Hepatocyte nuclear factor 1α promotes the differentiation of human embryonic stem cells into insulin producing cells
10.3969/j.issn.1006-6187.2025.08.011
- VernacularTitle:肝细胞核因子1α促进人胚胎干细胞定向分化胰岛素分泌细胞的研究
- Author:
Fei YU
1
;
Rui WEI
;
Tianpei HONG
;
Liyong ZHONG
Author Information
1. 100070 首都医科大学附属北京天坛医院内分泌科
- Publication Type:Journal Article
- Keywords:
Hepatocyte nuclear factor 1α;
Human embryonic stem cells;
Pancreatic islet;
Differentiation
- From:
Chinese Journal of Diabetes
2025;33(8):617-622
- CountryChina
- Language:Chinese
-
Abstract:
Objective To elucidate the regulatory mechanism of hepatocyte nuclear factor 1α(HNF1A)in inducing human embryonic stem cells(hESCs)towards insulin producing cells(IPCs)differentiation.Methods An optimized stepwise protocol was implemented to generate definitive endoderm-derived IPCs.Dynamic HNF1A expression patterns were systematically monitered by qRT-PCR and Western blot.In the third stage(S3)of differentiation,cells were subjected to lentiviral-mediated interventions:respectively HNF1A knockdown(si-HNF1A)with scramble control(si-NC),and HNF1A over expression(oe-HNF1A)with empty vector control(oe-NC).Quantitative analysis of pancreatic lineage markers was performed by qRT-PCR.Glucose stimulated insulin secretion(GSIS)was assessed using ELISA under low glucose(LG)and high glucose(HG)conditions.Results Both HNF1A mRNA and protein levels demonstrated stage-dependent elevation,reaching peak expression at S3 relative to S1(P<0.05).Genetic silencing of HNF1A significantly suppressed key β-cell markers such as Pancreatoduodenal homeobox protein 1,GluT2,Ins compared to controls(P<0.05).Conversely,HNF1A overexpression enhanced transcriptional activation of these markers.Ins secretion increased stimulated by HG than LG in si-NC group.Functional analysis revealed impaired GSIS in si-HNF1A compared with si-NC group(P<0.05),whereas oe-HNF1A cells exhibited augmented GSIS capacity.Conclusions HNF1A positively regulates the IPC differentiation in hESCs,which may play a vital role in potentiating glucose-responsive insulin secretion.
