206\u6790\uff08one-way ANOVA\uff09\u8ba1\u7b97\u3002<\/p>\n<\/section>\n<\/section>\n<\/section>\n

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\n

\u56fe3\uff1aSMARCAL1\u7f3a\u5931\u7ec6\u80de\u4e2d\u56fa\u6709\u514d\u75ab\u4fe1\u53f7\u7684\u5206\u6790<\/strong><\/p>\n

(A) MDA-MB-436\u5bf9\u7167\u7ec6\u80de\u548cSMARCAL1-KO\u514b\u9686\u7684DAPI\u548ccGAS\u67d3\u8272\u56fe\u50cf\uff08\u5de6\u56fe\uff09\u3002\u663e\u793a\u5177\u6709\u4e00\u4e2a\u6216\u591a\u4e2a\u5fae\u6838\u7684\u7ec6\u80de\u767e\u5206\u6bd4\uff08\u4e2d\u56fe\uff09\u4ee5\u53ca\u5e26\u6709cGAS\u9633\u6027\u5fae\u6838\u7684\u7ec6\u80de\u767e\u5206\u6bd4\uff08\u53f3\u56fe\uff09\u3002\u67f1\u72b6\u56fe\u4ee3\u8868\u72ec\u7acb\u751f\u7269\u5b66\u91cd\u590d\u5b9e\u9a8c\u7684\u5e73\u5747\u503c\u00b1SEM\uff08\u70b9\u72b6\u56fe\uff09\u3002\u901a\u8fc7\u5355\u56e0\u7d20\u65b9\u5dee\u5206\u6790(one-way ANOVA)\u786e\u5b9ap\u503c\u3002<\/p>\n

(B) MDA-MB-436\u5bf9\u7167\u7ec6\u80de\u548cSMARCAL1-KO\u514b\u9686\u5185\u90e8cGAMP\u6c34\u5e73\u7684\u76f8\u5bf9\u503c\u3002\u56fe\u5f62\u8868\u793a\u548c\u7edf\u8ba1\u5206\u6790\u65b9\u6cd5\u540c(A)\u3002<\/p>\n

(C) \u514d\u75ab\u5370\u8ff9\u663e\u793a\u7ecf\u6307\u5b9asiRNA\u5904\u7406\u7684MDA-MB-436\u7ec6\u80de\u3001\u5bf9\u7167\u7ec4\u548cSMARCAL1-KO #1\u7ec6\u80de\u4e2dSMARCAL1\u3001cGAS\u3001\u78f7\u9178\u5316IRF3\uff08pIRF3 S386\uff09\u3001\u6574\u4f53IRF3\u548ctubulin\u7684\u6c34\u5e73\u3002<\/p>\n

(D) \u5b9e\u65f6\u5b9a\u91cfPCR\uff08RT-qPCR\uff09\u5206\u6790\u5bf9\u7167\u7ec4\u548cSMARCAL1-KO #1 MDA-MB-436\u7ec6\u80de\u5728\u7ecf\u6307\u5b9asiRNA\u5904\u7406\u540e\uff0c\u9009\u5b9a\u7684\u5e72\u6270\u7d20\u523a\u6fc0\u57fa\u56e0\uff08ISGs\uff09\u548c\u4fc3\u708e\u7ec6\u80de\u56e0\u5b50\u7684mRNA\u6c34\u5e73\u3002\u6570\u636e\u8868\u793a\u4e0e\u5bf9\u7167siRNA\u5904\u7406\u7ec6\u80de\u76f8\u6bd4\u57fa\u56e0\u8868\u8fbe\u7684\u500d\u6570\u53d8\u5316\u3002\u56fe\u5f62\u8868\u793a\u65b9\u6cd5\u540c(A)\u3002\u7edf\u8ba1\u5206\u6790\u901a\u8fc7\u591a\u91cd\u672a\u914d\u5bf9t\u68c0\u9a8c\u8fdb\u884c\u3002<\/p>\n

(E) \u672c\u7814\u7a76\u4e2d\u4f7f\u7528\u7684SMARCAL1\u53ca\u5176\u7a81\u53d8\u4f53\u793a\u610f\u56fe\u3002<\/p>\n

(F) \u5728\u7528SMARCAL1 WT\u6216\u6307\u5b9a\u7a81\u53d8\u4f53\u91cd\u6784\u7684SMARCAL1\u7f3a\u5931MDA-MB-436\u7ec6\u80de\u4e2d\uff0c\u5177\u6709\u4e00\u4e2a\u6216\u591a\u4e2a\u5fae\u6838\u7684\u7ec6\u80de\u767e\u5206\u6bd4\uff08\u5de6\u56fe\uff09\u6216\u5e26\u6709cGAS\u9633\u6027\u5fae\u6838\u7684\u7ec6\u80de\u767e\u5206\u6bd4\uff08\u53f3\u56fe\uff09\u3002\u56fe\u5f62\u8868\u793a\u548c\u7edf\u8ba1\u5206\u6790\u65b9\u6cd5\u540c(A)\u3002<\/p>\n

(G) \u4e0eWT\u76f8\u6bd4\uff0c\u5728\u7528\u6307\u5b9aSMARCAL1\u7a81\u53d8\u4f53\u8f6c\u67d3\u7684SMARCAL1\u7f3a\u5931MDA-MB-436\u7ec6\u80de\u4e2d\u5185\u90e8cGAMP\u7684\u6c34\u5e73\u3002\u56fe\u5f62\u8868\u793a\u548c\u7edf\u8ba1\u5206\u6790\u65b9\u6cd5\u540c(A)\u3002<\/p>\n<\/section>\n<\/section>\n<\/section>\n

\n
\n
\n
<\/section>\n<\/section>\n
\n

\u56fe4\uff1aSMARCAL1\u5bf9PD-L1\u8868\u8fbe\u7684\u8c03\u8282<\/strong><\/p>\n

(A) \u7528\u4e8e\u8bc4\u4f30\u7ecf\u6307\u5b9asiRNA\u5904\u7406\u540e\uff0c\u590d\u5236\u548c\u975e\u590d\u5236RPE1-hTERT TP53-\/- <\/sup>\u6216 U2OS-Fucci\u7ec6\u80de\u4e2dPD-L1\u6c34\u5e73\u7684\u5b9e\u9a8c\u6d41\u7a0b\u793a\u610f\u56fe\u3002<\/p>\n

(B) \u514d\u75ab\u5370\u8ff9\u56fe\u663e\u793a\u4e86\u5728\u57f9\u517b\u4e8e\u751f\u957f\u6216\u9965\u997f\u57f9\u517b\u57fa\u4e2d\u7684RPE1-hTERT TP53-\/-<\/sup>\u7ec6\u80de\u4e2d\uff0c\u7b2c4\u5929\u7ecf\u6307\u5b9asiRNA\u5904\u7406\u540e\uff0c\u7b2c7\u5929SMARCAL1\u3001PD-L1\u548cvinculin\u7684\u6c34\u5e73\uff0c\u5982(A)\u6240\u793a\u3002<\/p>\n

(C) \u5b9e\u65f6\u5b9a\u91cfPCR\uff08RT-qPCR\uff09\u5206\u6790\u4e86\u5982(B)\u6240\u8ff0\u57f9\u517b\u7684RPE1-hTERT TP53-\/-<\/sup> \u7ec6\u80de\u7ecf\u6307\u5b9asiRNA\u5904\u7406\u540ePD-L1 mRNA\u6c34\u5e73\u3002\u6570\u636e\u8868\u793a\u4e0e\u5bf9\u7167\u7ec6\u80de\uff08RPE1-hTERT TP53-\/- <\/sup>\u7ec6\u80de\u7ecf\u5bf9\u7167siRNA\u5904\u7406\u540e\u5728\u751f\u957f\u57f9\u517b\u57fa\u4e2d\u57f9\u517b\uff09\u76f8\u6bd4PD-L1\u8868\u8fbe\u7684\u500d\u6570\u53d8\u5316\u3002\u67f1\u72b6\u56fe\u4ee3\u8868\u6280\u672f\u91cd\u590d\u7684\u5e73\u5747\u503c\u00b1SEM\uff08\u70b9\u72b6\u56fe\uff09\uff0c\u4e3a\u4e24\u4e2a\u72ec\u7acb\u751f\u7269\u91cd\u590d\u5b9e\u9a8c\u3002p\u503c\u901a\u8fc7\u5355\u56e0\u7d20\u65b9\u5dee\u5206\u6790\uff08one-way ANOVA\uff09\u8ba1\u7b97\u3002<\/p>\n

(D) \u70ed\u56fe\u663e\u793a\u4e86MDA-MB-436\u7ec6\u80de\u4e2d\u901a\u8fc7CUT&RUN\u6280\u672f\u786e\u5b9a\u7684H3K4me3\u5cf0\u4f4d\u70b9\u7684IgG\u548cSMARCAL1\u4fe1\u53f7\u3002RPKM\u8868\u793a\u6bcf\u767e\u4e07\u6620\u5c04\u8bfb\u6570\u6bcf\u5343\u78b1\u57fa\u7684\u8bfb\u6570\u3002<\/p>\n

(E) \u70ed\u56fe\u663e\u793a\u4e86MDA-MB-436\u7ec6\u80de\u4e2d23,245\u4e2a\u7f16\u7801\u86cb\u767d\u7684\u57fa\u56e0\u5728\u8f6c\u5f55\u8d77\u59cb\u4f4d\u70b9\uff08TSS\uff09\u524d2kb\u548c\u8f6c\u5f55\u7ec8\u6b62\u4f4d\u70b9\uff08TES\uff09\u540e2kb\u533a\u57df\u5185\u7684IgG\u3001SMARCAL1\u3001H3K4me3\u548cH3K27me3 CUT&RUN\u4fe1\u53f7\uff08\u6309\u57fa\u56e0\u957f\u5ea6\u6807\u51c6\u5316\u5e76\u6309H3K4me3\u4fe1\u53f7\u6392\u5e8f\uff09\u3002<\/p>\n

(F) \u63a7\u5236\u7ec4\u4e0eSMARCAL1-KO #1-2 MDA-MB-436\u7ec6\u80de\u4e4b\u95f4\u5171\u6709\u548c\u72ec\u7279\u7684ATAC-seq\u5cf0\u503c\u6570\u91cf\u3002\u72ec\u7279\u5cf0\u503c\u548c\u5171\u6709\u5cf0\u503c\u5206\u522b\u4ee3\u8868\u81f3\u5c11\u5728\u5355\u4e2a\u6570\u636e\u96c6\u7684\u4e00\u4e2a\u751f\u7269\u91cd\u590d\u5b9e\u9a8c\u4e2d\u548c\u6240\u6709\u6570\u636e\u96c6\u4e2d\u5b58\u5728\u7684\u5cf0\u503c\u3002<\/p>\n

(G) \u63a7\u5236\u7ec4\u4e0eSMARCAL1-KO #1 MDA-MB-436\u7ec6\u80de\u4e2dCD274\uff08PD-L1\uff09\u4f4d\u70b9\u7684\u6807\u51c6\u5316ATAC-seq\u8f68\u8ff9\uff08\u6bcf\u767e\u4e07\u8ba1\u6570\uff09\u3002\u6bcf\u6761\u8f68\u8ff9\u4ee3\u8868\u4e09\u4e2a\u72ec\u7acb\u751f\u7269\u91cd\u590d\u5b9e\u9a8c\u7684\u5408\u5e76\u3002\u6807\u8bc6\u7684\u5cf0\u503c\uff08P1, 5450318\u20135450905; P2, 5455316\u20135455499; P3, 5459366\u20135459591\uff09\u88ab\u9ad8\u4eae\u663e\u793a\u3002MDA-MB-436\u7ec6\u80de\u4e2dPD-L1\u4f4d\u70b9\u7684H3K27ac ChIP-seq\u8f68\u8ff9\u6765\u81ea\u516c\u5f00\u53ef\u7528\u7684\u6570\u636e\u96c6\uff08GSE85158\uff09\u3002<\/p>\n

(H) \u9488\u5bf9P3\u5cf0\u4f4d\u70b9\u4f7f\u7528dCas9-KRAB-MeCP2\uff08\u9876\u90e8\uff09\u7684CRISPRi\u5b9e\u9a8c\u6d41\u7a0b\u793a\u610f\u56fe\u3002\u5b9e\u65f6\u5b9a\u91cfPCR\uff08RT-qPCR\uff09\u5206\u6790\u5728\u7ecf\u6307\u5b9asiRNA\u5904\u7406\u540e\u5e76\u8f6c\u67d3\u4e86dCas9-KRAB-MeCP2\u548c\u6307\u5b9asgRNAs\u7684MDA-MB-436\u7ec6\u80de\u4e2dPD-L1\u548cSMARCAL1 mRNA\u6c34\u5e73\uff08\u5e95\u90e8\uff09\u3002\u6570\u636e\u8868\u793a\u5728\u6307\u5b9a\u6761\u4ef6\u4e0b\uff0c\u76f8\u5bf9\u4e8e\u7ecf\u5bf9\u7167siRNA\u5904\u7406\u5e76\u8f6c\u67d3\u4e86dCas9-KRAB-MeCP2\u548c\u975e\u9776\u5411sgRNA\u7684MDA-MB-436\u7ec6\u80de\u4e2d\u57fa\u56e0\u8868\u8fbe\u7684\u500d\u6570\u53d8\u5316\u3002\u67f1\u72b6\u56fe\u4ee3\u8868\u72ec\u7acb\u751f\u7269\u91cd\u590d\u5b9e\u9a8c\u7684\u5e73\u5747\u503c\u00b1SEM\uff08\u70b9\u72b6\u56fe\uff09\u3002p\u503c\u901a\u8fc7\u591a\u91cd\u672a\u914d\u5bf9t\u68c0\u9a8c\u8ba1\u7b97\u3002<\/p>\n

(I) \u514d\u75ab\u5370\u8ff9\u56fe\u663e\u793a\u4e86\u8868\u8fbedCas9-KRAB-MeCP2\u7684MDA-MB-436\u7ec6\u80de\uff08MDA-MB-436-CRISPRi\uff09\u5728\u7ecf\u6307\u5b9asgRNAs\u548csiRNAs\u5904\u7406\u540e\uff0cSMARCAL1\u3001PD-L1\u548ctubulin\u7684\u6c34\u5e73\u3002<\/p>\n

(J) ChIP-qPCR\u5206\u6790SMARCAL1-FLAG\u548cRNA\u805a\u5408\u9176II\uff08RNAPII\uff09\u5728P1\u548cP3\u5cf0\u4f4d\u70b9\u7684\u57fa\u56e0\u7ec4\u533a\u57df\u6216GAPDH\u542f\u52a8\u5b50\u4f5c\u4e3a\u5bf9\u7167\u7684\u5360\u636e\u60c5\u51b5\u3002\u6570\u636e\u4ee3\u8868\u4e09\u6b21\u72ec\u7acb\u5b9e\u9a8c\u7684\u7ed3\u679c\uff0c\u5e76\u663e\u793a\u6280\u672f\u91cd\u590d\u7684\u5e73\u5747\u503c\u00b1SEM\u3002p\u503c\u901a\u8fc7\u591a\u91cd\u672a\u914d\u5bf9t\u68c0\u9a8c\u8ba1\u7b97\u3002<\/p>\n

(K) \u514d\u75ab\u5370\u8ff9\u663e\u793a\u7ecfSMARCAL1 siRNA\u5904\u7406\u5e76\u8865\u5145\u4e86\u91ce\u751f\u578b\u6216\u7a81\u53d8SMARCAL1 cDNAs\u6216\u8f7d\u4f53\u5bf9\u7167\u7684MDA-MB-436\u7ec6\u80de\u4e2dSMARCAL1\u3001PD-L1\u548ctubulin\u7684\u6c34\u5e73\u3002<\/p>\n<\/section>\n<\/section>\n<\/section>\n

\n
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<\/section>\n<\/section>\n
\n

\u56fe5\uff1a\u8bc6\u522b\u4e0eSMARCAL1\u534f\u540c\u4fc3\u8fdbPD-L1\u8868\u8fbe\u7684\u8f6c\u5f55\u56e0\u5b50<\/strong><\/p>\n

(A) \u5229\u7528CRISPR\u7b5b\u9009\u6280\u672f\u8bc6\u522b\u8c03\u8282SMARCAL1\u4f9d\u8d56\u7684PD-L1\u8868\u8fbe\u7684\u8f6c\u5f55\u56e0\u5b50\uff08TFs\uff09\u3002\u5728\u9009\u62e9\u4e86\u8f6c\u5bfc\u4e86sgRNA\u6587\u5e932\u7684\u5bf9\u7167\u6216SMARCAL1-KO #1 MDA-MB-436\u7ec6\u80de\u540e\uff0c\u6536\u96c6\u4e86\u4f5c\u4e3a\u4e00\u4e2a\u6df7\u5408\u6c60\uff08\u672a\u5206\u7c7b\uff09\u7684\u7ec6\u80de\u6216\u6309\u6240\u793a\u5206\u9009\u7684\u7ec6\u80de\u3002\u901a\u8fc7\u4e8c\u4ee3\u6d4b\u5e8f\u786e\u5b9a\u4e0d\u540c\u7ec6\u80de\u7fa4\u4f53\u4e2dsgRNA\u7684\u4e30\u5ea6\u3002<\/p>\n

(B) \u6839\u636eMAGeCK RRA\u8f93\u51fa\u7684\u6b63\u5411\u9009\u62e9\u5206\u6570\uff0c\u5bf9sgRNA\u6587\u5e932\u9776\u5411\u7684\u57fa\u56e0\u8fdb\u884c\u4e86\u6392\u540d\u805a\u5408\u5206\u6570\u5206\u5e03\uff08RRA\uff09\u7684\u663e\u793a\u3002\u7c89\u7ea2\u70b9\u4ee3\u8868\u4e0e\u5bcc\u96c6\u7684sgRNA\u76f8\u5173\u7684\u57fa\u56e0\uff08\u6b63\u7684\u5bf9\u6570\u500d\u6570\u53d8\u5316\u548cp < 0.05\uff09\u3002<\/p>\n

(C) \u70ed\u56fe\u663e\u793a\u4e86\u901a\u8fc7RT-qPCR\u6d4b\u91cf\u7684\u5728\u5bf9\u7167\u548cSMARCAL1-KO #1 MDA-MB-436\u7ec6\u80de\u4e2d\u8f6c\u5bfc\u4e86\u6307\u5b9asgRNA\u540e\u7684PD-L1 mRNA\u6c34\u5e73\u7684\u4e09\u4e2a\u751f\u7269\u5b66\u91cd\u590d\u7684\u5e73\u5747\u503c\u3002\u4f7f\u7528\u6b27\u51e0\u91cc\u5f97\u8ddd\u79bb\u548cWard\u65b9\u6cd5\u8fdb\u884c\u805a\u7c7b\u5206\u6790\u3002\u8be6\u89c1\u9644\u8868S3\u3002<\/p>\n

(D) \u7528BioID\u5b9e\u9a8c\u8bc6\u522bSMARCAL1\u76f8\u4e92\u4f5c\u7528\u86cb\u767d\u7684\u793a\u610f\u56fe\u3002\u5c06\u8868\u8fbeBirA*\u86cb\u767d\u6216\u4e0eWT\u6216\u7a81\u53d8SMARCAL1\u86cb\u767d\u878d\u5408\u7684BirA*\u7684MDA-MB-436\u7ec6\u80de\u4e2d\u7684\u751f\u7269\u7d20\u5316\u86cb\u767d\u901a\u8fc7\u4eb2\u548c\u7d20\u62c9\u4e0b\u5b9e\u9a8c\u6355\u83b7\uff0c\u7136\u540e\u8fdb\u884c\u8d28\u8c31\u5206\u6790\uff08\u5de6\u56fe\uff09\u3002\u663e\u793a\u4e86\u4e0eBirA*\u5bf9\u7167\u76f8\u6bd4\uff0c\u5728\u6307\u5b9a\u62c9\u4e0b\u5b9e\u9a8c\u4e2d\u5bcc\u96c6\u7684\u901a\u8fc7\u8d28\u8c31\u5206\u6790\u9274\u5b9a\u7684\u86cb\u767d\u8d28\u6570\u91cf\uff08\u53f3\u56fe\uff09\u3002\u8be6\u89c1\u9644\u8868S4\u3002<\/p>\n

(E) \u6839\u636e\u8d28\u8c31\u5728MDA-MB-436\u7ec6\u80de\u4e2d\u901a\u8fc7\u4eb2\u548c\u7d20\u62c9\u4e0b\u5b9e\u9a8c\u6355\u83b7\u7684\u751f\u7269\u7d20\u5316\u86cb\u767d\u7684\u6307\u5b9aBirA*\u878d\u5408\u86cb\u767d\uff0c\u5f97\u5230\u7684JUN\u80bd\u6bb5\u5f3a\u5ea6\u7684\u6807\u51c6\u5316\u5bcc\u96c6\u3002\u6570\u636e\u4ee5\u76f8\u5bf9\u4e8eBirA*\u5bf9\u7167\u7684\u6307\u5b9a\u62c9\u4e0b\u5b9e\u9a8c\u4e2dJUN\u80bd\u6bb5\u5f3a\u5ea6\u7684\u53d8\u5316\u500d\u6570\u5448\u73b0\u3002<\/p>\n

(F) \u4f7f\u7528\u6297SMARCAL1\u3001\u6297RPA\u548c\u6297JUN\u6297\u4f53\uff0c\u5355\u72ec\u6216\u7ed3\u5408\u4f7f\u7528\uff0c\u5728MDA-MB-436\u7ec6\u80de\u4e2d\u5f97\u5230\u7684PLA\u6591\u70b9\u6570\u91cf\u3002\u6570\u636e\u6765\u6e90\u4e8e\u4e09\u4e2a\u72ec\u7acb\u7684\u751f\u7269\u5b66\u91cd\u590d\u5b9e\u9a8c\uff0c\u6bcf\u4e2a\u70b9\u4ee3\u8868\u6bcf\u4e2a\u7ec6\u80de\u7684PLA\u6591\u70b9\u6570\u91cf\u3002\u4e2d\u503c\u5df2\u6807\u51fa\u3002<\/p>\n

(G) \u4f7f\u7528Homer\u7b97\u6cd5\uff0c\u4ee5SMARCAL1\u7ed3\u5408\u7684\u67d3\u8272\u8d28\u533a\u57df\u4e3a\u8f93\u5165\u5cf0\u503c\uff0c\u8fdb\u884cde novo\u53d1\u73b0\u7684\u57fa\u5e8f\u5206\u6790\u6240\u9274\u5b9a\u7684\u6240\u6709\u57fa\u5e8f\u7684p\u503c\u5206\u5e03\u3002\u663e\u793a\u4e86\u524d\u4e09\u540d\u57fa\u5e8f\uff08#1\u7c7bNFY\uff1b#2\u5bcc\u542bG\u7684\u57fa\u5e8f\uff1b#3 AP-1\/JUN\u7c7b\uff09\u3002<\/p>\n

(H) \u70ed\u56fe\u5c55\u793a\u4e86MDA-MB-436\u7ec6\u80de\u4e2d\uff0c\u4e0d\u540cJUN\u8017\u7aed\u72b6\u6001\u4e0b\u7684IgG\u4e0eSMARCAL1 CUT&RUN\u4fe1\u53f7\uff0c\u8fd9\u4e9b\u4fe1\u53f7\u5b9a\u4f4d\u5728\u86cb\u767d\u7f16\u7801\u57fa\u56e0\u7684\u8f6c\u5f55\u8d77\u59cb\u4f4d\u70b9\uff08TSS\uff09\u524d2kb\u53ca\u8f6c\u5f55\u7ec8\u6b62\u4f4d\u70b9\uff08TES\uff09\u540e2kb\u8303\u56f4\u5185\uff08\u9876\u90e8\u70ed\u56fe\u9762\u677f\uff09\u3002\u540c\u6837\u663e\u793a\u4e86JUN\u8017\u7aed\u6216\u672a\u8017\u7aed\u7684MDA-MB-436\u7ec6\u80de\u4e2d\uff0cIgG\u4e0eSMARCAL1\u4fe1\u53f7\u76f8\u5bf9\u4e8eH3K4me3\u548cJUN\u5cf0\u7684\u5b9a\u4f4d\uff08\u5e95\u90e8\u4e24\u4e2a\u9762\u677f\uff09\u3002<\/p>\n

(I) \u5b9e\u65f6\u5b9a\u91cfPCR\uff08RT-qPCR\uff09\u5206\u6790\u5728\u8868\u8fbedCas9-KRAB-MeCP2\uff08MDA-MB-436-CRISPRi\uff09\u548c\u6307\u5b9asgRNAs\u7684MDA-MB-436\u7ec6\u80de\u4e2dPD-L1 mRNA\u6c34\u5e73\u3002\u6570\u636e\u8868\u793a\u6307\u5b9a\u6761\u4ef6\u4e0b\u57fa\u56e0\u8868\u8fbe\u7684\u53d8\u5316\u500d\u6570\uff0c\u76f8\u5bf9\u4e8e\u8868\u8fbe\u975e\u9776\u5411\u548cAAVS1 sgRNAs\u7684MDA-MB-436\u7ec6\u80de\u3002\u67f1\u72b6\u56fe\u4ee3\u8868\u72ec\u7acb\u751f\u7269\u5b66\u91cd\u590d\u5b9e\u9a8c\u7684\u5e73\u5747\u503c\u00b1SEM\uff08\u70b9\u72b6\u56fe\uff09\u3002p\u503c\u901a\u8fc7\u5355\u56e0\u7d20\u65b9\u5dee\u5206\u6790\uff08one-way ANOVA\uff09\u8ba1\u7b97\u3002<\/p>\n

(J) \u514d\u75ab\u5370\u8ff9\u56fe\u663e\u793a\u4e86\u8868\u8fbe\u6307\u5b9asgRNAs\u7684MDA-MB-436-CRISPRi\u7ec6\u80de\u4e2dJUN\u3001PD-L1\u548ctubulin\u7684\u6c34\u5e73\u3002<\/p>\n<\/section>\n<\/section>\n<\/section>\n

\n
\n
\n
<\/section>\n<\/section>\n
\n

\u56fe6\uff1a\u9488\u5bf9SMARCAL1\u7f3a\u5931\u7684\u764c\u7ec6\u80de\u7684\u6297\u80bf\u7624\u514d\u75ab\u53cd\u5e94\u5206\u6790<\/strong><\/p>\n

(A) C57BL\/6\u5c0f\u9f20\u76ae\u4e0b\u63a5\u79cd\u542b\u91cd\u7ec4Smarcal1 cDNA\u6216\u7a7a\u8f7d\u4f53\uff08EV\uff09\u7684B16\/F10 Smarcal1-KO\u7ec6\u80de\u540e\u7684\u80bf\u7624\u4f53\u79ef\u5206\u6790\u3002\u56fe\u8868\u4ee3\u8868\u4e09\u4e2a\u72ec\u7acb\u5b9e\u9a8c\u7684\u7ed3\u679c\uff0c\u5e76\u663e\u793a\u6bcf\u7ec4\u5c0f\u9f20\u7684\u5e73\u5747\u503c\u00b1SEM\u3002p\u503c\u901a\u8fc7\u672a\u914d\u5bf9t\u68c0\u9a8c\u8ba1\u7b97\u3002<\/p>\n

(B) \u4e0a\u8ff0C57BL\/6\u5c0f\u9f20\u7684\u751f\u5b58\u5206\u6790\u3002p\u503c\u901a\u8fc7\u5bf9\u6570\u79e9\u68c0\u9a8c\u8ba1\u7b97\u3002<\/p>\n

(C) C57BL\/6\u5c0f\u9f20\u76ae\u4e0b\u63a5\u79cd\u542b\u91cd\u7ec4Smarcal1 cDNA\u7684B16\/F10 Smarcal1-KO\u7ec6\u80de\uff0c\u5e76\u4f34\u6709\u6216\u4e0d\u4f34\u6709Cgas\u57fa\u56e0\u4e2d\u65ad\u7684\u80bf\u7624\u4f53\u79ef\u5206\u6790\u3002\u56fe\u8868\u4ee3\u8868\u4e24\u4e2a\u72ec\u7acb\u5b9e\u9a8c\u7684\u7ed3\u679c\uff0c\u5e76\u663e\u793a\u6bcf\u7ec4\u5c0f\u9f20\u7684\u5e73\u5747\u503c\u00b1SEM\u3002p\u503c\u7684\u8ba1\u7b97\u65b9\u6cd5\u540c(A)\u3002<\/p>\n

(D) \u4e0a\u8ff0C57BL\/6\u5c0f\u9f20\u7684\u751f\u5b58\u5206\u6790\u3002\u5b9e\u9a8c\u548c\u5206\u6790\u65b9\u6cd5\u540c(B)\u3002<\/p>\n

(E) C57BL\/6\u5c0f\u9f20\u63a5\u79cd\u4e0a\u8ff0(A)\u4e2d\u63cf\u8ff0\u7684B16\/F10 Smarcal1-KO\u7ec6\u80de\u540e\u80bf\u7624\u5185\u6dcb\u5df4\u7ec6\u80de\u7684\u6570\u91cf\u3002\u6bcf\u4e2a\u70b9\u4ee3\u8868\u5355\u4e2a\u80bf\u7624\u4e2d\u6bcf\u514b\u7684\u6d78\u6da6\u6dcb\u5df4\u7ec6\u80de\u6570\u91cf\u3002p\u503c\u901a\u8fc7\u672a\u914d\u5bf9t\u68c0\u9a8c\u8ba1\u7b97\u3002<\/p>\n

(F) C57BL\/6\u5c0f\u9f20\u5728\u63a5\u79cd\u4e0a\u8ff0(A)\u4e2d\u63cf\u8ff0\u7684B16\/F10 Smarcal1-KO\u7ec6\u80de\u524d\uff0c\u7ecf\u8fc7\u540c\u79cd\u578b\u5bf9\u7167\u6216\u6297\u5c0f\u9f20CD8a\u6297\u4f53\u5904\u7406\u540e\u7684\u80bf\u7624\u4f53\u79ef\u5206\u6790\u3002\u56fe\u5f62\u8868\u793a\u548c\u7edf\u8ba1\u5206\u6790\u65b9\u6cd5\u540c(A)\u3002\u8be6\u89c1\u56feS7F\u548cS7G\u3002<\/p>\n

(G) \u4e0a\u8ff0(F)\u4e2d\u63cf\u8ff0\u7684C57BL\/6\u5c0f\u9f20\u7684\u751f\u5b58\u5206\u6790\u3002\u5b9e\u9a8c\u548c\u7edf\u8ba1\u5206\u6790\u65b9\u6cd5\u540c(B)\u3002<\/p>\n

(H) (NLS)-dsRed-MDA-MB-436\u5bf9\u7167\u548cSMARCAL1-KO #1\u7ec6\u80de\uff0c\u8f6c\u5bfcPD-L1 cDNA\uff08pHAGE_PD-L1\uff09\u6216\u7a7a\u8f7d\u4f53\uff08pHAGE_EV\uff09\uff0c\u5e76\u4e0e\u6216\u4e0d\u4e0e\u4ebaCD8+ <\/sup>T\u7ec6\u80de\u5171\u5b75\u80b248\u5c0f\u65f6\uff08T2\uff09\u7684\u4ee3\u8868\u6027\u56fe\u50cf\u3002\u8be6\u89c1\u56feS8D\u3002<\/p>\n

(I) \u5728\u4e0e\u6d3b\u5316\u7684CD8+ <\/sup>T\u7ec6\u80de\u5171\u5b75\u80b2\u540eT2\u65f6\u523b\uff0c\u4e0a\u8ff0(H)\u4e2d\u63cf\u8ff0\u7684\u80bf\u7624\u7ec6\u80de\u7684\u751f\u957f\u91cf\u5316\u3002\u6761\u5f62\u56fe\u4ee3\u8868\u5728CD8+ <\/sup>T\u7ec6\u80de\u5b58\u5728\u65f6\uff0c\u8f6c\u5bfc\u4e86\u6307\u5b9a\u8d28\u7c92\u7684(NLS)-dsRed-MDA-MB-436\u5bf9\u7167\u7ec6\u80de\u548cSMARCAL1-KO #1\u7ec6\u80de\u76f8\u5bf9\u4e8e\u6ca1\u6709CD8+ <\/sup>T\u7ec6\u80de\u65f6\u7684\u589e\u6b96\u7387\u3002\u67f1\u72b6\u56fe\u4ee3\u8868\u4e09\u6b21\u91cd\u590d\u5b9e\u9a8c\u7684\u5e73\u5747\u503c\u00b1SD\u3002p\u503c\u901a\u8fc7\u4e24\u56e0\u7d20\u65b9\u5dee\u5206\u6790\uff08two-way ANOVA\uff09\u8ba1\u7b97\u3002<\/p>\n<\/section>\n<\/section>\n<\/section>\n

\n
\n
\n
<\/section>\n<\/section>\n
\n

\u56fe7\uff1a\u5728\u643a\u5e26Smarcal1\u7f3a\u5931\u80bf\u7624\u7684\u5c0f\u9f20\u4e2d\u8fdb\u884c\u514d\u75ab\u68c0\u67e5\u70b9\u963b\u65ad\u6cbb\u7597\u7684\u6548\u679c\uff0c\u4ee5\u53ca\u4f4eSMARCAL1\u8868\u8fbe\u764c\u75c7\u60a3\u8005\u7684\u4e34\u5e8a\u7ed3\u679c\u5206\u6790<\/strong><\/p>\n

(A) \u5728\u6ce8\u5c04\u4e86\u91cd\u7ec4Smarcal1 cDNA\u6216\u7a7a\u8f7d\u4f53\uff08EV\uff09\u7684B16\/F10 Smarcal1-KO\u7ec6\u80de\u7684\u5c0f\u9f20\u4e2d\u8fdb\u884c\u514d\u75ab\u68c0\u67e5\u70b9\u963b\u65ad\uff08ICB\uff09\u6cbb\u7597\u7684\u793a\u610f\u56fe\u3002<\/p>\n

(B) \u5728C57BL\/6\u5c0f\u9f20\u76ae\u4e0b\u6ce8\u5c04\u5982(A)\u6240\u8ff0\u91cd\u7ec4\u7684B16\/F10 Smarcal1-KO\u7ec6\u80de\uff0c\u5e76\u968f\u540e\u7528\u540c\u578b\u5bf9\u7167\u6216\u6297\u5c0f\u9f20CTLA-4\u52a0\u6297\u5c0f\u9f20PD-L1\u6297\u4f53\u8fdb\u884c\u6cbb\u7597\u7684\u80bf\u7624\u4f53\u79ef\u5206\u6790\u3002\u6570\u636e\u4ee3\u8868\u6bcf\u7ec4\u5c0f\u9f20\u4e2a\u4f53\u7684\u5e73\u5747\u503c\u00b1SEM\u3002p\u503c\u901a\u8fc7\u591a\u4e2a\u672a\u914d\u5bf9t\u68c0\u9a8c\u8ba1\u7b97\u3002<\/p>\n

(C) \u5bf9(B)\u4e2d\u63cf\u8ff0\u7684C57BL\/6\u5c0f\u9f20\u8fdb\u884c\u7684\u751f\u5b58\u5206\u6790\u3002p\u503c\u901a\u8fc7log rank\u68c0\u9a8c\u8ba1\u7b97\u3002<\/p>\n

(D) \u5728TCGA\u60a3\u8005\u7684\u80bf\u7624\u53ca\u5176\u76f8\u5e94\u6b63\u5e38\u7ec4\u7ec7\u4e2d\u5206\u6790\u6307\u5b9a\u764c\u75c7\u7c7b\u578b\u7684SMARCAL1\u8868\u8fbe\u3002p\u503c\u901a\u8fc7\u4e0d\u7b49\u65b9\u5deet\u68c0\u9a8c\u8ba1\u7b97\u3002CPM\u4ee3\u8868\u6bcf\u767e\u4e07\u8ba1\u6570\u3002<\/p>\n

(E) \u5728\u6307\u5b9a\u7684\u6807\u5fd7\u57fa\u56e0\u96c6\uff08MSigDB\uff09\u3001PD-L1\u8868\u8fbe\u548c\u767d\u7ec6\u80de\u5f97\u5206\u6bd4\u7387\u4e2d\uff0c\u9488\u5bf9SMARCAL1\u4f4e\u8868\u8fbe\u4e0eSMARCAL1\u9ad8\u8868\u8fbe\u764c\u75c7\u60a3\u8005\u7684\u80bf\u7624\u80cc\u666f\u7279\u5f02\u6027\u5dee\u5f02\u5206\u6790\u3002<\/p>\n

(F) \u5bf9\u4e8e\u6307\u5b9a\u7684TCGA\u80bf\u7624\u7c7b\u578b\uff0c\u708e\u75c7\u53cd\u5e94\u901a\u8def\u7684\u6807\u51c6\u5316\u5bcc\u96c6\u5f97\u5206\uff08NES\uff09\u4e0e\u767d\u7ec6\u80de\u5f97\u5206\u6bd4\u7387\u4e4b\u95f4\u7684\u76ae\u5c14\u900a\u76f8\u5173\u6027\u5206\u6790\u3002<\/p>\n

(G) \u5728\u63a5\u53d7\u6297PD-1\u68c0\u67e5\u70b9\u6291\u5236\u5242\u6cbb\u7597\u524d\uff0c\u975e\u5e94\u7b54\u7ec4\u548c\u5e94\u7b54\u7ec4\u60a3\u8005\u7684SMARCAL1\u6c34\u5e73\uff0c\u6765\u6e90\u4e8e\u53c2\u8003\u6570\u636e\u96c6\u3002p\u503c\u901a\u8fc7\u4e0d\u7b49\u65b9\u5deet\u68c0\u9a8c\u8ba1\u7b97\u3002FPKM\u4ee3\u8868\u6bcf\u767e\u4e07\u6620\u5c04\u8bfb\u6570\u6bcf\u5343\u78b1\u57fa\u8f6c\u5f55\u7247\u6bb5\u7684\u7247\u6bb5\u6570\u3002<\/p>\n

(H) SMARCAL1\u5728\u8c03\u8282\u80bf\u7624\u5bf9\u5bbf\u4e3b\u514d\u75ab\u53cd\u5e94\u53caPD-L1\u4ecb\u5bfc\u7684\u514d\u75ab\u68c0\u67e5\u70b9\u53cd\u5e94\u4e2d\u7684\u53cc\u91cd\u4f5c\u7528\u6a21\u578b\u3002<\/p>\n<\/section>\n<\/section>\n<\/section>\n

\n
\n
\n

OncoLab\u516c\u4f17\u53f7\u5df2\u589e\u52a0\u671f\u520a\u67e5\u8be2\u529f\u80fd<\/span><\/strong>\uff0cSCI\u671f\u520a<\/strong><\/span>\u53ef\u67e5\u8be2\u671f\u520a\u540d\u79f0\u7f29\u5199\u3001ISSN\u520a\u53f7\u3001\u8fd1\u4e94\u5e74\u5f71\u54cd\u56e0\u5b50<\/strong>\u3001\u6700\u65b0WOS\u7684JCR\u5206\u533a<\/strong>\u3001\u6700\u65b0\u4e2d\u79d1\u9662\u5206\u533a<\/strong>\u4ee5\u53ca\u4e2d\u79d1\u9662\u671f\u520a\u9884\u8b66\u4fe1\u606f<\/strong>\uff1b<\/p>\n

\u4e2d\u6587\u671f\u520a<\/span><\/strong>\u53ef\u68c0\u7d22CSCD\u6838\u5fc3<\/strong>\u3001\u5317\u5927\u4e2d\u6587\u6838\u5fc3<\/strong>\u3001\u79d1\u6280\u6838\u5fc3<\/strong>\u6536\u5f55\u60c5\u51b5\uff1b<\/p>\n

\u5728\u516c\u4f17\u53f7\u5bf9\u8bdd\u6846\u53d1\u9001\u6742\u5fd7\u540d\u79f0<\/span><\/strong>\u5373\u53ef\u5feb\u901f\u68c0\u7d22\uff0c\u652f\u6301\u6a21\u7cca\u68c0\u7d22\uff0c\u6b22\u8fce\u4f7f\u7528\uff01<\/p>\n<\/section>\n<\/section>\n<\/section>\n<\/section>\n

\u2014 THE  END \u2014<\/span><\/section>\n
\u6765\u6e90 | Cell<\/span><\/span><\/section>\n
\u7b5b\u9009\u6574\u7406 | \u738b\u5764<\/span><\/span><\/span><\/section>\n
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\u672c\u7bc7\u6587\u7ae0\u6765\u6e90\u4e8e\u5fae\u4fe1\u516c\u4f17\u53f7: OncoLab <\/p>\n<\/blockquote>\n<\/div>\n","protected":false},"excerpt":{"rendered":"

\u6742\u5fd7\u540d\u79f0\uff1aCell \u53d1\u8868\u65e5\u671f\uff1a2024.01.25 DOI\uff1a10.1016\/j.cell.2024.01.00…<\/p>\n","protected":false},"author":1,"featured_media":3381,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":[],"categories":[63],"tags":[],"_links":{"self":[{"href":"http:\/\/oncolab.cn\/index.php\/wp-json\/wp\/v2\/posts\/3390"}],"collection":[{"href":"http:\/\/oncolab.cn\/index.php\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"http:\/\/oncolab.cn\/index.php\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"http:\/\/oncolab.cn\/index.php\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"http:\/\/oncolab.cn\/index.php\/wp-json\/wp\/v2\/comments?post=3390"}],"version-history":[{"count":0,"href":"http:\/\/oncolab.cn\/index.php\/wp-json\/wp\/v2\/posts\/3390\/revisions"}],"wp:featuredmedia":[{"embeddable":true,"href":"http:\/\/oncolab.cn\/index.php\/wp-json\/wp\/v2\/media\/3381"}],"wp:attachment":[{"href":"http:\/\/oncolab.cn\/index.php\/wp-json\/wp\/v2\/media?parent=3390"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"http:\/\/oncolab.cn\/index.php\/wp-json\/wp\/v2\/categories?post=3390"},{"taxonomy":"post_tag","embeddable":true,"href":"http:\/\/oncolab.cn\/index.php\/wp-json\/wp\/v2\/tags?post=3390"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}