PMID- 33651379
OWN - NLM
STAT- MEDLINE
DCOM- 20210809
LR  - 20211122
IS  - 1523-4681 (Electronic)
IS  - 0884-0431 (Print)
IS  - 0884-0431 (Linking)
VI  - 36
IP  - 6
DP  - 2021 Jun
TI  - Intercellular Interactions of an Adipogenic CXCL12-Expressing Stromal Cell Subset 
      in Murine Bone Marrow.
PG  - 1145-1158
LID - 10.1002/jbmr.4282 [doi]
AB  - Bone marrow houses a multifunctional stromal cell population expressing C-X-C 
      motif chemokine ligand 12 (CXCL12), termed CXCL12-abundant reticular (CAR) cells, 
      that regulates osteogenesis and adipogenesis. The quiescent pre-adipocyte-like 
      subset of CXCL12(+) stromal cells ("Adipo-CAR" cells) is localized to sinusoidal 
      surfaces and particularly enriched for hematopoiesis-supporting cytokines. 
      However, detailed characteristics of these CXCL12(+) pre-adipocyte-like stromal 
      cells and how they contribute to marrow adipogenesis remain largely unknown. Here 
      we highlight CXCL12-dependent physical coupling with hematopoietic cells as a 
      potential mechanism regulating the adipogenic potential of CXCL12(+) stromal 
      cells. Single-cell computational analyses of RNA velocity and cell signaling 
      reveal that Adipo-CAR cells exuberantly communicate with hematopoietic cells 
      through CXCL12-CXCR4 ligand-receptor interactions but do not interconvert with 
      Osteo-CAR cells. Consistent with this computational prediction, a substantial 
      fraction of Cxcl12-creER(+) pre-adipocyte-like cells intertwines with 
      hematopoietic cells in vivo and in single-cell preparation in a 
      protease-sensitive manner. Deletion of CXCL12 in these cells using Col2a1-cre 
      leads to a reduction of stromal-hematopoietic coupling and extensive marrow 
      adipogenesis in adult bone marrow, which appears to involve direct conversion of 
      CXCL12(+) cells to lipid-laden marrow adipocytes without altering mesenchymal 
      progenitor cell fates. Therefore, these findings suggest that CXCL12(+) 
      pre-adipocyte-like marrow stromal cells prevent their premature differentiation 
      by maintaining physical coupling with hematopoietic cells in a CXCL12-dependent 
      manner, highlighting a possible cell-non-autonomous mechanism that regulates 
      marrow adipogenesis. (c) 2021 American Society for Bone and Mineral Research 
      (ASBMR).
CI  - (c) 2021 American Society for Bone and Mineral Research (ASBMR).
FAU - Matsushita, Yuki
AU  - Matsushita Y
AD  - University of Michigan School of Dentistry, Ann Arbor, MI, USA.
FAU - Chu, Angel Ka Yan
AU  - Chu AKY
AD  - Department of Computational Medicine and Bioinformatics, Department of Computer 
      Science and Engineering, University of Michigan, Ann Arbor, MI, USA.
FAU - Ono, Wanida
AU  - Ono W
AD  - University of Michigan School of Dentistry, Ann Arbor, MI, 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, USA.
FAU - Ono, Noriaki
AU  - Ono N
AUID- ORCID: 0000-0002-3771-8230
AD  - University of Michigan School of Dentistry, Ann Arbor, MI, USA.
LA  - eng
GR  - R01 DE029181/DE/NIDCR NIH HHS/United States
GR  - R01 HG010883/HG/NHGRI NIH HHS/United States
GR  - R01 DE026666/DE/NIDCR NIH HHS/United States
GR  - R03 DE027421/DE/NIDCR NIH HHS/United States
GR  - R01 DE030630/DE/NIDCR NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20210316
PL  - England
TA  - J Bone Miner Res
JT  - Journal of bone and mineral research : the official journal of the American 
      Society for Bone and Mineral Research
JID - 8610640
RN  - 0 (Chemokine CXCL12)
SB  - IM
MH  - *Adipogenesis
MH  - Animals
MH  - Bone Marrow
MH  - Bone Marrow Cells
MH  - Cell Differentiation
MH  - Chemokine CXCL12
MH  - Hematopoietic Stem Cells
MH  - *Mesenchymal Stem Cells
MH  - Mice
MH  - Stromal Cells
PMC - PMC8605623
MID - NIHMS1750249
OTO - NOTNLM
OT  - BONE-FAT INTERACTIONS
OT  - GENETIC ANIMAL MODELS
OT  - PRECLINICAL STUDIES
OT  - STROMAL/STEM CELLS
COIS- Disclosures All authors state that they have no conflicts of interest.
EDAT- 2021/03/03 06:00
MHDA- 2021/08/10 06:00
PMCR- 2021/11/20
CRDT- 2021/03/02 12:16
PHST- 2021/01/08 00:00 [revised]
PHST- 2020/09/16 00:00 [received]
PHST- 2021/02/24 00:00 [accepted]
PHST- 2021/03/03 06:00 [pubmed]
PHST- 2021/08/10 06:00 [medline]
PHST- 2021/03/02 12:16 [entrez]
PHST- 2021/11/20 00:00 [pmc-release]
AID - 10.1002/jbmr.4282 [doi]
PST - ppublish
SO  - J Bone Miner Res. 2021 Jun;36(6):1145-1158. doi: 10.1002/jbmr.4282. Epub 2021 Mar 
      16.