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A Postnatal Chondro-Hematopoietic Axis Generates Functional Hematopoietic Stem Cells via Endothelial Transition

ABSTRACT: Conventional understanding holds that definitive hematopoietic stem cells (HSCs) form only during embryogenesis and subsequently colonize bone marrow (BM). We challenge this by identifying a postnatal source of HSCs within the epiphyseal cartilage. Using multimodal fate-mapping, we show that hypertrophic chondrocytes transdifferentiate into vascular endothelial cells. Single-cell RNA sequencing reveals a continuous developmental path from these chondrocyte-derived endothelial cells to HSCs via a hemogenic intermediate. This endothelial-to-hematopoietic transition (EHT) generates functional stem and progenitor cells crucial for initial formation of the secondary BM. The process peaks during early niche assembly and declines upon colonization by external HSCs. Transplantation experiments confirm the cell-autonomous capacity of cartilage to establish a full vascular-hematopoietic niche. Our findings redefine hematopoietic development by revealing a postnatal chondro-hematopoietic axis and an extraordinary plastic potential of chondrocytes.

ORGANISM(S): Mus musculus

PROVIDER: GSE326052 | GEO | 2026/03/31

REPOSITORIES: GEO

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| PRJNA1443220 | ENA

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