3D球体通过p300介导的H3K56乙酰化促进人脂肪来源的间充质干细胞分化为肝细胞样细胞。

IF 5.4 2区 医学 Q1 CELL & TISSUE ENGINEERING
Yanrong Yu, Haina Huang, Junsong Ye, Yumei Li, Renjian Xie, Liping Zeng, Yushan Huang, Tai Zeng, Dan Luo, Jianing Zhong, Weijie Peng
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引用次数: 0

摘要

从间充质干细胞(MSC)分化而来的肝细胞样细胞(HLCs)为药物筛选和基于细胞的再生治疗提供了宝贵的资源。将HLCs分化为3D球体可增强其表型和功能。然而,MSCs肝源性分化的分子机制尚不完全清楚。在这项研究中,我们在2D和3D培养中从人脂肪来源的间充质干细胞(hADMSC)中产生了HLCs。我们对来源于2D和3D分化的HLCs进行了乙酰蛋白质组学测定,并鉴定了两种分化细胞之间H3K56乙酰化的差异变化。我们的研究结果表明,3D分化通过提高H3K56的乙酰化水平来激活ALB基因转录,从而增强HLCs的表型和功能,并进一步促进其成熟。值得注意的是,在肝细胞分化过程中,抑制p300降低了H3K56的乙酰化水平,导致HLCs的表型和功能降低,而p300的激活促进了肝细胞分化,表明p300在这一过程中起着关键作用。总之,我们的研究证明了3D球体分化通过促进p300介导的H3K56乙酰化促进hADMSC分化为HLCs的潜在机制,这可能在肝脏再生和疾病建模中具有重要的临床应用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
3D Spheroids Facilitate Differentiation of Human Adipose-Derived Mesenchymal Stem Cells into Hepatocyte-Like Cells via p300-Mediated H3K56 Acetylation.

Hepatocyte-like cells (HLCs) that are differentiated from mesenchymal stem cells (MSCs) provide a valuable resource for drug screening and cell-based regeneration therapy. Differentiating HLCs into 3D spheroids enhances their phenotypes and functions. However, the molecular mechanisms underlying MSCs hepatogenic differentiation are not fully understood. In this study, we generated HLCs from human adipose-derived mesenchymal stem cells (hADMSCs) in both 2D and 3D cultures. We performed an acetyl-proteomics assay on the HLCs derived from both 2D and 3D differentiation and identified a differential change in H3K56 acetylation between the 2 differentiated cells. Our findings revealed that 3D differentiation activated ALB gene transcription by increasing the acetylation level of H3K56, thereby enhancing the phenotypes and functions of HLCs and further promoting their maturation. Notably, inhibiting p300 reduced the acetylation level of H3K56 during hepatogenic differentiation, leading to decreased phenotypes and functions of HLCs, whereas activation of p300 promoted hepatogenic differentiation, suggesting that p300 plays a critical role in this process. In summary, our study demonstrates a potential mechanism through which 3D spheroids differentiation facilitates hADMSCs differentiation into HLCs by promoting p300-mediated H3K56 acetylation, which could have significant clinical applications in liver regeneration and disease modeling.

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来源期刊
Stem Cells Translational Medicine
Stem Cells Translational Medicine CELL & TISSUE ENGINEERING-
CiteScore
12.90
自引率
3.30%
发文量
140
审稿时长
6-12 weeks
期刊介绍: STEM CELLS Translational Medicine is a monthly, peer-reviewed, largely online, open access journal. STEM CELLS Translational Medicine works to advance the utilization of cells for clinical therapy. By bridging stem cell molecular and biological research and helping speed translations of emerging lab discoveries into clinical trials, STEM CELLS Translational Medicine will help move applications of these critical investigations closer to accepted best patient practices and ultimately improve outcomes. The journal encourages original research articles and concise reviews describing laboratory investigations of stem cells, including their characterization and manipulation, and the translation of their clinical aspects of from the bench to patient care. STEM CELLS Translational Medicine covers all aspects of translational cell studies, including bench research, first-in-human case studies, and relevant clinical trials.
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