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Deneen Wellik, Professor and Chair, Cell & Regenerative Biology, ” Hox function in musculoskeletal development, maintenance and regeneration”
February 26 @ 12:00 pm - 1:00 pm
Topic: Hox function in musculoskeletal development, maintenance and regeneration
Abstract: Multipotent mesenchymal stromal cells (MSCs) are required to support 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 Hoxa11-CreERT2 lineage-tracing system, we show Hoxa11-lineage marked cells give rise to all skeletal lineages throughout the life of the animal. Further, Hoxa11-lineage marked cells persist as life-long skeletal MSCs, including those from embryonic stages. Our studies establish that Hox-expressing cells specifically enrich for life-long, skeletal stem cells arising from the earliest stages of skeletal development. Further, conditional loss-of-function Hox11 at postnatal and adult stages demonstrate a continued function for these genes in skeletal growth and homeostasis, establishing Hox genes as life-long regulators of the skeleton, not only as developmental patterning regulators. In novel preliminary work, we are also exploring new and surprising roles for these genes in postnatal growth and homeostasis of muscle tissue.