Hox genes are crucial regulators of periosteal stem cell identity.
Kevin LeclercLindsey H RemarkMalissa RamsukhAnne Marie JosephsonLaura PalmaPaulo E L ParenteMargaux SambonSooyeon LeeEmma Muiños LopezSophie M MorganiPhilipp LeuchtPublished in: Development (Cambridge, England) (2023)
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.
Keyphrases
- stem cells
- transcription factor
- genome wide identification
- genome wide
- cell therapy
- cell proliferation
- dna methylation
- bioinformatics analysis
- genome wide analysis
- long non coding rna
- small molecule
- machine learning
- mesenchymal stem cells
- electronic health record
- copy number
- bone mineral density
- big data
- young adults
- dna binding
- data analysis
- bone regeneration