Hox genes are crucial regulators of periosteal stem cell identity.

Autor:	Leclerc K; Department of Orthopedic Surgery, NYU Robert I. Grossman School of Medicine, New York, NY 10016, USA., Remark LH; Department of Orthopedic Surgery, NYU Robert I. Grossman School of Medicine, New York, NY 10016, USA.; Department of Cell Biology, NYU Robert I. Grossman School of Medicine, New York, NY 10016, USA., Ramsukh M; Department of Orthopedic Surgery, NYU Robert I. Grossman School of Medicine, New York, NY 10016, USA., Josephson AM; Department of Orthopedic Surgery, NYU Robert I. Grossman School of Medicine, New York, NY 10016, USA.; Department of Cell Biology, NYU Robert I. Grossman School of Medicine, New York, NY 10016, USA., Palma L; Department of Orthopedic Surgery, NYU Robert I. Grossman School of Medicine, New York, NY 10016, USA., Parente PEL; Department of Orthopedic Surgery, NYU Robert I. Grossman School of Medicine, New York, NY 10016, USA., Sambon M; Department of Orthopedic Surgery, NYU Robert I. Grossman School of Medicine, New York, NY 10016, USA., Lee S; Department of Orthopedic Surgery, NYU Robert I. Grossman School of Medicine, New York, NY 10016, USA.; Institute of Comparative Molecular Endocrinology, Ulm University, Ulm 89081, Germany., Lopez EM; Department of Orthopedic Surgery, NYU Robert I. Grossman School of Medicine, New York, NY 10016, USA.; Cell Therapy Area, Clínica Universidad de Navarra, Pamplona 31008, Spain., Morgani SM; Department of Orthopedic Surgery, NYU Robert I. Grossman School of Medicine, New York, NY 10016, USA., Leucht P; Department of Orthopedic Surgery, NYU Robert I. Grossman School of Medicine, New York, NY 10016, USA.; Department of Cell Biology, NYU Robert I. Grossman School of Medicine, New York, NY 10016, USA.
Jazyk:	angličtina
Zdroj:	Development (Cambridge, England) [Development] 2023 Mar 15; Vol. 150 (6). Date of Electronic Publication: 2023 Mar 24.
DOI:	10.1242/dev.201391
Abstrakt:	Periosteal stem and progenitor cells (PSPCs) are major contributors to bone maintenance and repair. Deciphering the molecular mechanisms that regulate their function is crucial for the successful generation and application of future therapeutics. Here, we pinpoint Hox transcription factors as necessary and sufficient for periosteal stem cell function. Hox genes are transcriptionally enriched in periosteal stem cells and their overexpression in more committed progenitors drives reprogramming to a naïve, self-renewing stem cell-like state. Crucially, individual Hox family members are expressed in a location-specific manner and their stem cell-promoting activity is only observed when the Hox gene is matched to the anatomical origin of the PSPC, demonstrating a role for the embryonic Hox code in adult stem cells. Finally, we demonstrate that Hoxa10 overexpression partially restores the age-related decline in fracture repair. Together, our data highlight the importance of Hox genes as key regulators of PSPC identity in skeletal homeostasis and repair. Competing Interests: Competing interests The authors declare no competing or financial interests. (© 2023. Published by The Company of Biologists Ltd.)
Databáze:	MEDLINE
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