Ex vivo analysis of acinar and endocrine cell development in the human embryonic pancreas
Ex vivo analysis of acinar and endocrine cell development in the human embryonic pancreas
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DOI：
10.1002/dvdy.20547
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发表时间：
2005-10-01
影响因子：
2.5
通讯作者：
Scharfmann, R
中科院分区：
文献类型：
--
作者：
Castaing, M;Duvillié, B;Scharfmann, R
与关于啮齿动物胰腺发育的大量数据相比，关于人类胰腺发育的信息很少。我们之前描述了一种从人胚胎胰腺发育成熟的β细胞的模型：将人胚胎胰腺移植到SCID小鼠的肾被膜下，然后在移植物中观察到β细胞的发育。在这里，我们发现在这个模型中，不仅有β细胞，还有其他内分泌细胞、腺泡细胞和导管。然后，我们使用这个模型来探索人类胚胎胰腺中腺泡细胞和β细胞发育的机制。BrdU脉冲/Chase实验证实了腺泡细胞的克隆性发育：第一批出现的腺泡细胞增殖，从而扩大了腺泡细胞的数量。相反，胰岛前体细胞的增殖以及随后的胰岛细胞分化对胰岛细胞的发育起着调控作用。然后我们发现，表达PDX1的早期祖细胞增殖，而表达Ngn3的晚期内分泌祖细胞不增殖。人类胚胎胰腺早期内分泌祖细胞的这种增殖能力可能为获得人类β细胞的扩增提供了希望。
In contrast to the considerable body of data on pancreas development in rodents, information on pancreas development in humans is scant. We previously described a model in which mature beta cells developed from human embryonic pancreas: human embryonic pancreas was grafted under the kidney capsule of scid mice, beta cells were then seen to develop in the graft. Here, we showed that not only beta cells, but also other endocrine cells, acinar cells and ducts develop in this model. We then used this model to probe the mechanisms underlying acinar and beta cell development in the human embryonic pancreas. BrdU pulse/chase experiments produced evidence of clonal acinar cell development: the first acinar cells to appear proliferated, thereby expanding the acinar cell population. In contrast, beta cell development was regulated by the proliferation of pancreatic progenitor cells, followed by beta-cell differentiation. We then showed that early progenitors expressing PDX1 proliferated, whereas late endocrine progenitors expressing Ngn3 did not. This proliferative capacity of early endocrine progenitor cells in embryonic human pancreas may hold promise for obtaining human beta-cell expansion.