Mitochondrial dysfunction by glyoxalase 1 deficiency disrupts definitive endoderm and alveolar development of human pluripotent stem cells.

ABSTRACT: Normal mitochondrial function is essential for human induced pluripotent stem (hiPS) cell differentiation into definitive endoderm (DE). However, the underlying mechanisms that maintain mitochondrial homeostasis during DE differentiation are not fully elucidated. Here we report that glyoxalase 1 (GLO1) is a novel regulator of DE differentiation and subsequent alveolar development in hiPS cells via maintaining mitochondrial homeostasis. To determine the role of GLO1 in these processes, we first established GLO1-knockout hiPS cells using CRISPR-Cas9-mediated genome deletion and demonstrated that GLO1 deficiency significantly reduced the differentiation efficiency of DE, leading to defects in alveolar epithelial cell differentiation and alveolar organoid development. Moreover, GLO1 deficiency

SUBMITTER: Jeong S 

PROVIDER: S-EPMC12508193 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature