Differential Etv2 threshold requirement for endothelial and erythropoietic development.
Differential Etv2 threshold requirement for endothelial and erythropoietic development.
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DOI：
10.1016/j.celrep.2022.110881
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发表时间：
2022-05-31
期刊：
影响因子：
8.8
通讯作者：
Black, Brian L.
中科院分区：
文献类型：
--
作者：
Sinha, Tanvi;van Bueren, Kelly Lammerts;Dickel, Diane E.;Zlatanova, Ivana;Thomas, Reuben;Lizama, Carlos O.;Xu, Shan-Mei;Zovein, Ann C.;Ikegami, Kohta;Moskowitz, Ivan P.;Pollard, Katherine S.;Pennacchio, Len A.;Black, Brian L.
内皮细胞和红细胞生成谱系来自共同的发育祖细胞。Etv2是两种谱系发育所需的主要转录调节因子。然而，Etv2启动内皮细胞和红细胞生成特化的基因调控网络（GRNs）的机制以及这两个GRNs如何在Etv2下游发散仍然不完全清楚。在这里，通过分析一个亚型Etv2突变体，我们证明了不同的阈值要求启动下游GRNs内皮细胞和红细胞生成的发展。我们表明，Etv2功能直接在一个连贯的前馈转录网络血管内皮的发展，和低水平的Etv2表达是足以诱导和维持内皮GRN。相反，Etv2通过激活Tal 1间接诱导红细胞生成GRN，这需要Etv2的显著更高阈值来启动和维持红细胞生成发育。这些结果提供了重要的机制洞察内皮细胞和红细胞生成谱系的分歧。Sinha等人证明了主调节转录因子Etv2直接调节小鼠胚胎内皮基因调节网络（GRN）。相反，Etv2通过bHLH转录因子Tal 1间接调节红细胞生成GRN，使红细胞生成比血管生成对减少Etv2基因剂量更敏感。
Endothelial and erythropoietic lineages arise from a common developmental progenitor. Etv2 is a master transcriptional regulator required for the development of both lineages. However, the mechanisms through which Etv2 initiates the gene-regulatory networks (GRNs) for endothelial and erythropoietic specification and how the two GRNs diverge downstream of Etv2 remain incompletely understood. Here, by analyzing a hypomorphic Etv2 mutant, we demonstrate different threshold requirements for initiation of the downstream GRNs for endothelial and erythropoietic development. We show that Etv2 functions directly in a coherent feedforward transcriptional network for vascular endothelial development, and a low level of Etv2 expression is sufficient to induce and sustain the endothelial GRN. In contrast, Etv2 induces the erythropoietic GRN indirectly via activation of Tal1, which requires a significantly higher threshold of Etv2 to initiate and sustain erythropoietic development. These results provide important mechanistic insight into the divergence of the endothelial and erythropoietic lineages. Sinha et al. demonstrate that the master regulatory transcription factor Etv2 directly regulates the mouse embryonic endothelial gene-regulatory network (GRN). In contrast, Etv2 regulates the erythropoietic GRN indirectly via the bHLH transcription factor Tal1, making erythropoiesis more sensitive than vasculogenesis to reduced Etv2 gene dosage.
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影响因子：
11.8
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
通讯作者：
Bonifer C
DOI：
10.3791/54150
发表时间：
2016-06-17
期刊：
Journal of visualized experiments : JoVE
影响因子：
--
作者：
Fang JS;Gritz EC;Marcelo KL;Hirschi KK
通讯作者：
Hirschi KK
影响因子：
64.5
作者：
Ginsberg M;James D;Ding BS;Nolan D;Geng F;Butler JM;Schachterle W;Pulijaal VR;Mathew S;Chasen ST;Xiang J;Rosenwaks Z;Shido K;Elemento O;Rabbany SY;Rafii S
通讯作者：
Rafii S
DOI：
10.1038/s41576-020-00311-x
发表时间：
2021-05
期刊：
Nature reviews. Genetics
影响因子：
--
作者：
Kvon EZ;Waymack R;Gad M;Wunderlich Z
通讯作者：
Wunderlich Z
影响因子：
5.3
作者：
Anderson, JP;Dodou, E;Black, BL
通讯作者：
Black, BL