PT  - JOURNAL ARTICLE
AU  - Jason T. Long
AU  - Abigail Leinroth
AU  - Yihan Liao
AU  - Yinshi Ren
AU  - Anthony J. Mirando
AU  - Tuyet Nguyen
AU  - Wendi Guo
AU  - Deepika Sharma
AU  - Douglas Rouse
AU  - Colleen Wu
AU  - Kathryn Song Eng Cheah
AU  - Courtney M. Karner
AU  - Matthew J. Hilton
TI  - Hypertrophic Chondrocytes Serve as a Reservoir for Marrow Associated Skeletal Stem and Progenitor Cells, Osteoblasts, and Adipocytes During Skeletal Development
AID  - 10.1101/2021.05.18.444731
DP  - 2022 Jan 01
TA  - bioRxiv
PG  - 2021.05.18.444731
4099  - http://biorxiv.org/content/early/2022/01/11/2021.05.18.444731.short
4100  - http://biorxiv.org/content/early/2022/01/11/2021.05.18.444731.full
AB  - Hypertrophic chondrocytes give rise to osteoblasts during skeletal development; however, the process by which these non-mitotic cells make this transition is not well understood. Prior studies have also suggested that skeletal stem and progenitor cells (SSPCs) localize to the surrounding periosteum and serve as a major source of marrow associated SSPCs, osteoblasts, osteocytes, and adipocytes during skeletal development. To further understand the cell transition process by which hypertrophic chondrocytes contribute to osteoblasts or other marrow associated cells, we utilized inducible and constitutive hypertrophic chondrocyte lineage tracing and reporter mouse models (Col10a1CreERT2; R26-tdTomatof/+ and Col10a1Cre; R26-tdTomatof/+) in combination with a PDGFRa-H2B-GFP transgenic line, single cell RNA-sequencing, bulk RNA-sequencing, immunofluorescence staining, and cell transplantation assays. Our data demonstrate that hypertrophic chondrocytes undergo a process of dedifferentiation to generate marrow associated SSPCs that serve as a primary source of osteoblasts during skeletal development. These hypertrophic chondrocyte derived SSPCs commit to a CXCL12-abundant reticular (CAR) cell phenotype during skeletal development and demonstrate unique abilities to recruit vasculature and promote bone marrow establishment, while also contributing to the adipogenic lineage.Competing Interest StatementThe authors have declared no competing interest.