@article{dad1b546e18d46229609683574710c8a,
title = "A Wnt-mediated transformation of the bone marrow stromal cell identity orchestrates skeletal regeneration",
abstract = "Bone marrow stromal cells (BMSCs) are versatile mesenchymal cell populations underpinning the major functions of the skeleton, a majority of which adjoin sinusoidal blood vessels and express C-X-C motif chemokine ligand 12 (CXCL12). However, how these cells are activated during regeneration and facilitate osteogenesis remains largely unknown. Cell-lineage analysis using Cxcl12-creER mice reveals that quiescent Cxcl12-creER+ perisinusoidal BMSCs differentiate into cortical bone osteoblasts solely during regeneration. A combined single cell RNA-seq analysis demonstrate that these cells convert their identity into a skeletal stem cell-like state in response to injury, associated with upregulation of osteoblast-signature genes and activation of canonical Wnt signaling components along the single-cell trajectory. β-catenin deficiency in these cells indeed causes insufficiency in cortical bone regeneration. Therefore, quiescent Cxcl12-creER+ BMSCs transform into osteoblast precursor cells in a manner mediated by canonical Wnt signaling, highlighting a unique mechanism by which dormant stromal cells are enlisted for skeletal regeneration.",
author = "Yuki Matsushita and Mizuki Nagata and Kozloff, {Kenneth M.} and Welch, {Joshua D.} and Koji Mizuhashi and Nicha Tokavanich and Hallett, {Shawn A.} and Link, {Daniel C.} and Takashi Nagasawa and Wanida Ono and Noriaki Ono",
note = "Funding Information: This research was supported by grants from National Institute of Health (R01DE026666 to N.O., R03DE027421 to W.O., P30AR069620 to Michigan Integrated Musculoskeletal Core Center), the Uehara Memorial Foundation Research Fellowship and the Japan Society for the Promotion of Science Overseas Research Fellowship to Y.M. We thank C. Giachelli (University of Washington) for Runx2 floxed mice, M. Pihalja and K. Saiya-Cork of the University of Michigan Flow Cytometry Core, T. Saunders, G. Gavrilina and W. Fillipak of the University of Michigan Transgenic Animal Model Core, T. Tamsen, J. Opp of the University of Michigan Advanced Genomics Core, R. Tagett of the University of Michigan Bioinformatics Core, and C. Stephan, B. Nolan and A. Clark of University of Michigan Medical School Orthopedic Research Laboratories and T. Lau for supporting this study. Publisher Copyright: {\textcopyright} 2020, The Author(s).",
year = "2020",
month = dec,
day = "1",
doi = "10.1038/s41467-019-14029-w",
language = "English",
volume = "11",
journal = "Nature communications",
issn = "2041-1723",
number = "1",
}