Osblr8 orchestrates intrachromosomal loop structure required for maintaining stem cell pluripotency
Osblr8 orchestrates intrachromosomal loop structure required for maintaining stem cell pluripotency
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Osblr8 协调维持干细胞多能性所需的染色体内环结构
DOI：
10.7150/ijbs.45112
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发表时间：
2020-04
影响因子：
9.2
通讯作者：
Li Wei
中科院分区：
文献类型：
--
作者：
Zhu Yanbo;Yan Zi;Du Zhonghua;Zhang Shilin;Fu Changhao;Meng Ying;Wen Xue;Wang Yizhuo;Hoffman Andrew R.;Hu Ji-Fan;Cui Jiuwei;Li Wei
诱导多能干细胞（iPSCs）是通过转录因子的混合物对体细胞进行重编程而产生的，具有无限自我更新的能力和分化成体内所有细胞类型的能力。多能干细胞可能在再生医学中具有治疗潜力，可以替代受伤组织甚至整个器官。在这项研究中，我们研究了嵌入在内源性多能基因激活所需的特定三维染色体内结构中的表观遗传因素。利用染色质RNA原位反转录测序（CRIST-seq），我们发现了一种与Oct4-Sox2结合的长链非编码RNA，称为Osblr8，它与多能状态有关。Osblr8在iPSCs和E14胚胎干细胞中高表达，但在成纤维细胞中沉默。通过使用shRNA敲除Osblr8，我们发现这种lncRNA是维持多能性所必需的。Osblr8的过表达激活了内源性干细胞核心因子基因。在机制上，Osblr8参与了染色体内环结构的形成，这是在重编程过程中激活干细胞核心因子所必需的。总之，我们已经证明了lncRNA Osblr8是多能性相关主基因启动子的染色质结构调节剂，突出了其在重编程中的关键表观遗传作用。
Induced pluripotent stem cells (iPSCs), derived from reprogramming of somatic cells by a cocktail of transcription factors, have the capacity for unlimited self-renewal and the ability to differentiate into all of cell types present in the body. iPSCs may have therapeutic potential in regenerative medicine, replacing injured tissues or even whole organs. In this study, we examine epigenetic factors embedded in the specific 3-dimensional intrachromosomal architecture required for the activation of endogenous pluripotency genes. Using chromatin RNA in situ reverse transcription sequencing (CRIST-seq), we identified an Oct4-Sox2 binding long noncoding RNA, referred as to Osblr8, that is present in association with pluripotency status. Osblr8 was highly expressed in iPSCs and E14 embryonic stem cells, but it was silenced in fibroblasts. By using shRNA to knock down Osblr8, we found that this lncRNA was required for the maintenance of pluripotency. Overexpression of Osblr8 activated endogenous stem cell core factor genes. Mechanistically, Osblr8 participated in the formation of an intrachromosomal looping structure that is required to activate stem cell core factors during reprogramming. In summary, we have demonstrated that lncRNA Osblr8 is a chromatin architecture modulator of pluripotency-associated master gene promoters, highlighting its critical epigenetic role in reprogramming.
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影响因子：
64.8
作者：
Ellis, Matthew J.;Ding, Li;Shen, Dong;Luo, Jingqin;Suman, Vera J.;Wallis, John W.;Van Tine, Brian A.;Hoog, Jeremy;Goiffon, Reece J.;Goldstein, Theodore C.;Ng, Sam;Lin, Li;Crowder, Robert;Snider, Jacqueline;Ballman, Karla;Weber, Jason;Chen, Ken;Koboldt, Daniel C.;Kandoth, Cyriac;Schierding, William S.;McMichael, Joshua F.;Miller, Christopher A.;Lu, Charles;Harris, Christopher C.;McLellan, Michael D.;Wendl, Michael C.;DeSchryver, Katherine;Allred, D. Craig;Esserman, Laura;Unzeitig, Gary;Margenthaler, Julie;Babiera, G. V.;Marcom, P. Kelly;Guenther, J. M.;Leitch, Marilyn;Hunt, Kelly;Olson, John;Tao, Yu;Maher, Christopher A.;Fulton, Lucinda L.;Fulton, Robert S.;Harrison, Michelle;Oberkfell, Ben;Du, Feiyu;Demeter, Ryan;Vickery, Tammi L.;Elhammali, Adnan;Piwnica-Worms, Helen;McDonald, Sandra;Watson, Mark;Dooling, David J.;Ota, David;Chang, Li-Wei;Bose, Ron;Ley, Timothy J.;Piwnica-Worms, David;Stuart, Joshua M.;Wilson, Richard K.;Mardis, Elaine R.
通讯作者：
Mardis, Elaine R.
影响因子：
14
作者：
Chen M;Zhang H;Wu J;Xu L;Xu D;Sun J;He Y;Zhou X;Wang Z;Wu L;Xu S;Wang J;Jiang S;Zhou X;Hoffman AR;Hu X;Hu J;Li T
通讯作者：
Li T
DOI：
10.1016/j.tig.2016.10.002
发表时间：
2016-12
期刊：
Trends in genetics : TIG
影响因子：
--
作者：
Chédin F
通讯作者：
Chédin F
IGF1R基因座内的一种新型反义长非编码RNA被印记于造血系统恶性肿瘤中
影响因子：
14.9
作者：
Sun J;Li W;Sun Y;Yu D;Wen X;Wang H;Cui J;Wang G;Hoffman AR;Hu JF
通讯作者：
Hu JF
TSIX RNA和种系因子PRDM14，链接X重新激活和干细胞再编程。
影响因子：
16
作者：
Payer B;Rosenberg M;Yamaji M;Yabuta Y;Koyanagi-Aoi M;Hayashi K;Yamanaka S;Saitou M;Lee JT
通讯作者：
Lee JT