汕尾缺春饰网络科技_最大小区重编程“地图”上行线

????本文来自Bioart(ID:Biogossip),作者:Yusha,主编:哈萨克。,2012年诺贝尔生理学或医学奖授予日本科学家Shinya Yamanaka和英国发展生物学家John Gurdon,因为他们在核重编程方面的杰出贡献[1]。2006年,Yamanaka成功地通过逆转录病毒将4种转录因子oct3/4、sox2、c-myc和klf4转化为小鼠胚胎成纤维细胞(mef)和尾端成纤维细胞(ttf),并将这两种细胞转化为诱导多能干细胞(ipsc)[2]。随后,Yamazawa等人实现了人皮肤成纤维细胞(hdf)重新编程为ipsc,并诱导ipsc在体外分化为神经元和心肌细胞[3,4]。目前,人ipsc可以在体外培养并分化为其他功能性细胞类型,为老年性黄斑变性等疾病提供“细胞疗法”[5]。,在试图将ipsc应用于临床治疗的同时,科学家们不断探索细胞重新编程本身的奥秘:成年细胞如何转化为多能干细胞?在此过程中,细胞经历了什么样的谱系变化和细胞命运决定?,2019年2月7日,《细胞》杂志发表了一篇题为《单细胞基因表达的最佳运输分析识别重编程中的发展轨迹》的文章,由布罗德研究所所长兼创始人埃里克·S·兰德教授、麻省理工学院阿维夫·雷格夫教授和舒健博士合着。大规模单细胞RNA测序的结果绘制了从小鼠胚胎成纤维细胞到ipsc重编程的“细胞图”。这种开发方法也可以应用于其他复杂的生物过程和系统。,本文合着者、合着者舒健博士在小鼠成纤维细胞重新编程为ipsc进行单细胞RNA测序的过程中,每6-12小时采集一次样本,持续18天。他们收集了超过315000个单细胞RNA测序的数据,这是迄今为止细胞重新编程领域最大的单细胞RNA测序研究。研究人员建立了如此庞大和时间密集的数据集,因为单细胞RNA测序只能为我们提供特定条件下细胞的表达谱,而不能跟踪和分析细胞的状态。,资料来源:Schiebinger等人,2019年。图2A,在获得离散单细胞RNA的高密度测序结果后,研究人员希望将这些快照数据拼接成“电影”,以准确跟踪细胞从一种状态到另一种状态的路径。然而,这个过程并不容易。1957年,英国生物学家沃丁顿将细胞分化比作在有山脊和山谷的滑雪斜坡上滚动的大理石,称之为“表观遗传景观”[6](下图)。,照片来源:,在这个过程中,岩石滚下不同的轨道,落入不同的山谷,就像不同的细胞命运。然而,沃丁顿的类比并没有追踪到一组细胞在分化过程中可能采取的路径。我们不知道哪些岩石最终会掉入不同的山谷。那么,如何将斜坡顶部与底部的岩石连接起来,预测岩石下落的路径呢?本文的研究者采用最优运输(OT),建立了瓦丁顿OT的基本框架(上图)。“最优传递理论”是法国数学家蒙在20世纪80年代首次提出的,拿破仑用它来计算防御工事期间士兵的土壤运动。通过将不同时间点的细胞类型和细胞分布联系起来,研究人员使用沃丁顿OT追踪从成纤维细胞到ipsc重编程的细胞变化。,他们发现,细胞重新编程具有比以前报道更广泛的发展过程和状态变化。在重编程开始时,细胞开始分化为两种主要类型:基质细胞和间质-上皮转变,产生类似于ipsc、神经和胎盘细胞的细胞类型。,此外,研究人员发现,早期的细胞命运并不一定是固定的:一些在主要人群中开始发育的细胞后来迁移到另一种细胞类型(结果与去年早些时候发表在《科学》上的几个单细胞测序研究的结果相似)。Waddington OT还确定了不同亚细胞类型在重编程过程中出现和消失的阶段,甚至发现了一些细胞类型的基因组畸变。最后,利用Waddington OT的预测,研究人员发现转录因子obox6和细胞因子gdf9可以提高产生ipsc的效率,这表明该框架可以为进一步改进细胞重编程提供有力的帮助。,通过绘制细胞重编程的“图谱”,可以跟踪细胞发育的时间轨迹,更准确、直观地了解基因表达。据报道,布罗德研究所的研究团队正在向学术界提供免费数据,包括可下载的交互式沃丁顿OT软件。,链接到原始文本:,参考文献:,〔1〕,[2]Takahashi,K.和Yamanaka,S.(2006年)。通过确定的因子从小鼠胚胎和成纤维细胞培养中诱导多能干细胞。电话:126,663-676。,[3]Takahashi,K.、Tanabe,K.、Ohnuki,M.、Narita,M.、Ichisaka,T.、Tomoda,K.和Yamanaka,S.(2007)。从成人成纤维细胞中诱导多能干细胞的因子定义。131,861-872。,[4]Yu,J.,Vodyanik,M.A.,Smuga Otto,K.,Antosiewicz Bourget,J.,Frane,J.L.,Tian,S.,Nie,J.,Jonsdottir,G.A.,Ruotti,V.,Stewart,R.等人(2007)。诱导多能干细胞来源于人类细胞。318,1917-1920年。,[5]Mandai,M.、Watanabe,A.、Kurimoto,Y.、Hirami,Y.、Morinaga,C.、Daimon,T.、Fujihara,M.、Akimaru,H.、Sakai,N.、Shibata,Y.等人(2017)。自体诱导干细胞源性视网膜细胞在新英格兰黄斑杂志3761038-1046。,[6]Goldberg,A.D.、Allis,C.D.和Bernstein,E.(2007)。表观遗传学:景观形成。手机128,635-638。,[7]Monge,G.(1781年)。我在布雷斯和雷姆布雷斯的东方。兆欧德,〔8〕,〔9〕,本文来自Bioart(ID:Biogossip),作者:Yusha,主编:哈萨克。

ben wen lai zi Bioart ID: Biogossip, zuo zhe: Yusha, zhu bian: ha sa ke., 2012 nian nuo bei er sheng li xue huo yi xue jiang shou yu ri ben ke xue jia Shinya Yamanaka he ying guo fa zhan sheng wu xue jia John Gurdon, yin wei ta men zai he chong bian cheng fang mian di jie chu gong xian 1. 2006 nian, Yamanaka cheng gong di tong guo ni zhuan lu bing du jiang 4 zhong zhuan lu yin zi oct3 4 sox2 cmyc he klf4 zhuan hua wei xiao shu pei tai cheng xian wei xi bao mef he wei duan cheng xian wei xi bao ttf, bing jiang zhe liang zhong xi bao zhuan hua wei you dao duo neng gan xi bao ipsc 2. sui hou, Yamazawa deng ren shi xian le ren pi fu cheng xian wei xi bao hdf chong xin bian cheng wei ipsc, bing you dao ipsc zai ti wai fen hua wei shen jing yuan he xin ji xi bao 3, 4. mu qian, ren ipsc ke yi zai ti wai pei yang bing fen hua wei qi ta gong neng xing xi bao lei xing, wei lao nian xing huang ban bian xing deng ji bing ti gong" xi bao liao fa" 5., zai shi tu jiang ipsc ying yong yu lin chuang zhi liao de tong shi, ke xue jia men bu duan tan suo xi bao chong xin bian cheng ben shen de ao mi: cheng nian xi bao ru he zhuan hua wei duo neng gan xi bao? zai ci guo cheng zhong, xi bao jing li le shen me yang de pu xi bian hua he xi bao ming yun jue ding?, 2019 nian 2 yue 7 ri, xi bao za zhi fa biao le yi pian ti wei dan xi bao ji yin biao da de zui jia yun shu fen xi shi bie chong bian cheng zhong de fa zhan gui ji de wen zhang, you bu luo de yan jiu suo suo zhang jian chuang shi ren ai li ke S lan de jiao shou ma sheng li gong xue yuan a wei fu lei ge fu jiao shou he shu jian bo shi he zhu. da gui mo dan xi bao RNA ce xu de jie guo hui zhi le cong xiao shu pei tai cheng xian wei xi bao dao ipsc chong bian cheng de" xi bao tu". zhe zhong kai fa fang fa ye ke yi ying yong yu qi ta fu za de sheng wu guo cheng he xi tong., ben wen he zhu zhe he zhu zhe shu jian bo shi zai xiao shu cheng xian wei xi bao chong xin bian cheng wei ipsc jin xing dan xi bao RNA ce xu de guo cheng zhong, mei 612 xiao shi cai ji yi ci yang ben, chi xu 18 tian. ta men shou ji le chao guo 315000 ge dan xi bao RNA ce xu de shu ju, zhe shi qi jin wei zhi xi bao chong xin bian cheng ling yu zui da de dan xi bao RNA ce xu yan jiu. yan jiu ren yuan jian li liao ru ci pang da he shi jian mi ji de shu ju ji, yin wei dan xi bao RNA ce xu zhi neng wei wo men ti gong te ding tiao jian xia xi bao de biao da pu, er bu neng gen zong he fen xi xi bao de zhuang tai., zi liao lai yuan: Schiebinger deng ren, 2019 nian. tu 2A, zai huo de li san dan xi bao RNA de gao mi du ce xu jie guo hou, yan jiu ren yuan xi wang jiang zhei xie kuai zhao shu ju pin jie cheng" dian ying", yi zhun que gen zong xi bao cong yi zhong zhuang tai dao ling yi zhong zhuang tai de lu jing. ran er, zhe ge guo cheng bing bu rong yi. 1957 nian, ying guo sheng wu xue jia wo ding dun jiang xi bao fen hua bi zuo zai you shan ji he shan gu de hua xue xie po shang gun dong de da li shi, cheng zhi wei" biao guan yi chuan jing guan" 6 xia tu., zhao pian lai yuan:, zai zhe ge guo cheng zhong, yan shi gun xia bu tong de gui dao, luo ru bu tong de shan gu, jiu xiang bu tong de xi bao ming yun. ran er, wo ding dun de lei bi bing mei you zhui zong dao yi zu xi bao zai fen hua guo cheng zhong ke neng cai qu de lu jing. wo men bu zhi dao nei xie yan shi zui zhong hui diao ru bu tong de shan gu. na me, ru he jiang xie po ding bu yu di bu de yan shi lian jie qi lai, yu ce yan shi xia luo de lu jing ne? ben wen de yan jiu zhe cai yong zui you yun shu OT, jian li le wa ding dun OT de ji ben kuang jia shang tu." zui you chuan di li lun" shi fa guo shu xue jia meng zai 20 shi ji 80 nian dai shou ci ti chu de, na po lun yong ta lai ji suan fang yu gong shi qi jian shi bing de tu rang yun dong. tong guo jiang bu tong shi jian dian de xi bao lei xing he xi bao fen bu lian xi qi lai, yan jiu ren yuan shi yong wo ding dun OT zhui zong cong cheng xian wei xi bao dao ipsc chong bian cheng de xi bao bian hua., ta men fa xian, xi bao chong xin bian cheng ju you bi yi qian bao dao geng guang fan de fa zhan guo cheng he zhuang tai bian hua. zai chong bian cheng kai shi shi, xi bao kai shi fen hua wei liang zhong zhu yao lei xing: ji zhi xi bao he jian zhi shang pi zhuan bian, chan sheng lei si yu ipsc shen jing he tai pan xi bao de xi bao lei xing., ci wai, yan jiu ren yuan fa xian, zao qi de xi bao ming yun bing bu yi ding shi gu ding de: yi xie zai zhu yao ren qun zhong kai shi fa yu de xi bao hou lai qian yi dao ling yi zhong xi bao lei xing jie guo yu qu nian zao xie shi hou fa biao zai ke xue shang de ji ge dan xi bao ce xu yan jiu de jie guo xiang si. Waddington OT hai que ding liao bu tong ya xi bao lei xing zai chong bian cheng guo cheng zhong chu xian he xiao shi de jie duan, shen zhi fa xian le yi xie xi bao lei xing de ji yin zu ji bian. zui hou, li yong Waddington OT de yu ce, yan jiu ren yuan fa xian zhuan lu yin zi obox6 he xi bao yin zi gdf9 ke yi ti gao chan sheng ipsc de xiao lv, zhe biao ming gai kuang jia ke yi wei jin yi bu gai jin xi bao chong bian cheng ti gong you li de bang zhu., tong guo hui zhi xi bao chong bian cheng de" tu pu", ke yi gen zong xi bao fa yu de shi jian gui ji, geng zhun que zhi guan di liao jie ji yin biao da. ju bao dao, bu luo de yan jiu suo de yan jiu tuan dui zheng zai xiang xue shu jie ti gong mian fei shu ju, bao kuo ke xia zai de jiao hu shi wo ding dun OT ruan jian., lian jie dao yuan shi wen ben:, can kao wen xian:, 1, 2 Takahashi, K. he Yamanaka, S. 2006 nian. tong guo que ding de yin zi cong xiao shu pei tai he cheng xian wei xi bao pei yang zhong you dao duo neng gan xi bao. dian hua: 126, 663676., 3 Takahashi, K. Tanabe, K. Ohnuki, M. Narita, M. Ichisaka, T. Tomoda, K. he Yamanaka, S. 2007. cong cheng ren cheng xian wei xi bao zhong you dao duo neng gan xi bao de yin zi ding yi. 131, 861872., 4 Yu, J., Vodyanik, M. A., Smuga Otto, K., Antosiewicz Bourget, J., Frane, J. L., Tian, S., Nie, J., Jonsdottir, G. A., Ruotti, V., Stewart, R. deng ren 2007. you dao duo neng gan xi bao lai yuan yu ren lei xi bao. 318, 19171920 nian., 5 Mandai, M. Watanabe, A. Kurimoto, Y. Hirami, Y. Morinaga, C. Daimon, T. Fujihara, M. Akimaru, H. Sakai, N. Shibata, Y. deng ren 2017. zi ti you dao gan xi bao yuan xing shi wang mo xi bao zai xin ying ge lan huang ban za zhi 37610381046., 6 Goldberg, A. D. Allis, C. D. he Bernstein, E. 2007. biao guan yi chuan xue: jing guan xing cheng. shou ji 128, 635638., 7 Monge, G. 1781 nian. wo zai bu lei si he lei mu bu lei si de dong fang. zhao ou de, 8, 9, ben wen lai zi Bioart ID: Biogossip, zuo zhe: Yusha, zhu bian: ha sa ke.

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