Notch signalling influences cell fate decisions and HOX gene induction in axial progenitors

Notch signalling influences cell fate decisions and HOX gene induction in axial progenitors
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Notch信号传导影响轴向祖细胞的细胞命运决定和HOX基因诱导

DOI:
10.1101/2023.06.16.545269
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发表时间:
2023
期刊:
--
影响因子:
--
通讯作者:
Cooper F
Cooper F
中科院分区:
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作者:
Cooper F

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颅后胚胎体的产生依赖于来自神经中胚层祖细胞(NMPs)的脊髓神经外胚层和前体中胚层细胞的协调产生。这个过程是精心策划的前神经和前中胚层转录因子,共表达在NMP与Hox基因,这是必不可少的轴向分配的NMP衍生物。NMP位于后部生长区,其以Wnt、FGF和Notch信号传导组分的表达为标志。虽然Wnt和FGF在影响NMPs诱导和分化中的重要性已得到充分证实,但Notch的确切作用仍不清楚。在这里,我们表明,Wnt/FGF驱动的诱导NMPs从人胚胎干细胞(hESC)依赖于Notch信号。使用人胚胎干细胞衍生的核基质蛋白和鸡胚移植,我们证明,Notch指导前中胚层字符的神经命运的代价。我们表明,Notch也有助于激活HOX基因表达的人NMPs,部分在非细胞自主的方式。最后,我们提供的证据表明,Notch发挥其作用,通过建立一个负反馈回路与FGF信号。
The generation of the post-cranial embryonic body relies on the coordinated production of spinal cord neurectoderm and presomitic mesoderm cells from neuromesodermal progenitors (NMPs). This process is orchestrated by pro-neural and pro-mesodermal transcription factors that are co-expressed in NMPs together with Hox genes, which are essential for axial allocation of NMP derivatives. NMPs reside in a posterior growth region, which is marked by the expression of Wnt, FGF and Notch signalling components. Although the importance of Wnt and FGF in influencing the induction and differentiation of NMPs is well established, the precise role of Notch remains unclear. Here, we show that the Wnt/FGF-driven induction of NMPs from human embryonic stem cells (hESCs) relies on Notch signalling. Using hESC-derived NMPs and chick embryo grafting, we demonstrate that Notch directs a pro-mesodermal character at the expense of neural fate. We show that Notch also contributes to activation of HOX gene expression in human NMPs, partly in a non-cell-autonomous manner. Finally, we provide evidence that Notch exerts its effects via the establishment of a negative-feedback loop with FGF signalling.
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定义人神经中胚层祖细胞衍生物中后腹侧脊髓身份的信号决定因素
DOI: --
发表时间: 2020
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