Journal
STEM CELL REPORTS
Volume 16, Issue 3, Pages 626-640Publisher
CELL PRESS
DOI: 10.1016/j.stemcr.2021.01.011
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Funding
- NIH/NIAMS [NIH1-R01AR071379, NIHR01GM123069]
- American College of Surgeons Clowes Award
- International FOP Association
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The research discovered a specific lineage of cells as ectopic bone progenitors in the zeugopod, providing a new perspective on fate specification and multipotency acquired after injury.
Heterotopic ossification (HO) is a form of pathological cell-fate change of mesenchymal stem/precursor cells (MSCs) that occurs following traumatic injury, limiting range of motion in extremities and causing pain. MSCs have been shown to differentiate to form bone; however, their lineage and aberrant processes after trauma are not well understood. Utilizing a well-established mouse HO model and inducible lineage-tracing mouse (Hoxa11-CreER(T2);ROSA26-LSL-TdTomato), we found that Hoxa11-lineage cells represent HO progenitors specifically in the zeugopod. Bioinformatic single-cell transcriptomic and epigenomic analyses showed Hoxa11-lineage cells are regionally restricted mesenchymal cells that, after injury, gain the potential to undergo differentiation toward chondrocytes, osteoblasts, and adipocytes. This study identifies Hoxa11-lineage cells as zeugopod-specific ectopic bone progenitors and elucidates the fate specification and multipotency that mesenchymal cells acquire after injury. Furthermore, this highlights homeobox patterning genes as useful tools to trace region-specific progenitors and enable location-specific gene deletion.
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