A comparative study of endoderm differentiation in humans and chimpanzees.
A comparative study of endoderm differentiation in humans and chimpanzees.
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DOI：
10.1186/s13059-018-1490-5
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发表时间：
2018-10-15
期刊：
影响因子：
12.3
通讯作者：
Pavlovic BJ
中科院分区：
文献类型：
--
作者：
Blake LE;Thomas SM;Blischak JD;Hsiao CJ;Chavarria C;Myrthil M;Gilad Y;Pavlovic BJ
人们对早期人类发展中形成调控框架的进化力量非常感兴趣。由于难以获得相关的生物样本，这一领域的进展缓慢。诱导多能干细胞（iPSCs）可以提供建立早期人类和非人灵长类动物发育阶段的体外模型的能力。使用来自人类和黑猩猩的匹配iPSC面板，我们通过四天的时间过程将iPSC分化为初级条、内胚层祖细胞和最终内胚层，比较表征了基因调控变化。正如预期的那样，我们发现分化阶段是基因表达水平变化的主要驱动因素，其次是物种。我们确定了人类和黑猩猩在每个分化阶段的数千个差异表达基因。然而，当我们在整个时间过程中考虑基因特异性动态调控轨迹时，我们发现至少75%的基因，包括几乎所有已知的内胚层发育标记，在这两个物种中具有相似的轨迹。有趣的是，与iPSCs相比，我们观察到原始条纹样品中基因表达水平的种内和种间变异显著减少，内胚层祖细胞的调节变异恢复。基因表达水平变异在特定发育阶段的减少，与时间基因调控的总体高度保守相结合，与保守发育过程的动力学一致。本文的在线版本（10.1186/s13059-018-1490-5）包含补充资料，仅供授权用户使用。
There is substantial interest in the evolutionary forces that shaped the regulatory framework in early human development. Progress in this area has been slow because it is difficult to obtain relevant biological samples. Induced pluripotent stem cells (iPSCs) may provide the ability to establish in vitro models of early human and non-human primate developmental stages. Using matched iPSC panels from humans and chimpanzees, we comparatively characterize gene regulatory changes through a four-day time course differentiation of iPSCs into primary streak, endoderm progenitors, and definitive endoderm. As might be expected, we find that differentiation stage is the major driver of variation in gene expression levels, followed by species. We identify thousands of differentially expressed genes between humans and chimpanzees in each differentiation stage. Yet, when we consider gene-specific dynamic regulatory trajectories throughout the time course, we find that at least 75% of genes, including nearly all known endoderm developmental markers, have similar trajectories in the two species. Interestingly, we observe a marked reduction of both intra- and inter-species variation in gene expression levels in primitive streak samples compared to the iPSCs, with a recovery of regulatory variation in endoderm progenitors. The reduction of variation in gene expression levels at a specific developmental stage, paired with overall high degree of conservation of temporal gene regulation, is consistent with the dynamics of a conserved developmental process. The online version of this article (10.1186/s13059-018-1490-5) contains supplementary material, which is available to authorized users.
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遗传对人体组织基因表达的影响。
影响因子：
64.8
作者：
GTEx Consortium;Laboratory, Data Analysis &Coordinating Center (LDACC)—Analysis Working Group;Statistical Methods groups—Analysis Working Group;Enhancing GTEx (eGTEx) groups;NIH Common Fund;NIH/NCI;NIH/NHGRI;NIH/NIMH;NIH/NIDA;Biospecimen Collection Source Site—NDRI;Biospecimen Collection Source Site—RPCI;Biospecimen Core Resource—VARI;Brain Bank Repository—University of Miami Brain Endowment Bank;Leidos Biomedical—Project Management;ELSI Study;Genome Browser Data Integration &Visualization—EBI;Genome Browser Data Integration &Visualization—UCSC Genomics Institute, University of California Santa Cruz;Lead analysts:;Laboratory, Data Analysis &Coordinating Center (LDACC):;NIH program management:;Biospecimen collection:;Pathology:;eQTL manuscript working group:;Battle A;Brown CD;Engelhardt BE;Montgomery SB
通讯作者：
Montgomery SB
影响因子：
7
作者：
Blekhman, Ran;Marioni, John C.;Gilad, Yoav
通讯作者：
Gilad, Yoav
影响因子：
5.8
作者：
Ballman, KV;Grill, DE;Therneau, TM
通讯作者：
Therneau, TM
影响因子：
5.8
作者：
Kembel, Steven W.;Cowan, Peter D.;Webb, Campbell O.
通讯作者：
Webb, Campbell O.
DOI：
10.1242/dev.014357
发表时间：
2008-02
期刊：
Development (Cambridge, England)
影响因子：
--
作者：
Arnold SJ;Hofmann UK;Bikoff EK;Robertson EJ
通讯作者：
Robertson EJ