PMID- 31949165
OWN - NLM
STAT- MEDLINE
DCOM- 20200407
LR  - 20210224
IS  - 2041-1723 (Electronic)
IS  - 2041-1723 (Linking)
VI  - 11
IP  - 1
DP  - 2020 Jan 16
TI  - A Wnt-mediated transformation of the bone marrow stromal cell identity 
      orchestrates skeletal regeneration.
PG  - 332
LID - 10.1038/s41467-019-14029-w [doi]
LID - 332
AB  - 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. beta-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.
FAU - Matsushita, Yuki
AU  - Matsushita Y
AUID- ORCID: 0000-0001-9577-3249
AD  - University of Michigan School of Dentistry, Ann Arbor, MI, 48109, USA.
FAU - Nagata, Mizuki
AU  - Nagata M
AD  - University of Michigan School of Dentistry, Ann Arbor, MI, 48109, USA.
FAU - Kozloff, Kenneth M
AU  - Kozloff KM
AUID- ORCID: 0000-0002-1108-7258
AD  - Department of Orthopaedic Surgery, University of Michigan, Ann Arbor, MI, 48109, 
      USA.
FAU - Welch, Joshua D
AU  - Welch JD
AD  - Department of Computational Medicine and Bioinformatics, Department of Computer 
      Science and Engineering, University of Michigan, Ann Arbor, MI, 48109, USA.
FAU - Mizuhashi, Koji
AU  - Mizuhashi K
AD  - University of Michigan School of Dentistry, Ann Arbor, MI, 48109, USA.
FAU - Tokavanich, Nicha
AU  - Tokavanich N
AD  - University of Michigan School of Dentistry, Ann Arbor, MI, 48109, USA.
FAU - Hallett, Shawn A
AU  - Hallett SA
AD  - University of Michigan School of Dentistry, Ann Arbor, MI, 48109, USA.
FAU - Link, Daniel C
AU  - Link DC
AD  - Washington University School of Medicine, Division of Oncology, St. Louis, MO, 
      63110, USA.
FAU - Nagasawa, Takashi
AU  - Nagasawa T
AD  - Osaka University School of Medicine, Laboratory of Stem Cell Biology and 
      Developmental Immunology, Graduate School of Frontier Biosciences, Suita, Osaka, 
      565-0871, Japan.
FAU - Ono, Wanida
AU  - Ono W
AD  - University of Michigan School of Dentistry, Ann Arbor, MI, 48109, USA.
FAU - Ono, Noriaki
AU  - Ono N
AUID- ORCID: 0000-0002-3771-8230
AD  - University of Michigan School of Dentistry, Ann Arbor, MI, 48109, USA. 
      noriono@umich.edu.
LA  - eng
GR  - R01 DE026666/DE/NIDCR NIH HHS/United States
GR  - P30 AR069620/AR/NIAMS NIH HHS/United States
GR  - P01 CA101937/CA/NCI NIH HHS/United States
GR  - R03 DE027421/DE/NIDCR NIH HHS/United States
GR  - T32 DE007057/DE/NIDCR NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20200116
PL  - England
TA  - Nat Commun
JT  - Nature communications
JID - 101528555
RN  - 0 (Chemokine CXCL12)
RN  - 0 (Cxcl12 protein, mouse)
RN  - 094ZI81Y45 (Tamoxifen)
SB  - IM
MH  - Animals
MH  - Bone Marrow Cells/cytology
MH  - Bone Regeneration/genetics/*physiology
MH  - Bone Remodeling/physiology
MH  - Cell Lineage
MH  - Cell Transdifferentiation
MH  - Chemokine CXCL12/genetics/metabolism
MH  - Male
MH  - Mesenchymal Stem Cells/*metabolism
MH  - Mice
MH  - Mice, Transgenic
MH  - Osteoblasts
MH  - Osteogenesis/genetics/*physiology
MH  - Skeleton/*metabolism
MH  - Stem Cells
MH  - Tamoxifen/pharmacology
MH  - Wnt Signaling Pathway/*physiology
PMC - PMC6965122
COIS- The authors declare no competing interests.
EDAT- 2020/01/18 06:00
MHDA- 2020/04/09 06:00
PMCR- 2020/01/16
CRDT- 2020/01/18 06:00
PHST- 2019/04/27 00:00 [received]
PHST- 2019/12/12 00:00 [accepted]
PHST- 2020/01/18 06:00 [entrez]
PHST- 2020/01/18 06:00 [pubmed]
PHST- 2020/04/09 06:00 [medline]
PHST- 2020/01/16 00:00 [pmc-release]
AID - 10.1038/s41467-019-14029-w [pii]
AID - 14029 [pii]
AID - 10.1038/s41467-019-14029-w [doi]
PST - epublish
SO  - Nat Commun. 2020 Jan 16;11(1):332. doi: 10.1038/s41467-019-14029-w.