Preliminary Exposure to Histone Deacetylase Inhibitors Changes the Direction of Human iPSCs’ Differentiation with the Formation of Cardiospheres Instead of Skin Organoids

Pub Date : 2023-12-01 DOI:10.1134/s1062360423060024
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Abstract

Pluripotent stem cells (PSCs) are a unique cell type that can differentiate into all cell types in the body. In PSC culture, subpopulations with different levels of pluripotency may exist, which leads to different results during their differentiation. One of the key factors that determine the state of pluripotency and influence the differentiation potential of PSCs is the epigenetic state of cells, including the level of histone deacetylation. Activation of histone deacetylase (HDAC) in human and mouse PSCs increases the percentage of heterochromatin. In this work, we used a protocol for the differentiation of embryoid bodies from induced human pluripotent hiPSC cells designed for the formation of ectoderm and neuroectoderm with their subsequent development into skin organoids. However, after hiPSCs were exposed to HDAC inhibitors (sodium butyrate and valproic acid), the direction of their differentiation changed: mesoderm was formed, which subsequently developed into contracting cardiospheres.

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组蛋白去乙酰化酶抑制剂的初步暴露改变了人类 iPSCs 的分化方向,形成了心球而非皮肤器官组织
摘要 多能干细胞(PSCs)是一种独特的细胞类型,可分化成体内所有类型的细胞。在多能干细胞的培养过程中,可能存在不同多能性水平的亚群,这导致它们在分化过程中产生不同的结果。决定多能性状态并影响造血干细胞分化潜能的关键因素之一是细胞的表观遗传状态,包括组蛋白去乙酰化水平。在人和小鼠的造血干细胞中激活组蛋白去乙酰化酶(HDAC)会增加异染色质的比例。在这项工作中,我们使用了一种从诱导的人类多能 hiPSC 细胞分化出胚状体的方案,该方案旨在形成外胚层和神经外胚层,随后将其发育成皮肤器官组织。然而,当 hiPSC 暴露于 HDAC 抑制剂(丁酸钠和丙戊酸)后,它们的分化方向发生了变化:形成了中胚层,随后发育成收缩的心球。
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