人诱导多能干细胞内胚层分化过程中的MIXL1激活

MIXL1 activation in endoderm differentiation of human induced pluripotent stem cells.

作者信息

Osteil Pierre, Withey Sarah, Santucci Nicole, Aryamanesh Nader, Pang Ignatius, Salehin Nazmus, Sun Jane, Qin Annie, Su Jiayi, Knowles Hilary, Li Xiucheng Bella, Cai Simon, Wolvetang Ernst, Tam Patrick P L

机构信息

Embryology Research Unit, Children's Medical Research Institute, University of Sydney, Sydney, Australia.

Australian Institute for Bioengineering and Nanotechnology, University of Queensland, Brisbane, Australia.

出版信息

Stem Cell Reports. 2025 May 13;20(5):102482. doi: 10.1016/j.stemcr.2025.102482. Epub 2025 Apr 24.

DOI:10.1016/j.stemcr.2025.102482

PMID:40280138

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12143138/

Abstract

Human induced pluripotent stem cells (hiPSCs) possess the ability to differentiate into a multitude of cell and tissue types but display heterogeneous propensity of differentiation into specific lineage. Characterization of the transcriptome of 11 hiPSC lines showed that activation of MIXL1 at the early stage of stem cell differentiation correlated with higher efficacy in generating definitive endoderm and advancing differentiation and maturation of endoderm derivatives. Enforced expression of MIXL1 in the endoderm-inefficient hiPSCs enhanced the propensity of endoderm differentiation, suggesting that modulation of key drivers of lineage differentiation can re-wire hiPSC to the desired lineage propensity to generate the requisite stem cell products.

摘要

人诱导多能干细胞（hiPSC）具有分化为多种细胞和组织类型的能力，但在分化为特定谱系时表现出异质性倾向。对11个人诱导多能干细胞系的转录组进行表征显示，在干细胞分化早期MIXL1的激活与生成确定内胚层以及促进内胚层衍生物的分化和成熟的更高效率相关。在内胚层分化效率低下的人诱导多能干细胞中强制表达MIXL1可增强内胚层分化的倾向，这表明对谱系分化关键驱动因子的调控可将人诱导多能干细胞重新导向所需的谱系倾向，以产生所需的干细胞产物。