Laser Capture and Deep Sequencing Reveals the Transcriptomic Programmes Regulating the Onset of Pancreas and Liver Differentiation in Human Embryos.
Laser Capture and Deep Sequencing Reveals the Transcriptomic Programmes Regulating the Onset of Pancreas and Liver Differentiation in Human Embryos.
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DOI：
10.1016/j.stemcr.2017.09.018
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发表时间：
2017-11-14
影响因子：
5.9
通讯作者：
Hanley NA
中科院分区：
文献类型：
--
作者：
Jennings RE;Berry AA;Gerrard DT;Wearne SJ;Strutt J;Withey S;Chhatriwala M;Piper Hanley K;Vallier L;Bobola N;Hanley NA
为了探究胰腺和肝脏在人类器官形成的最早阶段的替代命运，我们开发了激光捕获、RNA扩增和深度测序的计算分析。胰腺富集的基因表达在人类和小鼠之间比在肝脏中更不保守。背侧胰腺芽富含Notch、Wnt、BMP和FGF信号传导的组分，几乎所有已知引起胰腺发育不全或发育不全的基因，以及超过30种未探索的转录因子。与肝脏中的EP300、HNF4A和FOXA家族成员相比，SOX9和RORA被插补为胰腺中的关键调节因子。分析表明，目前在体外人类干细胞分化遵循背侧而不是腹侧胰腺程序，并指出了肝分化的其他因素。总之，我们提供了调节人类肝脏和胰腺发育开始的转录密码，以促进干细胞研究和临床解释，而无需种间外推。人类肝脏和胰腺发育开始时的转录组学特征人类和小鼠之间胰腺富集基因表达的有限保守人类PSC方案意味着背侧而不是腹侧胰腺程序通过差异分析估算的新胰腺转录因子Jennings et al.在植入后非常早期的人类胚胎中，在肝脏和胰腺发育的开始时呈现第一个转录组。通过计算分析，他们估算了每个器官中的调控特征，包括胰腺中的新转录因子和人类多能干细胞分化的新指导。
To interrogate the alternative fates of pancreas and liver in the earliest stages of human organogenesis, we developed laser capture, RNA amplification, and computational analysis of deep sequencing. Pancreas-enriched gene expression was less conserved between human and mouse than for liver. The dorsal pancreatic bud was enriched for components of Notch, Wnt, BMP, and FGF signaling, almost all genes known to cause pancreatic agenesis or hypoplasia, and over 30 unexplored transcription factors. SOX9 and RORA were imputed as key regulators in pancreas compared with EP300, HNF4A, and FOXA family members in liver. Analyses implied that current in vitro human stem cell differentiation follows a dorsal rather than a ventral pancreatic program and pointed to additional factors for hepatic differentiation. In summary, we provide the transcriptional codes regulating the start of human liver and pancreas development to facilitate stem cell research and clinical interpretation without inter-species extrapolation. Transcriptomic signatures at the inception of human liver and pancreas development Limited conservation of pancreas-enriched gene expression between human and mouse Human PSC protocols imply a dorsal rather than a ventral pancreatic program New pancreatic transcription factors imputed by differential analysis Jennings et al. present the first transcriptomes at the inception of liver and pancreas development in very early post-implantation human embryos. By computational analysis, they impute regulatory signatures in each organ, including new transcription factors in pancreas and new guidance for human pluripotent stem cell differentiation.
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影响因子：
21.3
作者：
通讯作者：
--
影响因子：
7
作者：
Harrow J;Frankish A;Gonzalez JM;Tapanari E;Diekhans M;Kokocinski F;Aken BL;Barrell D;Zadissa A;Searle S;Barnes I;Bignell A;Boychenko V;Hunt T;Kay M;Mukherjee G;Rajan J;Despacio-Reyes G;Saunders G;Steward C;Harte R;Lin M;Howald C;Tanzer A;Derrien T;Chrast J;Walters N;Balasubramanian S;Pei B;Tress M;Rodriguez JM;Ezkurdia I;van Baren J;Brent M;Haussler D;Kellis M;Valencia A;Reymond A;Gerstein M;Guigó R;Hubbard TJ
通讯作者：
Hubbard TJ
影响因子：
46.9
作者：
Rezania, Alireza;Bruin, Jennifer E.;Kieffer, Timothy J.
通讯作者：
Kieffer, Timothy J.
影响因子：
14.9
作者：
McCarthy DJ;Chen Y;Smyth GK
通讯作者：
Smyth GK
影响因子：
2.6
作者：
Piper, K;Ball, SG;Hanley, NA
通讯作者：
Hanley, NA