2. Academic Validation
  3. 3D Spheroids Facilitate Differentiation of Human Adipose-Derived Mesenchymal Stem Cells into Hepatocyte-Like Cells via p300-Mediated H3K56 Acetylation

3D Spheroids Facilitate Differentiation of Human Adipose-Derived Mesenchymal Stem Cells into Hepatocyte-Like Cells via p300-Mediated H3K56 Acetylation

  • Stem Cells Transl Med. 2024 Feb 14;13(2):151-165. doi: 10.1093/stcltm/szad076.
Yanrong Yu 1 2,  Haina Huang 1 3,  Junsong Ye 1 3 4,  Yumei Li 1 5,  Renjian Xie 1 6,  Liping Zeng 1,  Yushan Huang 7,  Tai Zeng 1,  Dan Luo 8,  Jianing Zhong 1 3,  Weijie Peng 1 3
Affiliations

Affiliations

  • 1 Key Laboratory of Biomaterials and Biofabrication for Tissue Engineering in Jiangxi Province, Gannan Medical University, Ganzhou, People's Republic of China.
  • 2 Center for Molecular Diagnosis and Precision Medicine, and Department of Clinical Laboratory, The First Affiliated Hospital of Nanchang University, Nanchang, People's Republic of China.
  • 3 Key Laboratory of Prevention and Treatment of Cardiovascular and Cerebrovascular Diseases, Ministry of Education, Gannan Medical University, Ganzhou, People's Republic of China.
  • 4 Subcenter for Stem Cell Clinical Translation, The First Affiliated Hospital of Gannan Medical University, Ganzhou, People's Republic of China.
  • 5 School of Basic Medicine, Gannan Medical University, Ganzhou, People's Republic of China.
  • 6 School of Medical Information Engineering, Gannan Medical University, Ganzhou, People's Republic of China.
  • 7 Center for Evidence Based Medical and Clinical Research, The First Affiliated Hospital of Gannan Medical University, Ganzhou, People's Republic of China.
  • 8 Department of Physiology, School of Basic Medicine, Nanchang University, Nanchang, People's Republic of China.
PMID: 37936499 DOI: 10.1093/stcltm/szad076
Abstract

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.

Keywords

3D spheroids; H3K56 acetylation; hepatogenic differentiation; human adipose-derived mesenchymal stem cells; p300.

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