Dynamic Gene Regulatory Networks Drive Hematopoietic Specification and Differentiation.
Dynamic Gene Regulatory Networks Drive Hematopoietic Specification and Differentiation.
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DOI：
10.1016/j.devcel.2016.01.024
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发表时间：
2016-03-07
影响因子：
11.8
通讯作者：
Bonifer C
中科院分区：
文献类型：
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作者：
Goode DK;Obier N;Vijayabaskar MS;Lie-A-Ling M;Lilly AJ;Hannah R;Lichtinger M;Batta K;Florkowska M;Patel R;Challinor M;Wallace K;Gilmour J;Assi SA;Cauchy P;Hoogenkamp M;Westhead DR;Lacaud G;Kouskoff V;Göttgens B;Bonifer C
后生动物的发育涉及特定基因表达程序的连续激活和沉默，并由组织特异性转录因子编程染色质景观驱动。为了了解这一过程如何执行整个发育过程，我们从纯化的胚胎干细胞来源的细胞中产生了全球基因表达、染色质可及性、组蛋白修饰和转录因子结合数据，这些数据代表了造血指定和分化的六个顺序阶段。我们的数据揭示了驱动差异基因表达的调控元件的性质，并揭示了转录因子结合如何影响启动子的活性。我们提出了一个用于造血规范的动态核心调控网络模型，并展示了该模型在重编程实验设计中的有效性。在我们全基因组数据的推动下进行的功能研究揭示了TEAD/YAP因子在哺乳动物造血规范中的阶段特异性作用。我们的研究为研究造血提供了一个强大的资源，并展示了这些数据如何促进我们对哺乳动物发育的理解。全面基因组规模的资源用于研究胚胎血细胞规格基因组规模驱动差异基因表达的顺式元件的定义造血辅助重编程实验的基因调控网络模型分析表明TEAD因素在造血规格Goode，Obier，Vijayabaskar等人中的作用。从胚胎干细胞开始，分离处于六个不同造血细胞分化阶段的细胞，并对这一发育途径进行全面的多组学分析。这些数据确定了造血规范的调节因素，并强调了将非血细胞重新编程为血液的最低要求。
Metazoan development involves the successive activation and silencing of specific gene expression programs and is driven by tissue-specific transcription factors programming the chromatin landscape. To understand how this process executes an entire developmental pathway, we generated global gene expression, chromatin accessibility, histone modification, and transcription factor binding data from purified embryonic stem cell-derived cells representing six sequential stages of hematopoietic specification and differentiation. Our data reveal the nature of regulatory elements driving differential gene expression and inform how transcription factor binding impacts on promoter activity. We present a dynamic core regulatory network model for hematopoietic specification and demonstrate its utility for the design of reprogramming experiments. Functional studies motivated by our genome-wide data uncovered a stage-specific role for TEAD/YAP factors in mammalian hematopoietic specification. Our study presents a powerful resource for studying hematopoiesis and demonstrates how such data advance our understanding of mammalian development. Comprehensive genome-scale resource for studying embryonic blood cell specification Genome-scale definition of cis elements driving differential gene expression A gene regulatory network model for hematopoiesis aiding reprogramming experiments Analysis suggests a role for TEAD factors in hematopoietic specification Goode, Obier, Vijayabaskar et al. isolate cells at six different stages of hematopoietic differentiation, starting from embryonic stem cells, and perform a comprehensive multi-omics analysis of this developmental pathway. The data identify regulators of hematopoietic specification and highlight the minimum requirements for the reprogramming of non-blood cells to blood.