Differentiation of Human Pluripotent Stem Cells into Colonic Organoids via Transient Activation of BMP Signaling.
Differentiation of Human Pluripotent Stem Cells into Colonic Organoids via Transient Activation of BMP Signaling.
复制标题
DOI：
10.1016/j.stem.2017.05.020
复制
发表时间：
2017-07-06
期刊：
影响因子：
23.9
通讯作者：
Wells JM
中科院分区：
文献类型：
--
作者：
Múnera JO;Sundaram N;Rankin SA;Hill D;Watson C;Mahe M;Vallance JE;Shroyer NF;Sinagoga KL;Zarzoso-Lacoste A;Hudson JR;Howell JC;Chatuvedi P;Spence JR;Shannon JM;Zorn AM;Helmrath MA;Wells JM
从人多能干细胞（hPSC）分化的胃和小肠类器官彻底改变了胃肠道发育和疾病的研究。然而，远端肠道组织如盲肠和结肠，已经证明在体外获得更具挑战性。在这里，我们报告了人类结肠类器官（HCO）从hPSC的分化。我们发现BMP信号传导是在发育和出生后肠上皮中建立后部Satb2+结构域所必需的。BMP信号传导的短暂激活足以激活后HOX密码并将人PSC衍生的肠管培养物引导至HCO。在体外，HCOs表达结肠标记物并含有结肠特异性细胞群。在移植到小鼠中后，HCO经历形态发生和成熟以形成表现出人结肠的分子、细胞和形态学特性的组织。这些数据共同显示了人类后肠形成HCO的BMP依赖性模式，这对于研究包括结肠炎和结肠癌在内的疾病将是有价值的。
Gastric and small intestinal organoids differentiated from human pluripotent stem cells (hPSCs) have revolutionized the study of gastrointestinal development and disease. Distal gut tissues such as cecum and colon, however, have proven considerably more challenging to derive in vitro. Here we report the differentiation of human colonic organoids (HCOs) from hPSCs. We found BMP signaling is required to establish a posterior Satb2+ domain in developing and postnatal intestinal epithelium. Brief activation of BMP signaling is sufficient to activate a posterior HOX code and direct human PSC-derived gut tube cultures into HCOs. In vitro, HCOs express colonic markers and contained colon-specific cell populations. Following transplantation into mice, HCOs undergo morphogenesis and maturation to form tissue that exhibits molecular, cellular, and morphologic properties of human colon. Together these data show BMP-dependent patterning of human hindgut into HCOs, which will be valuable for studying diseases including colitis and colon cancer.
登录
查看更多内容
影响因子：
4.6
作者：
Georgas, Kylie M.;Armstrong, Jane;Mendelsohn, Cathy
通讯作者：
Mendelsohn, Cathy
影响因子：
2.7
作者：
Beuling, Eva;Bosse, Tjalling;aan de Kerk, Daniel J.;Piaseckyj, Christina M.;Fujiwara, Yuko;Katz, Samuel G.;Orkin, Stuart H.;Grand, Richard J.;Krasinski, Stephen D.
通讯作者：
Krasinski, Stephen D.
影响因子：
5.4
作者：
Holland PW;Booth HA;Bruford EA
通讯作者：
Bruford EA
影响因子：
3.4
作者：
Gyorgy, Andrea B.;Szemes, Marianna;Agoston, Denes V.
通讯作者：
Agoston, Denes V.
DOI：
10.1083/jcb.201302049
发表时间：
2013-06-10
期刊：
The Journal of cell biology
影响因子：
--
作者：
Guo Z;Driver I;Ohlstein B
通讯作者：
Ohlstein B