Genomic Programming of Beta Cells Laboratory, Institut d'Investigacions Biomèdiques August Pi i Sunyer, 08036 Barcelona, Spain.
Dev Cell. 2009 Dec;17(6):849-60. doi: 10.1016/j.devcel.2009.11.003.
A longstanding unsettled question is whether pancreatic beta cells originate from exocrine duct cells. We have now used genetic labeling to fate map embryonic and adult pancreatic duct cells. We show that Hnf1beta+ cells of the trunk compartment of the early branching pancreas are precursors of acinar, duct, and endocrine lineages. Hnf1beta+ cells subsequent form the embryonic duct epithelium, which gives rise to both ductal and endocrine lineages, but not to acinar cells. By the end of gestation, the fate of Hnf1beta+ duct cells is further restrained. We provide compelling evidence that the ductal epithelium does not make a significant contribution to acinar or endocrine cells during neonatal growth, during a 6 month observation period, or during beta cell growth triggered by ligation of the pancreatic duct or by cell-specific ablation with alloxan followed by EGF/gastrin treatment. Thus, once the ductal epithelium differentiates it has a restricted plasticity, even under regenerative settings.
一个长期存在的悬而未决的问题是胰腺β细胞是否起源于外分泌导管细胞。我们现在已经使用遗传标记来追踪胚胎和成年胰腺导管细胞的命运。我们表明，早期分支胰腺干部分支的 Hnf1β+细胞是腺泡、导管和内分泌谱系的前体细胞。Hnf1β+细胞随后形成胚胎导管上皮，其产生导管和内分泌谱系，但不产生腺泡细胞。在妊娠末期，Hnf1β+导管细胞的命运进一步受到限制。我们提供了令人信服的证据表明，在新生儿生长期间、6 个月的观察期间、结扎胰腺导管或用链脲佐菌素进行细胞特异性消融后用表皮生长因子/胃泌素处理引发β细胞生长期间，导管上皮对腺泡或内分泌细胞没有显著贡献。因此，即使在再生环境下，一旦导管上皮分化，其可塑性也受到限制。
