Early anteroposterior regionalisation of human neural crest is shaped by a pro-mesodermal factor.
Early anteroposterior regionalisation of human neural crest is shaped by a pro-mesodermal factor.
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DOI：
10.7554/elife.74263
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发表时间：
2022-09-26
期刊：
影响因子：
7.7
通讯作者：
Tsakiridis A
中科院分区：
文献类型：
--
作者：
Gogolou A;Souilhol C;Granata I;Wymeersch FJ;Manipur I;Wind M;Frith TJR;Guarini M;Bertero A;Bock C;Halbritter F;Takasato M;Guarracino MR;Tsakiridis A
神经脊(NC)是一种重要的多能胚胎细胞群，其受损的特性导致各种发育缺陷，通常是以前后轴水平特异性的方式。人类NC细胞正确的A-P区域化背后的机制仍然难以捉摸。最近的研究表明，躯干NC细胞被认为是儿童肿瘤神经母细胞瘤的前体细胞，来自于具有神经中胚层潜能的颅后体祖细胞。在这里，我们使用人类胚胎干细胞分化来定义神经中胚层祖细胞(NMP)来源的NC细胞是如何获得后轴身份的。我们发现，前中胚层转录因子TBXT与WNT信号效应器一起介导了NC/脊髓后部的早期区域化。这是由TBXT驱动的染色质重塑，通过与HOX基因簇和其他后部调节相关基因座内的关键增强子结合来实现的。这一最初的后部化事件之后是第二阶段的躯干HOX基因控制，标志着NMP向其TBXT阴性的NC/脊髓衍生品分化，并主要依赖于成纤维细胞生长因子信号。我们的工作揭示了TBXT在影响后路NC命运中以前未知的作用，并指出存在时间上离散的、依赖于细胞类型的后路轴向同一性控制模式。
The neural crest (NC) is an important multipotent embryonic cell population and its impaired specification leads to various developmental defects, often in an anteroposterior (A-P) axial level-specific manner. The mechanisms underlying the correct A-P regionalisation of human NC cells remain elusive. Recent studies have indicated that trunk NC cells, the presumed precursors of childhood tumour neuroblastoma, are derived from neuromesodermal-potent progenitors of the postcranial body. Here we employ human embryonic stem cell differentiation to define how neuromesodermal progenitor (NMP)-derived NC cells acquire a posterior axial identity. We show that TBXT, a pro-mesodermal transcription factor, mediates early posterior NC/spinal cord regionalisation together with WNT signalling effectors. This occurs by TBXT-driven chromatin remodelling via its binding in key enhancers within HOX gene clusters and other posterior regulator-associated loci. This initial posteriorisation event is succeeded by a second phase of trunk HOX gene control that marks the differentiation of NMPs toward their TBXT-negative NC/spinal cord derivatives and relies predominantly on FGF signalling. Our work reveals a previously unknown role of TBXT in influencing posterior NC fate and points to the existence of temporally discrete, cell type-dependent modes of posterior axial identity control.
在爱尔兰大型研究人群中评估 64 个候选单核苷酸多态性作为神经管缺陷的危险因素。
影响因子：
2
作者：
Carter, Tonia C.;Pangilinan, Faith;Troendle, James F.;Molloy, Anne M.;VanderMeer, Julia;Mitchell, Adam;Kirke, Peadar N.;Conley, Mary R.;Shane, Barry;Scott, John M.;Brody, Lawrence C.;Mills, James L.
通讯作者：
Mills, James L.