Peroxisome-dependent and -independent functions of PEX19 in mouse embryonic stem cells.

IF 4.5 2区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES

iScience Pub Date : 2026-09-30 eCollection Date: 2026-10-16 DOI:10.1016/j.isci.2026.117658

Wei Fan, Yi Fang, Joshua Hartsell, Xiaoyue Wu, Xiaojiang Xu, Jian-Liang Li, Xiaojing Liu, Xiaoling Li

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引用次数: 0

Abstract

Pluripotent embryonic stem cells (ESCs) possess a unique cell cycle pattern to support self-renewal and maintain pluripotency, and remodeling of this cycle by developmental cues is a key priming step for lineage commitment. Here we report an unexpected role of PEX19, a chaperone and receptor for peroxisomal membrane proteins, in regulating cell cycle and cell fates of mouse ESCs (mESCs) through a peroxisome-independent mechanism. We show that deletion of Pex19 in mESCs disrupts peroxisome assembly, elevating reactive oxygen species and impairing peroxisomal lipid metabolism. These peroxisomal defects increase cell death and diminish pluripotency. Intriguingly, PEX19 also interacts with α-tubulin to facilitate assembly of mitotic spindles in mitotic mESCs. Consequently, loss of Pex19 disrupts cell cycle progression and hinders the exit from pluripotency upon induction of neural differentiation, ultimately preventing differentiation of neural stem cells. Our study reveals a non-canonical function of PEX19 and underscores the importance of cell cycle regulation in cell fate decisions.

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小鼠胚胎干细胞中PEX19的过氧化物酶体依赖性和非依赖性功能。

多能胚胎干细胞（ESCs）具有独特的细胞周期模式来支持自我更新和维持多能性，而通过发育线索重塑这一周期是谱系承诺的关键启动步骤。在这里，我们报道了PEX19（一种过氧化物酶体膜蛋白的伴侣和受体）通过不依赖过氧化物酶体的机制调节小鼠ESCs （mESCs）的细胞周期和细胞命运的意想不到的作用。我们发现mESCs中Pex19的缺失会破坏过氧化物酶体的组装，增加活性氧并损害过氧化物酶体的脂质代谢。这些过氧化物酶体缺陷增加细胞死亡并降低多能性。有趣的是，PEX19还与α-微管蛋白相互作用，促进有丝分裂mESCs中有丝分裂纺锤体的组装。因此，Pex19的缺失破坏了细胞周期进程，阻碍了神经分化诱导多能性的退出，最终阻止了神经干细胞的分化。我们的研究揭示了PEX19的非规范功能，并强调了细胞周期调节在细胞命运决定中的重要性。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

iScience Multidisciplinary-Multidisciplinary

CiteScore

7.20

自引率

1.70%

发文量

1972

审稿时长

6 weeks

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