Lineage determinants in early endocrine development.
Lineage determinants in early endocrine development.
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DOI：
10.1016/j.semcdb.2012.06.005
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发表时间：
2012-08
影响因子：
7.3
通讯作者：
Wright, Christopher V. E.
中科院分区：
文献类型：
--
作者：
Rieck, Sebastian;Bankaitis, Eric D.;Wright, Christopher V. E.
关键词：
Pancreas organogenesisMultipotent progenitor cellTranscription factorTubulogenesisTip-trunk compartmentalizationPlexus remodelingBranching morphogenesisEndocrine subtype specification and maturationIsletHuman pancreasReprogrammingHuman embryonic stem cellsTranscription factorGene regulatory networkPrimary transitionSecondary transition
胰腺内分泌细胞是由一个动态的上皮细胞产生的，与任何发育中的器官一样，这一过程是由时空调节的细胞间信号和自主基因调控网络的相互作用程序驱动的。这些算法的工作原理是推动祖细胞和过渡性中间细胞通过一系列类似火车站的切换决策来调节特定分化轨道上的通量。在过去的20年里，对胰腺器官发生的广泛研究，在很大程度上受到了通过移植治疗恢复糖尿病患者功能β细胞群的潜力的推动，正在推进我们对内分泌谱系偏向如何建立和分配的认识。该领域的目标是生成一个详细的蓝图，描述异质细胞群体如何相互作用和响应，以及其他影响，如细胞外基质，以逐渐进入精细和成熟的细胞状态。在这里，我们强调信号编码和转录网络如何在一个复杂的和动态的结构中决定内分泌谱系，主要基于对小鼠的研究。这一过程始于多能祖细胞（MPC）分化为胰腺芽，随后经历一个新提出的涉及上皮丛形成-重塑的时期，并以连接血管和周围神经系统的聚集性内分泌胰岛的形成结束。发展这一知识基础，并增加对小鼠和人类之间直接比较的重视，将产生更完整、更集中的胰腺发育图景，从而为人类胚胎干细胞或诱导多能干细胞（hESC, iPSC）的β细胞定向分化提供信息。此外，通过定义允许内胚层或胰腺细胞群可控重编程的条件，更深入的了解可能会提供令人惊讶的治疗角度。
Pancreatic endocrine cells are produced from a dynamic epithelium in a process that, as in any developing organ, is driven by interacting programs of spatiotemporally regulated intercellular signals and autonomous gene regulatory networks. These algorithms work to push progenitors and their transitional intermediates through a series of railroad-station-like switching decisions to regulate flux along specific differentiation tracks. Extensive research on pancreas organogenesis over the last 20 years, greatly spurred by the potential to restore functional β-cell mass in diabetic patients by transplantation therapy, is advancing our knowledge of how endocrine lineage bias is established and allocation is promoted. The field is working towards the goal of generating a detailed blueprint of how heterogeneous cell populations interact and respond to each other, and other influences such as the extracellular matrix, to move into progressively refined and mature cell states. Here, we highlight how signaling codes and transcriptional networks might determine endocrine lineage within a complex and dynamic architecture, based largely on studies in the mouse. The process begins with the designation of multipotent progenitor cells (MPC) to pancreatic buds that subsequently move through a newly proposed period involving epithelial plexus formation-remodeling, and ends with formation of clustered endocrine islets connected to the vascular and peripheral nervous systems. Developing this knowledge base, and increasing the emphasis on direct comparisons between mouse and human, will yield a more complete and focused picture of pancreas development, and thereby inform β-cell-directed differentiation from human embryonic stem or induced pluripotent stem cells (hESC, iPSC). Additionally, a deeper understanding may provide surprising therapeutic angles by defining conditions that allow the controllable reprogramming of endodermal or pancreatic cell populations.
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