Molecular Programming of Perivascular Stem Cell Precursors

• Published in: Stem cells (Dayton, Ohio) Vol. 36; no. 12; pp. 1890 - 1904
• Main Authors: Yianni, Val, Sharpe, Paul T.
• Format: Journal Article
• Language: English
• Published: Hoboken, USA John Wiley & Sons, Inc 01.12.2018; Oxford University Press
• Subjects: Adipogenesis; Adult stem cells; Animals; Biocompatibility; Biomedical materials; Bone marrow; Cbfa-1 protein; Cell culture; Cell Differentiation; Chondrogenesis; Chromatin; Dental pulp; Differentiation (biology); Epigenetics; Genes; Histones; Incisors; Insertion; Mesenchymal Stem Cells - metabolism; Mesenchyme; Mice; MSC; Myogenesis; Pericyte; Pericytes; Pericytes - cytology; Pericytes - metabolism; Polycomb group proteins; Populations; Precursors; Stem cell transplantation; Stem cells; Tissues; Transcription; Transcriptomics; Epigenetics; Pericyte; Adult stem cells; MSC; Transcriptomics
• DOI: 10.1002/stem.2895
• ISSN: 1066-5099; 1549-4918

Pericytes have been shown to act as precursors of resident adult stem cells in stromal tissues in vivo. When expanded in vitro these cells are capable of giving rise to multiple mesenchymal cell types, irrespective of their tissue of origin. This phenomenon of multi‐lineage differentiation is only observed in culture, whereas in vivo, stromal stem cell differentiation is restricted to tissue‐specific cell types. An important unanswered question is how a single, widely distributed cell type (a pericyte) gives rise to stem cells with tissue‐specific functions and attributes. Using a combination of transcriptomics and epigenomics we have compared the molecular status of two populations of stromal stem cell precursors. Using a LacZ transgene insertion that is expressed in pericytes but not in stem cells, we were able to compare pericyte populations from two different tissues, mouse incisors and bone marrow. Pericytes, freshly isolated from mouse incisors and bone marrow, exhibited transcriptomes and epigenetic landscapes that were extensively different, reflecting their tissue of origin and future in vivo differentiation potential. Dspp, an odontoblast differentiation gene, as well as additional odontogenic genes, are shown to be expressed in dental pulp‐derived pericytes. These genetic loci are also decorated with histone modifications indicative of a transcriptionally active chromatin state. In bone marrow pericytes, a major osteogenic differentiation gene, Runx2, is not expressed but is marked by both active and repressive histones and therefore primed to be expressed. Polycomb repressor complex 1 analysis showed that key genes involved in the induction of adipogenesis, chondrogenesis, and myogenesis are targeted by Ring1b and therefore stably repressed. This indicates that pericyte populations are molecularly obstructed from differentiating down certain lineages in vivo. Stem Cells 2018;36:1890–15 We isolate fresh pericytes from two anatomical locations and subject them to RNA and histone ChIP sequencing without a prior in vitro expansion step. Molecular profiling of the same cell populations indicate that they harbour epigenetic marks that are driving a dissimilar transcriptomic output, one that is appropriate to the cells tissue of isolation and that restricts the pericytes future differentiation.