@article{23b18e978a2e4b60869c9668e9299924,
title = "Bone marrow and periosteal skeletal stem/progenitor cells make distinct contributions to bone maintenance and repair",
abstract = "A fundamental question in bone biology concerns the contributions of skeletal stem/progenitor cells (SSCs) in the bone marrow versus the periosteum to bone repair. We found that SSCs in adult bone marrow can be identified based on Leprcre and Adiponectin-cre/creER expression while SSCs in adult periosteum can be identified based on Gli1creERT2 expression. Under steady-state conditions, new bone arose primarily from bone marrow SSCs. After bone injuries, both SSC populations began proliferating but made very different contributions to bone repair. Drill injuries were primarily repaired by LepR+/Adiponectin+ bone marrow SSCs. Conversely, bicortical fractures were primarily repaired by Gli1+ periosteal SSCs, though LepR+/Adiponectin+ bone marrow cells transiently formed trabecular bone at the fracture site. Gli1+ periosteal cells also regenerated LepR+ bone marrow stromal cells that expressed hematopoietic niche factors at fracture sites. Different bone injuries are thus repaired by different SSCs, with periosteal cells regenerating bone and marrow stroma after non-stabilized fractures.",
keywords = "bicortical fracture, endosteal, Leptin receptor, periosteal, skeletal stem cell",
author = "Jeffery, {Elise C.} and Mann, {Terry L.A.} and Pool, {Jade A.} and Zhiyu Zhao and Morrison, {Sean J.}",
note = "Funding Information: S.J.M. is a Howard Hughes Medical Institute (HHMI) investigator, the Mary McDermott Cook Chair in Pediatric Genetics, the Kathryn and Gene Bishop Distinguished Chair in Pediatric Research, the director of the Hamon Laboratory for Stem Cells and Cancer, and a Cancer Prevention and Research Institute of Texas Scholar. This work was supported partly by the Josephine Hughes Sterling Foundation. E.C.J. was supported by a postdoctoral fellowship from the Damon Runyon Cancer Research Foundation (2278-16). We thank B. Levi and R. Zondervan for use of their bone fracture apparatus. We thank N. Loof, T. Shih, and C. Cantu of the Moody Foundation Flow Cytometry Facility, as well as the BioHPC high performance computing cloud at UTSW for computational resources. We also thank M. Mettlen and K. Luby-Phelps of the Quantitative Light Microscopy Core Facility at UT Southwestern Medical Center. We thank S.J. Conway for Periostin-cre mice and Y. Wan for CathepsinKcre mice. This article is subject to HHMI's Open Access to Publications policy. HHMI lab heads have previously granted a nonexclusive CC BY 4.0 license to the public and a sublicensable license to HHMI in their research articles. Pursuant to those licenses, the author-accepted manuscript of this article can be made freely available under a CC BY 4.0 license immediately upon publication. E.C.J. and S.J.M. conceived the project, designed, and interpreted experiments. E.C.J. performed most of the experiments, with technical assistance from T.L.A.M. and J.A.P. Z.Z. analyzed single-cell RNA sequencing data and assisted with statistical analyses. E.C.J. and S.J.M. wrote the manuscript. The authors declare no competing interests. Funding Information: S.J.M. is a Howard Hughes Medical Institute (HHMI) investigator, the Mary McDermott Cook Chair in Pediatric Genetics, the Kathryn and Gene Bishop Distinguished Chair in Pediatric Research, the director of the Hamon Laboratory for Stem Cells and Cancer, and a Cancer Prevention and Research Institute of Texas Scholar. This work was supported partly by the Josephine Hughes Sterling Foundation. E.C.J. was supported by a postdoctoral fellowship from the Damon Runyon Cancer Research Foundation ( 2278-16 ). We thank B. Levi and R. Zondervan for use of their bone fracture apparatus. We thank N. Loof, T. Shih, and C. Cantu of the Moody Foundation Flow Cytometry Facility, as well as the BioHPC high performance computing cloud at UTSW for computational resources. We also thank M. Mettlen and K. Luby-Phelps of the Quantitative Light Microscopy Core Facility at UT Southwestern Medical Center. We thank S.J. Conway for Periostin-cre mice and Y. Wan for CathepsinK cre mice. This article is subject to HHMI{\textquoteright}s Open Access to Publications policy. HHMI lab heads have previously granted a nonexclusive CC BY 4.0 license to the public and a sublicensable license to HHMI in their research articles. Pursuant to those licenses, the author-accepted manuscript of this article can be made freely available under a CC BY 4.0 license immediately upon publication. Publisher Copyright: {\textcopyright} 2022 The Authors",
year = "2022",
month = nov,
day = "3",
doi = "10.1016/j.stem.2022.10.002",
language = "English (US)",
volume = "29",
pages = "1547--1561.e6",
journal = "Cell Stem Cell",
issn = "1934-5909",
publisher = "Cell Press",
number = "11",
}