PMID- 31809738 OWN - NLM STAT- MEDLINE DCOM- 20200914 LR - 20201207 IS - 1875-9777 (Electronic) IS - 1934-5909 (Print) IS - 1875-9777 (Linking) VI - 25 IP - 6 DP - 2019 Dec 5 TI - Hic1 Defines Quiescent Mesenchymal Progenitor Subpopulations with Distinct Functions and Fates in Skeletal Muscle Regeneration. PG - 797-813.e9 LID - S1934-5909(19)30459-X [pii] LID - 10.1016/j.stem.2019.11.004 [doi] AB - Many adult tissues contain resident stem cells, such as the Pax7(+) satellite cells within skeletal muscle, that regenerate parenchymal elements following damage. Tissue-resident mesenchymal progenitors (MPs) also participate in regeneration, although their function and fate in this process are unclear. Here, we identify Hypermethylated in cancer 1 (Hic1) as a marker of MPs in skeletal muscle and further show that Hic1 deletion leads to MP hyperplasia. Single-cell RNA-seq and ATAC-seq analysis of Hic1(+) MPs in skeletal muscle shows multiple subpopulations, which we further show have distinct functions and lineage potential. Hic1(+) MPs orchestrate multiple aspects of skeletal muscle regeneration by providing stage-specific immunomodulation and trophic and mechanical support. During muscle regeneration, Hic1(+) derivatives directly contribute to several mesenchymal compartments including Col22a1-expressing cells within the myotendinous junction. Collectively, these findings demonstrate that HIC1 regulates MP quiescence and identifies MP subpopulations with transient and enduring roles in muscle regeneration. CI - Copyright (c) 2019 The Authors. Published by Elsevier Inc. All rights reserved. FAU - Scott, R Wilder AU - Scott RW AD - Department of Cellular and Physiological Sciences, 2222 Health Sciences Mall, University of British Columbia, Vancouver, BC, V6T 1Z3, Canada; School of Biomedical Engineering and the Biomedical Research Centre, 2222 Health Sciences Mall, University of British Columbia, Vancouver, BC, V6T 1Z3, Canada. FAU - Arostegui, Martin AU - Arostegui M AD - Department of Cellular and Physiological Sciences, 2222 Health Sciences Mall, University of British Columbia, Vancouver, BC, V6T 1Z3, Canada. FAU - Schweitzer, Ronen AU - Schweitzer R AD - Research Division, Shriners Hospital for Children, Portland, OR 97239, USA. FAU - Rossi, Fabio M V AU - Rossi FMV AD - Department of Medical Genetics, 2222 Health Sciences Mall, University of British Columbia, Vancouver, BC, V6T 1Z3, Canada; School of Biomedical Engineering and the Biomedical Research Centre, 2222 Health Sciences Mall, University of British Columbia, Vancouver, BC, V6T 1Z3, Canada. FAU - Underhill, T Michael AU - Underhill TM AD - Department of Cellular and Physiological Sciences, 2222 Health Sciences Mall, University of British Columbia, Vancouver, BC, V6T 1Z3, Canada; School of Biomedical Engineering and the Biomedical Research Centre, 2222 Health Sciences Mall, University of British Columbia, Vancouver, BC, V6T 1Z3, Canada. Electronic address: tunderhi@brc.ubc.ca. LA - eng GR - U54 CA231652/CA/NCI NIH HHS/United States PT - Journal Article PL - United States TA - Cell Stem Cell JT - Cell stem cell JID - 101311472 RN - 0 (Hic1 protein, mouse) RN - 0 (Kruppel-Like Transcription Factors) SB - IM CIN - Cell Stem Cell. 2020 Feb 6;26(2):129-130. PMID: 32032520 MH - Animals MH - Cell Cycle/genetics/physiology MH - Cell Differentiation/genetics/physiology MH - Cell Proliferation/genetics/physiology MH - Cells, Cultured MH - Female MH - Fluorescent Antibody Technique MH - Kruppel-Like Transcription Factors/genetics/*metabolism MH - Male MH - Mice MH - Muscle, Skeletal/*metabolism/*physiology MH - Regeneration/genetics/*physiology MH - Satellite Cells, Skeletal Muscle/*metabolism MH - Wound Healing/genetics/physiology PMC - PMC6941576 MID - NIHMS1545049 OTO - NOTNLM OT - lineage tracing OT - mesenchymal progenitors OT - myotendinous junction OT - pericytes OT - quiescence OT - scATAC-seq OT - scRNA-seq OT - skeletal muscle OT - tendon OT - tissue regeneration COIS- DECLARATION OF INTERESTS The authors have no competing interests to declare. EDAT- 2019/12/07 06:00 MHDA- 2020/09/15 06:00 PMCR- 2020/12/05 CRDT- 2019/12/07 06:00 PHST- 2019/02/22 00:00 [received] PHST- 2019/07/10 00:00 [revised] PHST- 2019/11/11 00:00 [accepted] PHST- 2019/12/07 06:00 [entrez] PHST- 2019/12/07 06:00 [pubmed] PHST- 2020/09/15 06:00 [medline] PHST- 2020/12/05 00:00 [pmc-release] AID - S1934-5909(19)30459-X [pii] AID - 10.1016/j.stem.2019.11.004 [doi] PST - ppublish SO - Cell Stem Cell. 2019 Dec 5;25(6):797-813.e9. doi: 10.1016/j.stem.2019.11.004.