Leptin-receptor-expressing mesenchymal stromal cells represent the main source of bone formed by adult bone marrow

Bo O. Zhou; Rui Yue; Malea M. Murphy; James G. Peyer; Sean J. Morrison

doi:10.1016/j.stem.2014.06.008

Leptin-receptor-expressing mesenchymal stromal cells represent the main source of bone formed by adult bone marrow

Bo O. Zhou, Rui Yue, Malea M. Murphy, James G. Peyer, Sean J. Morrison

Research output: Contribution to journal › Article › peer-review

947 Scopus citations

Abstract

Studies of the identity and physiological function of mesenchymal stromal cells (MSCs) have been hampered by a lack of markers that permit both prospective identification and fate mapping in vivo. We found that Leptin Receptor (LepR) is a marker that highly enriches bone marrow MSCs. Approximately 0.3% of bone marrow cells were LepR⁺, 10% of which were CFU-Fs, accounting for 94% of bone marrow CFU-Fs. LepR⁺ cells formed bone, cartilage, and adipocytes in culture and upon transplantation in vivo. LepR ⁺ cells were Scf-GFP⁺, Cxcl12-DsRed^high, and Nestin-GFP^low, markers which also highly enriched CFU-Fs, but negative for Nestin-CreER and NG2-CreER, markers which were unlikely to be found in CFU-Fs. Fate-mapping showed that LepR⁺ cells arose postnatally and gave rise to most bone and adipocytes formed in adult bone marrow, including bone regenerated after irradiation or fracture. LepR⁺ cells were quiescent, but they proliferated after injury. Therefore, LepR⁺ cells are the major source of bone and adipocytes in adult bone marrow.

Original language	English (US)
Pages (from-to)	154-168
Number of pages	15
Journal	Cell Stem Cell
Volume	15
Issue number	2
DOIs	https://doi.org/10.1016/j.stem.2014.06.008
State	Published - Aug 7 2014

ASJC Scopus subject areas

Molecular Medicine
Genetics
Cell Biology

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10.1016/j.stem.2014.06.008

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@article{cf19bc2e894348ad9ff5eebba4fe985e,

title = "Leptin-receptor-expressing mesenchymal stromal cells represent the main source of bone formed by adult bone marrow",

abstract = "Studies of the identity and physiological function of mesenchymal stromal cells (MSCs) have been hampered by a lack of markers that permit both prospective identification and fate mapping in vivo. We found that Leptin Receptor (LepR) is a marker that highly enriches bone marrow MSCs. Approximately 0.3% of bone marrow cells were LepR+, 10% of which were CFU-Fs, accounting for 94% of bone marrow CFU-Fs. LepR+ cells formed bone, cartilage, and adipocytes in culture and upon transplantation in vivo. LepR + cells were Scf-GFP+, Cxcl12-DsRedhigh, and Nestin-GFPlow, markers which also highly enriched CFU-Fs, but negative for Nestin-CreER and NG2-CreER, markers which were unlikely to be found in CFU-Fs. Fate-mapping showed that LepR+ cells arose postnatally and gave rise to most bone and adipocytes formed in adult bone marrow, including bone regenerated after irradiation or fracture. LepR+ cells were quiescent, but they proliferated after injury. Therefore, LepR+ cells are the major source of bone and adipocytes in adult bone marrow.",

author = "Zhou, {Bo O.} and Rui Yue and Murphy, {Malea M.} and Peyer, {James G.} and Morrison, {Sean J.}",

note = "Funding Information: S.J.M. is a Howard Hughes Medical Institute Investigator, the Mary McDermott Cook Chair in Pediatric Genetics, and the director of the Hamon Laboratory for Stem Cells and Cancer. This work was supported by the National Heart, Lung and Blood Institute (HL097760) and the Cancer Prevention and Research Institute of Texas. B.O.Z. was supported by a fellowship from the Leukemia and Lymphoma Society. R.Y. was supported by a fellowship from the Damon Runyon Foundation. J.G.P. was supported by a fellowship from the National Science Foundation. We thank Dr. Hung Luu in Children{\textquoteright}s Medical Center for his expert analysis of hematopoiesis in ossicles and Dr. Aktar Ali in the Mouse Metabolic Phenotyping Core at UT Southwestern for microCT analysis of bone. ",

year = "2014",

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doi = "10.1016/j.stem.2014.06.008",

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AU - Zhou, Bo O.

AU - Yue, Rui

AU - Murphy, Malea M.

AU - Peyer, James G.

AU - Morrison, Sean J.

N1 - Funding Information: S.J.M. is a Howard Hughes Medical Institute Investigator, the Mary McDermott Cook Chair in Pediatric Genetics, and the director of the Hamon Laboratory for Stem Cells and Cancer. This work was supported by the National Heart, Lung and Blood Institute (HL097760) and the Cancer Prevention and Research Institute of Texas. B.O.Z. was supported by a fellowship from the Leukemia and Lymphoma Society. R.Y. was supported by a fellowship from the Damon Runyon Foundation. J.G.P. was supported by a fellowship from the National Science Foundation. We thank Dr. Hung Luu in Children’s Medical Center for his expert analysis of hematopoiesis in ossicles and Dr. Aktar Ali in the Mouse Metabolic Phenotyping Core at UT Southwestern for microCT analysis of bone.

PY - 2014/8/7

Y1 - 2014/8/7

N2 - Studies of the identity and physiological function of mesenchymal stromal cells (MSCs) have been hampered by a lack of markers that permit both prospective identification and fate mapping in vivo. We found that Leptin Receptor (LepR) is a marker that highly enriches bone marrow MSCs. Approximately 0.3% of bone marrow cells were LepR+, 10% of which were CFU-Fs, accounting for 94% of bone marrow CFU-Fs. LepR+ cells formed bone, cartilage, and adipocytes in culture and upon transplantation in vivo. LepR + cells were Scf-GFP+, Cxcl12-DsRedhigh, and Nestin-GFPlow, markers which also highly enriched CFU-Fs, but negative for Nestin-CreER and NG2-CreER, markers which were unlikely to be found in CFU-Fs. Fate-mapping showed that LepR+ cells arose postnatally and gave rise to most bone and adipocytes formed in adult bone marrow, including bone regenerated after irradiation or fracture. LepR+ cells were quiescent, but they proliferated after injury. Therefore, LepR+ cells are the major source of bone and adipocytes in adult bone marrow.

AB - Studies of the identity and physiological function of mesenchymal stromal cells (MSCs) have been hampered by a lack of markers that permit both prospective identification and fate mapping in vivo. We found that Leptin Receptor (LepR) is a marker that highly enriches bone marrow MSCs. Approximately 0.3% of bone marrow cells were LepR+, 10% of which were CFU-Fs, accounting for 94% of bone marrow CFU-Fs. LepR+ cells formed bone, cartilage, and adipocytes in culture and upon transplantation in vivo. LepR + cells were Scf-GFP+, Cxcl12-DsRedhigh, and Nestin-GFPlow, markers which also highly enriched CFU-Fs, but negative for Nestin-CreER and NG2-CreER, markers which were unlikely to be found in CFU-Fs. Fate-mapping showed that LepR+ cells arose postnatally and gave rise to most bone and adipocytes formed in adult bone marrow, including bone regenerated after irradiation or fracture. LepR+ cells were quiescent, but they proliferated after injury. Therefore, LepR+ cells are the major source of bone and adipocytes in adult bone marrow.

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Leptin-receptor-expressing mesenchymal stromal cells represent the main source of bone formed by adult bone marrow

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