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Osteogenic Differentiation Potential of Mesenchymal Stem Cells Using Single Cell Multiomic Analysis

Mesenchymal stem cells (MSC) are multipotent stem cells that can differentiate into multiple cell types, including osteoblasts, chondrocytes, and adipocytes. Osteoblast differentiation is reduced during osteoporosis development, resulting in reduced bone formation. Further, MSC isolated from differe...

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Autores principales: Chen, Duojiao, Liu, Sheng, Chu, Xiaona, Reiter, Jill, Gao, Hongyu, McGuire, Patrick, Yu, Xuhong, Xuei, Xiaoling, Liu, Yichen, Wan, Jun, Fang, Fang, Liu, Yunlong, Wang, Yue
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10606235/
https://www.ncbi.nlm.nih.gov/pubmed/37895219
http://dx.doi.org/10.3390/genes14101871
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author Chen, Duojiao
Liu, Sheng
Chu, Xiaona
Reiter, Jill
Gao, Hongyu
McGuire, Patrick
Yu, Xuhong
Xuei, Xiaoling
Liu, Yichen
Wan, Jun
Fang, Fang
Liu, Yunlong
Wang, Yue
author_facet Chen, Duojiao
Liu, Sheng
Chu, Xiaona
Reiter, Jill
Gao, Hongyu
McGuire, Patrick
Yu, Xuhong
Xuei, Xiaoling
Liu, Yichen
Wan, Jun
Fang, Fang
Liu, Yunlong
Wang, Yue
author_sort Chen, Duojiao
collection PubMed
description Mesenchymal stem cells (MSC) are multipotent stem cells that can differentiate into multiple cell types, including osteoblasts, chondrocytes, and adipocytes. Osteoblast differentiation is reduced during osteoporosis development, resulting in reduced bone formation. Further, MSC isolated from different donors possess distinct osteogenic capacity. In this study, we used single-cell multiomic analysis to profile the transcriptome and epigenome of MSC from four healthy donors. Data were obtained from ~1300 to 1600 cells for each donor. These cells were clustered into four groups, indicating that MSC from different donors have distinct chromatin accessible regulatory elements for regulating gene expression. To investigate the mechanism by which MSC undergo osteogenic differentiation, we used the chromatin accessibility data from the single-cell multiome data to identify individual-specific enhancer–promoter pairs and evaluated the expression levels and activities of the transcriptional regulators. The MSC from four donors showed distinct differentiation potential into osteoblasts. MSC of donor 1 showed the largest average motif activities, indicating that MSC from donor 1 was most likely to differentiate into osteoblasts. The results of our validation experiments were consistent with the bioinformatics prediction. We also tested the enrichment of genome-wide association study (GWAS) signals of several musculoskeletal disease traits in the patient-specific chromatin accessible regions identified in the single-cell multiome data, including osteoporosis, osteopenia, and osteoarthritis. We found that osteoarthritis-associated variants were only enriched in the regions identified from donor 4. In contrast, osteoporosis and osteopenia variants were enriched in regions from donor 1 and least enriched in donor 4. Since osteoporosis and osteopenia are related to the density of bone cells, the enrichment of variants from these traits should be correlated with the osteogenic potential of MSC. In summary, this study provides large-scale data to link regulatory elements with their target genes to study the regulatory relationships during the differentiation of mesenchymal stem cells and provide a deeper insight into the gene regulatory mechanism.
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spelling pubmed-106062352023-10-28 Osteogenic Differentiation Potential of Mesenchymal Stem Cells Using Single Cell Multiomic Analysis Chen, Duojiao Liu, Sheng Chu, Xiaona Reiter, Jill Gao, Hongyu McGuire, Patrick Yu, Xuhong Xuei, Xiaoling Liu, Yichen Wan, Jun Fang, Fang Liu, Yunlong Wang, Yue Genes (Basel) Article Mesenchymal stem cells (MSC) are multipotent stem cells that can differentiate into multiple cell types, including osteoblasts, chondrocytes, and adipocytes. Osteoblast differentiation is reduced during osteoporosis development, resulting in reduced bone formation. Further, MSC isolated from different donors possess distinct osteogenic capacity. In this study, we used single-cell multiomic analysis to profile the transcriptome and epigenome of MSC from four healthy donors. Data were obtained from ~1300 to 1600 cells for each donor. These cells were clustered into four groups, indicating that MSC from different donors have distinct chromatin accessible regulatory elements for regulating gene expression. To investigate the mechanism by which MSC undergo osteogenic differentiation, we used the chromatin accessibility data from the single-cell multiome data to identify individual-specific enhancer–promoter pairs and evaluated the expression levels and activities of the transcriptional regulators. The MSC from four donors showed distinct differentiation potential into osteoblasts. MSC of donor 1 showed the largest average motif activities, indicating that MSC from donor 1 was most likely to differentiate into osteoblasts. The results of our validation experiments were consistent with the bioinformatics prediction. We also tested the enrichment of genome-wide association study (GWAS) signals of several musculoskeletal disease traits in the patient-specific chromatin accessible regions identified in the single-cell multiome data, including osteoporosis, osteopenia, and osteoarthritis. We found that osteoarthritis-associated variants were only enriched in the regions identified from donor 4. In contrast, osteoporosis and osteopenia variants were enriched in regions from donor 1 and least enriched in donor 4. Since osteoporosis and osteopenia are related to the density of bone cells, the enrichment of variants from these traits should be correlated with the osteogenic potential of MSC. In summary, this study provides large-scale data to link regulatory elements with their target genes to study the regulatory relationships during the differentiation of mesenchymal stem cells and provide a deeper insight into the gene regulatory mechanism. MDPI 2023-09-26 /pmc/articles/PMC10606235/ /pubmed/37895219 http://dx.doi.org/10.3390/genes14101871 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Chen, Duojiao
Liu, Sheng
Chu, Xiaona
Reiter, Jill
Gao, Hongyu
McGuire, Patrick
Yu, Xuhong
Xuei, Xiaoling
Liu, Yichen
Wan, Jun
Fang, Fang
Liu, Yunlong
Wang, Yue
Osteogenic Differentiation Potential of Mesenchymal Stem Cells Using Single Cell Multiomic Analysis
title Osteogenic Differentiation Potential of Mesenchymal Stem Cells Using Single Cell Multiomic Analysis
title_full Osteogenic Differentiation Potential of Mesenchymal Stem Cells Using Single Cell Multiomic Analysis
title_fullStr Osteogenic Differentiation Potential of Mesenchymal Stem Cells Using Single Cell Multiomic Analysis
title_full_unstemmed Osteogenic Differentiation Potential of Mesenchymal Stem Cells Using Single Cell Multiomic Analysis
title_short Osteogenic Differentiation Potential of Mesenchymal Stem Cells Using Single Cell Multiomic Analysis
title_sort osteogenic differentiation potential of mesenchymal stem cells using single cell multiomic analysis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10606235/
https://www.ncbi.nlm.nih.gov/pubmed/37895219
http://dx.doi.org/10.3390/genes14101871
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