Bipotential mouse embryonic liver (BMEL) cells spontaneously express Pdx1 and Ngn3 but do not undergo further pancreatic differentiation upon Hes1 down-regulation.
Bipotential mouse embryonic liver (BMEL) cells spontaneously express Pdx1 and Ngn3 but do not undergo further pancreatic differentiation upon Hes1 down-regulation.
复制标题
双能小鼠胚胎肝（BMEL）细胞自发表达PDX1和NGN3，但在HES1下调时不会进一步进行胰腺分化。
DOI：
10.1186/1756-0500-1-136
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发表时间：
2008-12-24
影响因子：
1.8
通讯作者：
Louzier V
中科院分区：
文献类型：
--
作者：
Delisle JC;Martignat L;Bach JM;Bösch S;Louzier V
肝胰腺转化为β细胞工程治疗1型糖尿病提供了新的可能性。在肝细胞的可能来源中，我们专注于BMEL细胞。这些未转化的小鼠胚胎肝细胞已从不同的近交系小鼠品系中可重复地分离出来，并具有在体外和体内分化为肝细胞和胆管细胞的潜力。引人注目的是，我们发现贴壁BMEL细胞显示与多能胰腺前体细胞的功能相似性，即Pdx 1和Ngn 3表达，并在漂浮聚集体培养中进一步表达Hnf6。Hes1是Ngn 3和胰腺内分泌定型的直接阻遏物，在贴壁BMEL细胞中表达，并在聚集培养中随时间推移而降低。然而，Hes1的减少未能启动晚期胰腺内分泌转录因子的激活。在这里，我们报告说，BMEL细胞的胰腺内分泌祖细胞的功能。在糖尿病研究领域中，BMEL细胞对于研究在肝脏向胰腺转化中对体外β细胞成熟至关重要的诱导信号具有潜在的意义。
Liver-to-pancreas conversion offers new possibilities for β-cell engineering for type 1 diabetes therapy. Among conceivable sources of liver cells, we focused on BMEL cells. These untransformed mouse embryonic liver cells have been reproducibly isolated from different inbred mice strains and have the potential to differentiate into hepatocytes and cholangiocytes in vitro and in vivo. Strikingly, we find here that adherent BMEL cells display functional similarities with multipotent pancreatic precursor cells, namely Pdx1 and Ngn3 expression, and further express Hnf6 in floating aggregate culture. Hes1, a direct repressor of Ngn3 and pancreatic endocrine commitment, is expressed in adherent BMEL cells and decreases with time in aggregate culture. However, Hes1 decrease fails to initiate activation of late-stage pancreatic endocrine transcription factors. Here we report that BMEL cells present features of pancreatic endocrine progenitor cells. In the field of diabetes research, BMEL cells are of potential interest for the study of inductive signals critical for in vitro β-cell maturation in-liver-to-pancreas conversion.