Journal
NATURE COMMUNICATIONS
Volume 10, Issue -, Pages -Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/s41467-019-11100-4
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Funding
- National Cancer Institute of the National Institutes of Health [P30CA046592]
- National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institute of Health (NIH) [R01 AR061402]
- National Institute of Dental and Craniofacial Research of the NIH [T32 DE007057]
- National Institute of Child Health and Human Development of the NIH [T32 HD007505]
- Warner-Lambert Fellowship from University of Michigan Cellular and Molecular Biology training program
- University of Michigan Cell and Developmental Biology Bradley M. Patten Fellowship
- Michigan Integrative Musculoskeletal Health Core Center [P30 AR069620]
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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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