Single-Cell RNA-Seq of Bone Marrow-Derived Mesenchymal Stem Cells Reveals Unique Profiles of Lineage Priming.
The plasticity and immunomodulatory capacity of mesenchymal stem cells (MSCs) have spurred clinical use in recent years. However, clinical outcomes vary and many ascribe inconsistency to the tissue source of MSCs. Yet unconsidered is the extent of heterogeneity of individual MSCs from a given tissue source with respect to differentiation potential and immune regulatory function. Here we use single-cell RNA-seq to assess the transcriptional diversity of murine mesenchymal stem cells derived from bone marrow. We found genes associated with MSC multipotency were expressed at a high level and with consistency between individual cells. However, genes associated with osteogenic, chondrogenic, adipogenic, neurogenic and vascular smooth muscle differentiation were expressed at widely varying levels between individual cells. Further, certain genes associated with immunomodulation were also inconsistent between individual cells. Differences could not be ascribed to cycles of proliferation, culture bias or other cellular process, which might alter transcript expression in a regular or cyclic pattern. These results support and extend the concept of lineage priming of MSCs and emphasize caution for in vivo or clinical use of MSCs, even when immunomodulation is the goal, since multiple mesodermal (and even perhaps ectodermal) outcomes are a possibility. Purification might enable shifting of the probability of a certain outcome, but is unlikely to remove multilineage potential altogether.
Department of Biomedical Engineering, University of Minnesota, Minneapolis, Minnesota, 55455, United States of America.
Brian T
BT
Freeman
Department of Biomedical Engineering, University of Minnesota, Minneapolis, Minnesota, 55455, United States of America.
Jangwook P
JP
Jung
Department of Biomedical Engineering, University of Minnesota, Minneapolis, Minnesota, 55455, United States of America; Stem Cell Institute, University of Minnesota, Minneapolis, Minnesota, 55455, United States of America; Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota, 55455, United States of America; Lillehei Heart Institute, University of Minnesota, Minneapolis, Minnesota, 55455, United States of America.
Brenda M
BM
Ogle
D000818:Animals; D001854:Bone Marrow Cells / Q000737:chemistry / Q000166:cytology*; D002455:Cell Division; D019070:Cell Lineage; D002478:Cells, Cultured; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D063990:Gene Ontology; D056747:Immunomodulation / Q000235:genetics; D008297:Male; D059630:Mesenchymal Stem Cells / Q000737:chemistry / Q000166:cytology*; D051379:Mice; D008810:Mice, Inbred C57BL; D005810:Multigene Family; D060888:Real-Time Polymerase Chain Reaction; D016415:Sequence Alignment; D017423:Sequence Analysis, RNA / Q000379:methods*; D059010:Single-Cell Analysis / Q000379:methods*; D014158:Transcription, Genetic; D059467:Transcriptome