Transcriptional changes and the role of ONECUT1 in hPSC pancreatic differentiation.
Transcriptional changes and the role of ONECUT1 in hPSC pancreatic differentiation.
复制标题
DOI：
10.1038/s42003-021-02818-3
复制
发表时间：
2021-11-17
影响因子：
5.9
通讯作者：
Costa IG
中科院分区：
文献类型：
--
作者：
Heller S;Li Z;Lin Q;Geusz R;Breunig M;Hohwieler M;Zhang X;Nair GG;Seufferlein T;Hebrok M;Sander M;Julier C;Kleger A;Costa IG
胰腺发育过程中的细胞类型特化受到转录和表观遗传网络的严格控制。然而，大多数转录因子的确切作用仅在小鼠中描述。为了将这样的概念传达给人胰腺发育，可以采用替代的模型系统，例如人多能干细胞的胰腺体外分化。在这里，我们分析了阶段特异性RNA，ChIP和ATAC测序数据，以剖析胰腺发育过程中的转录和调控机制。人类多能干细胞胰腺分化的转录组和开放染色质图谱提供了已知胰腺转录因子的阶段特异性模式，并表明ONECUT1是胰腺祖细胞中关键的命运调节因子。此外，我们的数据表明，ONECUT1也参与了胰腺祖细胞的准备，为以后的内分泌特化。对转录和调控回路的解剖揭示了ONECUT1在这种网络中的重要作用，并将作为研究人类发育和疾病的资源。Heller等人分析了来自分化为胰腺祖细胞的人PSC的转录组和表观遗传数据集，以阐明胰腺发育背后的调控机制。作者报告说，转录因子ONECUT1在胰腺发育中特异性表达，并与内分泌特化过程中的其他关键转录因子（如FOXA 2，GATA 6，PDX 1）相关。
Cell type specification during pancreatic development is tightly controlled by a transcriptional and epigenetic network. The precise role of most transcription factors, however, has been only described in mice. To convey such concepts to human pancreatic development, alternative model systems such as pancreatic in vitro differentiation of human pluripotent stem cells can be employed. Here, we analyzed stage-specific RNA-, ChIP-, and ATAC-sequencing data to dissect transcriptional and regulatory mechanisms during pancreatic development. Transcriptome and open chromatin maps of pancreatic differentiation from human pluripotent stem cells provide a stage-specific pattern of known pancreatic transcription factors and indicate ONECUT1 as a crucial fate regulator in pancreas progenitors. Moreover, our data suggest that ONECUT1 is also involved in preparing pancreatic progenitors for later endocrine specification. The dissection of the transcriptional and regulatory circuitry revealed an important role for ONECUT1 within such network and will serve as resource to study human development and disease. Heller et al analyze transcriptomic and epigenetic datasets from human PSCs differentiating into pancreatic progenitors to elucidate the regulatory mechanisms behind pancreatic development. The authors report that the transcription factor ONECUT1 is expressed specifically in pancreatic development and associates with other key TFs (such as FOXA2, GATA6, PDX1) during endocrine specification.
登录
查看更多内容
影响因子：
8.1
作者：
Bastidas-Ponce A;Roscioni SS;Burtscher I;Bader E;Sterr M;Bakhti M;Lickert H
通讯作者：
Lickert H
影响因子：
16
作者：
Calo, Eliezer;Wysocka, Joanna
通讯作者：
Wysocka, Joanna
影响因子：
64.8
作者：
Heintzman, Nathaniel D.;Hon, Gary C.;Hawkins, R. David;Kheradpour, Pouya;Stark, Alexander;Harp, Lindsey F.;Ye, Zhen;Lee, Leonard K.;Stuart, Rhona K.;Ching, Christina W.;Ching, Keith A.;Antosiewicz-Bourget, Jessica E.;Liu, Hui;Zhang, Xinmin;Green, Roland D.;Lobanenkov, Victor V.;Stewart, Ron;Thomson, James A.;Crawford, Gregory E.;Kellis, Manolis;Ren, Bing
通讯作者：
Ren, Bing
影响因子：
21.3
作者：
通讯作者：
--
影响因子：
14.9
作者：
Chen J;Bardes EE;Aronow BJ;Jegga AG
通讯作者：
Jegga AG