Single-cell RNA sequencing analysis of human bone-marrow-derived mesenchymal stem cells and functional subpopulation identification
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Mesenchymal stem cells (MSCs) are a common kind of multipotent cell in vivo, but their heterogeneity limits their further applications. To identify MSC subpopulations and clarify their relationships, we performed cell mapping of bone-marrow-derived MSCs through single-cell RNA (scRNA) sequencing. In our study, three main subpopulations, namely, the stemness subpopulation, functional subpopulation, and proliferative subpopulation, were identified using marker genes and further bioinformatic analyses. Developmental trajectory analysis showed that the stemness subpopulation was the root and then became either the functional subpopulation or the proliferative subpopulation. The functional subpopulation showed stronger immunoregulatory and osteogenic differentiation abilities but lower proliferation and adipogenic differentiation. MSCs at different passages or isolated from different donors exhibited distinct cell mapping profiles, which accounted for their corresponding different functions. This study provides new insight into the biological features and clinical use of MSCs at the single-cell level, which may contribute to expanding their application in the clinic.
Abstract
Mesenchymal stem cells (MSCs) are a common kind of multipotent cell in vivo, but their heterogeneity limits their further applications. To identify MSC subpopulations and clarify their relationships, we performed cell mapping of bone-marrow-derived MSCs through single-cell RNA (scRNA) sequencing. In our study, three main subpopulations, namely, the stemness subpopulation, functional subpopulation, and proliferative subpopulation, were identified using marker genes and further bioinformatic analyses. Developmental trajectory analysis showed that the stemness subpopulation was the root and then became either the functional subpopulation or the proliferative subpopulation. The functional subpopulation showed stronger immunoregulatory and osteogenic differentiation abilities but lower proliferation and adipogenic differentiation. MSCs at different passages or isolated from different donors exhibited distinct cell mapping profiles, which accounted for their corresponding different functions. This study provides new insight into the biological features and clinical use of MSCs at the single-cell level, which may contribute to expanding their application in the clinic.
참고문헌 (37)
- Friedenstein, A. J., "Fibroblast precursors in normal and irradiated mouse hematopoietic organs", Exp. Hematol, 4, pp.267~274 (1976)
- Bianco, P., "“Mesenchymal” stem cells", Annu. Rev. Cell Dev. Biol, 30, pp.677~704 (2014)
- Pittenger, M. F., "Mesenchymal stem cell perspective: cell biology to clinical progress. npj Regen", npj Regen. Med, 4, pp.22~ (2019)
- Stuart, T., "Integrative single-cell analysis", Nat. Rev. Genet, 20, pp.257~272 (2019)
- Xu, Z., "Single-cell RNA sequencing and lipidomics reveal cell and lipid dynamics of fat infiltration in skeletal muscle", J. Cachexia Sarcopenia Muscle, 12, pp.109~129 (2020)
- Crinier, A., "Single-cell profiling reveals the trajectories of natural killer cell differentiation in bone marrow and a stress signature induced by acute myeloid leukemia", Cell. Mol. Immunol, 18, pp.1290~1304 (2020)
- Mehtonen, J., "Single cell characterization of B-lymphoid differentiation and leukemic cell states during chemotherapy in ETV6-RUNX1-positive pediatric leukemia identifies drug-targetable transcription factor activities", Genome Med, 12, pp.99~ (2020)
- Travaglini, K. J., "A molecular cell atlas of the human lung from single-cell RNA sequencing", Nature, 587, pp.619~625 (2020)
- Wen, L., "Single-cell sequencing in stem cell biology", Genome Biol, 17, pp.71~ (2016)
- He, X., "Combination of human umbilical cord mesenchymal stem (stromal)cell transplantation with IFN-gamma treatment synergistically improves the clinical outcomes of patients with rheumatoid arthritis", Ann. Rheum. Dis, 79, pp.1298~1304 (2020)
- Garza, J. R., "Clinical efficacy of intra-articular mesenchymal stromal cells for the treatment of knee osteoarthritis: a double-blinded prospective randomized controlled clinical trial", Am. J. Sports Med, 48, pp.588~598 (2020)
- Levy, M. L., "Phase I", II study of safety and preliminary efficacy of intravenous allogeneic mesenchymal stem cells in chronic stroke, 2019, pp.50, 2835~2841
- Barnhoorn, M. C., "Long-term evaluation of allogeneic bone marrow-derived mesenchymal stromal cell therapy for crohn’s disease perianal fistulas", J. Crohns Colitis, 14, pp.64~70 (2020)
- Rennerfeldt, D. A., "Concise review: when colonies are not clones:evidence and implications of intracolony heterogeneity in mesenchymal stem cells", Stem Cells, 34, pp.1135~1141 (2016)
- Wilson, A., "Nomenclature and heterogeneity : consequences for the use of mesenchymal stem cells in regenerative medicine", Regen. Med, 14, pp.595~611 (2019)
- Wu, C. C., "CD146+ mesenchymal stem cells display greater therapeutic potential than CD146-cells for treating collagen-induced arthritis in mice", Stem Cell Res. Ther, 7, pp.23~ (2016)
- Kawamura, H., "TGF-beta signaling accelerates senescence of human bonederived CD271 and SSEA-4 double-positive mesenchymal stromal cells", Stem Cell Rep, 10, pp.920~932 (2018)
- Huang, Y., "Single cell transcriptomic analysis of human mesenchymal stem cells reveals limited heterogeneity", Cell Death Dis, 10, pp.368~ (2019)
- Liu, S., "Single cell sequencing reveals gene expression signatures associated with bone marrow stromal cell subpopulations and time in culture", J. Transl. Med, 17, pp.23~ (2019)
- Dominici, M., "Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement", Cytotherapy, 8, pp.315~317 (2006)
- Perumalsamy, S., "Chemokine Like Receptor-1(CMKLR-1)Receptor : a potential therapeutic target in management of chemerin induced type 2 diabetes mellitus and cancer", Curr. Pharm. Des, 23, pp.3689~3698 (2017)
- Yoshimura, T., "Chemokine-like receptor 1(CMKLR1)and chemokine(C-C motif)receptor-like 2(CCRL2); two multifunctional receptors with unusual properties", Exp. Cell Res, 317, pp.674~684 (2011)
- Akiyama, K., "Mesenchymal-stem-cell-induced immunoregulation involves FAS-ligand-", FAS-mediated T cell apoptosis, 2012, pp.10, 544~555
- Zhen, G., "Inhibition of TGF-beta signaling in mesenchymal stem cells of subchondral bone attenuates osteoarthritis", Nat. Med, 19, pp.704~712 (2013)
- Hamidouche, Z., "Crosstalks between integrin alpha 5 and IGF2", IGFBP2 signalling trigger human bone marrow-derived mesenchymal stromal osteogenic differentiation, 2010, pp.11, 44~
- Pan, Y., "Long noncoding RNA repressor of adipogenesis negatively regulates the adipogenic differentiation of mesenchymal stem cells through the hnRNP A1-PTX3-ERK axis", Clin. Transl. Med, 10, pp.e227~ (2020)
- Xiang, Q., "Overexpression of Gremlin1 in mesenchymal stem cells improves hindlimb ischemia in mice by enhancing cell survival", J. Cell. Physiol, 232, pp.996~1007 (2017)
- Li, M., "The long noncoding RNA GAS5 negatively regulates the adipogenic differentiation of MSCs by modulating the miR-18a", CTGF axis as a ceRNA, 2018, pp.9, 554~
- Muruganandan, S., "Chemokine-like receptor 1 is a novel wnt target gene that regulates mesenchymal stem cell differentiation", Stem Cells, 35, pp.711~724 (2017)
- Hong, S. H., "Stem cell passage affects directional migration of stem cells in electrotaxis", Stem Cell Res, 38, pp.101475~ (2019)
- Yang, Y. K., "Changes in phenotype and differentiation potential of human mesenchymal stem cells aging in vitro", Stem Cell Res. Ther, 9, pp.131~ (2018)
- Vono, R., "Oxidative stress in mesenchymal stem cell senescence: regulation by coding and noncoding RNAs", Antioxid. Redox Signal, 29, pp.864~879 (2018)
- Li, Y., "Senescence of mesenchymal stem cells(Review)", Int. J. Mol. Med, 39, pp.775~782 (2017)
- Fang, J., "Melatonin prevents senescence of canine adipose-derived mesenchymal stem cells through activating NRF2 and inhibiting ER stress", Aging(Albany NY), 10, pp.2954~2972 (2018)
- Ma, Y., "Autophagy controls mesenchymal stem cell properties and senescence during bone aging", Aging Cell, 17, pp.e12709~ (2018)
- Kim, M., "Donor variation and optimization of human mesenchymal stem cell chondrogenesis in hyaluronic acid", Tissue Eng. Part A, 24, pp.1693~1703 (2018)
- 강인선, "Donor-dependent variation of human umbilical cord blood mesenchymal stem cells in response to hypoxic preconditioning and amelioration of limb ischemia", Experimental and Molecular Medicine, 50, pp.1~15 (2018), 생화학분자생물학회