Endocrine Cell Clustering During Human Pancreas Development
Endocrine Cell Clustering During Human Pancreas Development
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DOI：
10.1369/jhc.2009.953307
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发表时间：
2009-09-01
影响因子：
3.2
通讯作者：
Diez, Juan A.
中科院分区：
文献类型：
--
作者：
Jeon, Jongmin;Correa-Medina, Mayrin;Diez, Juan A.
开发有效的，可重复的协议，在体外定向分化的人胚胎干细胞（hES）细胞成胰岛素产生β细胞将大大受益于增加知识的时空表达谱的关键指导因素参与人内分泌细胞的生成。妊娠7 - 21周的人胎儿胰腺，在妊娠终止后立即同意后收集，并进行免疫染色，原位杂交和实时RT-PCR表达分析。胰岛样结构从大约第12周开始出现，与成人胰岛中观察到的混合结构不同，胎儿胰岛最初主要由聚集的胰岛素或胰高血糖素表达细胞形成。所研究的时期（7-22周）与祖细胞增殖的减少和分化的增加、NGN 3表达的起始和分化的内分泌细胞的出现相一致。本研究提供了一个详细的表征胰岛的形成和表达谱的关键内在和外在因素在人类胰腺发育。该信息有利于开发有效的方案，该方案将允许hES细胞体外分化为胰岛素产生细胞。（J Histochem Cytochem 57：811- 824，2009）
The development of efficient, reproducible protocols for directed in vitro differentiation of human embryonic stem (hES) cells into insulin-producing beta cells will benefit greatly from increased knowledge regarding the spatiotemporal expression profile of key instructive factors involved in human endocrine cell generation. Human fetal pancreases 7 to 21 weeks of gestational age, were collected following consent immediately after pregnancy termination and processed for immunostaining, in situ hybridization, and real-time RT-PCR expression analyses. Islet-like structures appear from approximately week 12 and, unlike the mixed architecture observed in adult islets, fetal islets are initially formed predominantly by aggregated insulin- or glucagon-expressing cells. The period studied (7-22 weeks) coincides with a decrease in the proliferation and an increase in the differentiation of the progenitor cells, the initiation of NGN3 expression, and the appearance of differentiated endocrine cells. The present study provides a detailed characterization of islet formation and expression profiles of key intrinsic and extrinsic factors during human pancreas development. This information is beneficial for the development of efficient protocols that will allow guided in vitro differentiation of hES cells into insulin-producing cells. (J Histochem Cytochem 57:811-824,2009)