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Single-Cell Transcriptome Integration Analysis Reveals the Correlation Between Mesenchymal Stromal Cells and Fibroblasts

Background: Mesenchymal stromal cells (MSCs) and fibroblasts show similar morphology, surface marker expression, and proliferation, differentiation, and immunomodulatory capacities. These similarities not only blur their cell identities but also limit their application. Methods: We performed single-...

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Autores principales: Fan, Chuiqin, Liao, Maochuan, Xie, Lichun, Huang, Liangping, Lv, Siyu, Cai, Siyu, Su, Xing, Wang, Yue, Wang, Hongwu, Wang, Manna, Liu, Yulin, Wang, Yu, Guo, Huijie, Yang, Hanhua, Liu, Yufeng, Wang, Tianyou, Ma, Lian
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8961367/
https://www.ncbi.nlm.nih.gov/pubmed/35360851
http://dx.doi.org/10.3389/fgene.2022.798331
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author Fan, Chuiqin
Liao, Maochuan
Xie, Lichun
Huang, Liangping
Lv, Siyu
Cai, Siyu
Su, Xing
Wang, Yue
Wang, Hongwu
Wang, Manna
Liu, Yulin
Wang, Yu
Guo, Huijie
Yang, Hanhua
Liu, Yufeng
Wang, Tianyou
Ma, Lian
author_facet Fan, Chuiqin
Liao, Maochuan
Xie, Lichun
Huang, Liangping
Lv, Siyu
Cai, Siyu
Su, Xing
Wang, Yue
Wang, Hongwu
Wang, Manna
Liu, Yulin
Wang, Yu
Guo, Huijie
Yang, Hanhua
Liu, Yufeng
Wang, Tianyou
Ma, Lian
author_sort Fan, Chuiqin
collection PubMed
description Background: Mesenchymal stromal cells (MSCs) and fibroblasts show similar morphology, surface marker expression, and proliferation, differentiation, and immunomodulatory capacities. These similarities not only blur their cell identities but also limit their application. Methods: We performed single-cell transcriptome sequencing of the human umbilical cord and foreskin MSCs (HuMSCs and FSMSCs) and extracted the single-cell transcriptome data of the bone marrow and adipose MSCs (BMSCs and ADMSCs) from the Gene Expression Omnibus (GEO) database. Then, we performed quality control, batch effect correction, integration, and clustering analysis of the integrated single-cell transcriptome data from the HuMSCs, FMSCs, BMSCs, and ADMSCs. The cell subsets were annotated based on the surface marker phenotypes for the MSCs (CD105 ( + ), CD90 (+), CD73 (+), CD45 (−), CD34 (−), CD19 (−), HLA-DRA (−), and CD11b (−)), fibroblasts (VIM (+), PECAM1 (−), CD34 (−), CD45 (−), EPCAM (−), and MYH11 (−)), and pericytes (CD146 (+), PDGFRB (+), PECAM1 (−), CD34 (−), and CD45 (−)). The expression levels of common fibroblast markers (ACTA2, FAP, PDGFRA, PDGFRB, S100A4, FN1, COL1A1, POSTN, DCN, COL1A2, FBLN2, COL1A2, DES, and CDH11) were also analyzed in all cell subsets. Finally, the gene expression profiles, differentiation status, and the enrichment status of various gene sets and regulons were compared between the cell subsets. Results: We demonstrated 15 distinct cell subsets in the integrated single-cell transcriptome sequencing data. Surface marker annotation demonstrated the MSC phenotype in 12 of the 15 cell subsets. C10 and C14 subsets demonstrated both the MSC and pericyte phenotypes. All 15 cell subsets demonstrated the fibroblast phenotype. C8, C12, and C13 subsets exclusively demonstrated the fibroblast phenotype. We identified 3,275 differentially expressed genes, 305 enriched gene sets, and 34 enriched regulons between the 15 cell subsets. The cell subsets that exclusively demonstrated the fibroblast phenotype represented less primitive and more differentiated cell types. Conclusion: Cell subsets with the MSC phenotype also demonstrated the fibroblast phenotype, but cell subsets with the fibroblast phenotype did not necessarily demonstrate the MSC phenotype, suggesting that MSCs represented a subclass of fibroblasts. We also demonstrated that the MSCs and fibroblasts represented highly heterogeneous populations with distinct cell subsets, which could be identified based on the differentially enriched gene sets and regulons that specify proliferating, differentiating, metabolic, and/or immunomodulatory functions.
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spelling pubmed-89613672022-03-30 Single-Cell Transcriptome Integration Analysis Reveals the Correlation Between Mesenchymal Stromal Cells and Fibroblasts Fan, Chuiqin Liao, Maochuan Xie, Lichun Huang, Liangping Lv, Siyu Cai, Siyu Su, Xing Wang, Yue Wang, Hongwu Wang, Manna Liu, Yulin Wang, Yu Guo, Huijie Yang, Hanhua Liu, Yufeng Wang, Tianyou Ma, Lian Front Genet Genetics Background: Mesenchymal stromal cells (MSCs) and fibroblasts show similar morphology, surface marker expression, and proliferation, differentiation, and immunomodulatory capacities. These similarities not only blur their cell identities but also limit their application. Methods: We performed single-cell transcriptome sequencing of the human umbilical cord and foreskin MSCs (HuMSCs and FSMSCs) and extracted the single-cell transcriptome data of the bone marrow and adipose MSCs (BMSCs and ADMSCs) from the Gene Expression Omnibus (GEO) database. Then, we performed quality control, batch effect correction, integration, and clustering analysis of the integrated single-cell transcriptome data from the HuMSCs, FMSCs, BMSCs, and ADMSCs. The cell subsets were annotated based on the surface marker phenotypes for the MSCs (CD105 ( + ), CD90 (+), CD73 (+), CD45 (−), CD34 (−), CD19 (−), HLA-DRA (−), and CD11b (−)), fibroblasts (VIM (+), PECAM1 (−), CD34 (−), CD45 (−), EPCAM (−), and MYH11 (−)), and pericytes (CD146 (+), PDGFRB (+), PECAM1 (−), CD34 (−), and CD45 (−)). The expression levels of common fibroblast markers (ACTA2, FAP, PDGFRA, PDGFRB, S100A4, FN1, COL1A1, POSTN, DCN, COL1A2, FBLN2, COL1A2, DES, and CDH11) were also analyzed in all cell subsets. Finally, the gene expression profiles, differentiation status, and the enrichment status of various gene sets and regulons were compared between the cell subsets. Results: We demonstrated 15 distinct cell subsets in the integrated single-cell transcriptome sequencing data. Surface marker annotation demonstrated the MSC phenotype in 12 of the 15 cell subsets. C10 and C14 subsets demonstrated both the MSC and pericyte phenotypes. All 15 cell subsets demonstrated the fibroblast phenotype. C8, C12, and C13 subsets exclusively demonstrated the fibroblast phenotype. We identified 3,275 differentially expressed genes, 305 enriched gene sets, and 34 enriched regulons between the 15 cell subsets. The cell subsets that exclusively demonstrated the fibroblast phenotype represented less primitive and more differentiated cell types. Conclusion: Cell subsets with the MSC phenotype also demonstrated the fibroblast phenotype, but cell subsets with the fibroblast phenotype did not necessarily demonstrate the MSC phenotype, suggesting that MSCs represented a subclass of fibroblasts. We also demonstrated that the MSCs and fibroblasts represented highly heterogeneous populations with distinct cell subsets, which could be identified based on the differentially enriched gene sets and regulons that specify proliferating, differentiating, metabolic, and/or immunomodulatory functions. Frontiers Media S.A. 2022-03-07 /pmc/articles/PMC8961367/ /pubmed/35360851 http://dx.doi.org/10.3389/fgene.2022.798331 Text en Copyright © 2022 Fan, Liao, Xie, Huang, Lv, Cai, Su, Wang, Wang, Wang, Liu, Wang, Guo, Yang, Liu, Wang and Ma. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Genetics
Fan, Chuiqin
Liao, Maochuan
Xie, Lichun
Huang, Liangping
Lv, Siyu
Cai, Siyu
Su, Xing
Wang, Yue
Wang, Hongwu
Wang, Manna
Liu, Yulin
Wang, Yu
Guo, Huijie
Yang, Hanhua
Liu, Yufeng
Wang, Tianyou
Ma, Lian
Single-Cell Transcriptome Integration Analysis Reveals the Correlation Between Mesenchymal Stromal Cells and Fibroblasts
title Single-Cell Transcriptome Integration Analysis Reveals the Correlation Between Mesenchymal Stromal Cells and Fibroblasts
title_full Single-Cell Transcriptome Integration Analysis Reveals the Correlation Between Mesenchymal Stromal Cells and Fibroblasts
title_fullStr Single-Cell Transcriptome Integration Analysis Reveals the Correlation Between Mesenchymal Stromal Cells and Fibroblasts
title_full_unstemmed Single-Cell Transcriptome Integration Analysis Reveals the Correlation Between Mesenchymal Stromal Cells and Fibroblasts
title_short Single-Cell Transcriptome Integration Analysis Reveals the Correlation Between Mesenchymal Stromal Cells and Fibroblasts
title_sort single-cell transcriptome integration analysis reveals the correlation between mesenchymal stromal cells and fibroblasts
topic Genetics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8961367/
https://www.ncbi.nlm.nih.gov/pubmed/35360851
http://dx.doi.org/10.3389/fgene.2022.798331
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