Gu Guoqiang, Dubauskaite Jolanta, Melton Douglas A
Department of Molecular and Cellular Biology, and Howard Hughes Medical Institute, Harvard University, Cambridge, MA 02138, USA.
Development. 2002 May;129(10):2447-57. doi: 10.1242/dev.129.10.2447.
The location and lineage of cells that give rise to endocrine islets during embryogenesis has not been established nor has the origin or identity of adult islet stem cells. We have employed an inducible Cre-ER(TM)-LoxP system to indelibly mark the progeny of cells expressing either Ngn3 or Pdx1 at different stages of development. The results provide direct evidence that NGN3+ cells are islet progenitors during embryogenesis and in adult mice. In addition, we find that cells expressing Pdx1 give rise to all three types of pancreatic tissue: exocrine, endocrine and duct. Furthermore, exocrine and endocrine cells are derived from Pdx1-expressing progenitors throughout embryogenesis. By contrast, the pancreatic duct arises from PDX1+ progenitors that are set aside around embryonic day 10.5 (E9.5-E11.5). These findings suggest that lineages for exocrine, endocrine islet and duct progenitors are committed at mid-gestation.
胚胎发育过程中产生内分泌胰岛的细胞的位置和谱系尚未明确，成体胰岛干细胞的起源或特性也不清楚。我们采用了一种可诱导的Cre-ER(TM)-LoxP系统，对在不同发育阶段表达Ngn3或Pdx1的细胞的后代进行永久性标记。结果提供了直接证据，表明NGN3+细胞在胚胎发育期间及成年小鼠中是胰岛祖细胞。此外，我们发现表达Pdx1的细胞可产生胰腺的所有三种组织类型：外分泌组织、内分泌组织和导管。而且，在整个胚胎发育过程中，外分泌细胞和内分泌细胞均源自表达Pdx1的祖细胞。相比之下，胰腺导管源自大约在胚胎第10.5天（E9.5 - E11.5）分离出来的PDX1+祖细胞。这些发现表明，外分泌、内分泌胰岛和导管祖细胞的谱系在妊娠中期就已确定。
