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Nat Commun. 2019 Jul 18;10(1):3168. doi: 10.1038/s41467-019-11100-4.

Hox11 expressing regional skeletal stem cells are progenitors for osteoblasts, chondrocytes and adipocytes throughout life.

Author information

1
Department of Cell & Regenerative Biology, University of Wisconsin-Madison, Madison, WI, 53705, USA.
2
Cellular and Molecular Biology Program, University of Michigan, Ann Arbor, MI, 48109-2200, USA.
3
Department of Orthopedic Surgery, University of Michigan, Ann Arbor, MI, 48109-2200, USA.
4
Division of Experimental Hematology and Cancer Research, Cincinnati Children's Medical Center, Cincinnati, OH, 45229-2842, USA.
5
Department of Cell & Regenerative Biology, University of Wisconsin-Madison, Madison, WI, 53705, USA. wellik@wisc.edu.

Abstract

Multipotent mesenchymal stromal cells (MSCs) are required for skeletal formation, maintenance, and repair throughout life; however, current models posit that postnatally arising long-lived adult MSCs replace transient embryonic progenitor populations. We previously reported exclusive expression and function of the embryonic patterning transcription factor, Hoxa11, in adult skeletal progenitor-enriched MSCs. Here, using a newly generated Hoxa11-CreERT2 lineage-tracing system, we show Hoxa11-lineage marked cells give rise to all skeletal lineages throughout the life of the animal and persist as MSCs. Hoxa11 lineage-positive cells give rise to previously described progenitor-enriched MSC populations marked by LepR-Cre and Osx-CreER, placing them upstream of these populations. Our studies establish that Hox-expressing cells are skeletal stem cells that arise from the earliest stages of skeletal development and self-renew throughout the life of the animal.

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