Wnt signaling promotes hindgut fate commitment through regulating multi-lineage genes during hESC differentiation.
Wnt signaling promotes hindgut fate commitment through regulating multi-lineage genes during hESC differentiation.
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Wnt信号通过调节hESC分化过程中的多谱系基因促进后肠命运承诺
DOI：
10.1016/j.cellsig.2016.09.009
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发表时间：
2017-01
影响因子：
4.8
通讯作者：
Lin X
中科院分区：
文献类型：
--
作者：
Zhang X;Chen Y;Ye Y;Wang J;Wang H;Yuan G;Lin Z;Wu Y;Zhang Y;Lin X
Wnt信号通路在胚胎形态形成和胚后组织的稳态中起重要作用。高水平的Wnt活性抑制前肠身份，并通过形成Wnt信号传导活性梯度沿着前后轴促进后肠命运。在此，我们通过将人胚胎干细胞（hESC）分化为后肠祖细胞来研究Wnt信号在后肠发育中的机制。我们观察到严重的形态学变化时，Wnt信号被阻断Wnt拮抗剂Dkk 1。我们进行了深度转录组测序（RNA-seq），分别鉴定了240个Wnt激活基因和2023个Wnt抑制基因。Wnt靶点簇显示出特定生物学功能的富集，例如Wnt激活靶点中的“胃肠道或骨骼发育”和Wnt抑制靶点中的“神经或免疫系统发育”。此外，我们采用高通量染色质免疫沉淀和深度测序（ChIP-seq）方法来确定Wnt激活的转录因子TCF 7 L2调节转录的基因组区域。我们鉴定了83个Wnt直接靶点候选者，包括后肠标记CDX 2和与形态发生相关的基因（MSX 1，MSX 2，LEF 1，T，PDGFRB等）。通过RNA-seq和ChIP-seq数据的组合分析。总之，我们的研究确定了一系列后肠分化中的直接和间接Wnt靶点，并揭示了Wnt信号转导在调节多谱系分化中的多种机制。
Wnt signaling plays essential roles in both embryonic pattern formation and postembryonic tissue homoestasis. High levels of Wnt activity repress foregut identity and facilitate hindgut fate through forming a gradient of Wnt signaling activity along the anterior-posterior axis. Here, we examined the mechanisms of Wnt signaling in hindgut development by differentiating human embryonic stem cells (hESCs) into the hindgut progenitors. We observed severe morphological changes when Wnt signaling was blocked by using Wnt antagonist Dkk1. We performed deep-transcriptome sequencing (RNA-seq) and identified 240 Wnt-activated genes and 2023 Wnt-repressed genes, respectively. Clusters of Wnt targets showed enrichment in specific biological functions, such as “gastrointestinal or skeletal development” in the Wnt-activated targets and “neural or immune system development” in the Wnt-repressed targets. Moreover, we adopted a high-throughput chromatin immunoprecipitation and deep sequencing (ChIP-seq) approach to identify the genomic regions through which Wnt-activated transcription factor TCF7L2 regulated transcription. We identified 83 Wnt direct target candidates, including the hindgut marker CDX2 and the genes relevant to morphogenesis (MSX1, MSX2, LEF1, T, PDGFRB etc.) through combinatorial analysis of the RNA-seq and ChIP-seq data. Together, our study identified a series of direct and indirect Wnt targets in hindgut differentiation, and uncovered the diverse mechanisms of Wnt signaling in regulating multi-lineage differentiation.
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影响因子：
64.8
作者：
Glinka, A;Wu, W;Niehrs, C
通讯作者：
Niehrs, C
DOI：
10.1242/dev.085654
发表时间：
2013-03
期刊：
Development (Cambridge, England)
影响因子：
--
作者：
Faunes F;Hayward P;Descalzo SM;Chatterjee SS;Balayo T;Trott J;Christoforou A;Ferrer-Vaquer A;Hadjantonakis AK;Dasgupta R;Arias AM
通讯作者：
Arias AM
影响因子：
64.5
作者：
Hallikas, O;Palin, K;Taipale, J
通讯作者：
Taipale, J
影响因子：
23.9
作者：
Ho, Lena;Tan, Shawn Y. X.;Reversade, Bruno
通讯作者：
Reversade, Bruno
影响因子：
11.8
作者：
Kimura-Yoshida, C;Nakano, H;Matsuo, I
通讯作者：
Matsuo, I