Spatial heterogeneity of bone marrow endothelial cells unveils a distinct subtype in the epiphysis

Takahito Iga, Hiroshi Kobayashi, Dai Kusumoto, Tsukasa Sanosaka, Nobuyuki Fujita, Ikue Tai-Nagara, Tomofumi Ando, Tomoko Takahashi, Koichi Matsuo, Katsuto Hozumi, Kosei Ito, Masatsugu Ema, Takeshi Miyamoto, Morio Matsumoto, Masaya Nakamura, Hideyuki Okano, Shinsuke Shibata, Jun Kohyama, Kevin K. Kim, Keiyo TakuboYoshiaki Kubota

Research output: Contribution to journalArticlepeer-review

3 Citations (Scopus)


Bone marrow endothelial cells (BMECs) play a key role in bone formation and haematopoiesis. Although recent studies uncovered the cellular taxonomy of stromal compartments in the bone marrow (BM), the complexity of BMECs is not fully characterized. In the present study, using single-cell RNA sequencing, we defined a spatial heterogeneity of BMECs and identified a capillary subtype, termed type S (secondary ossification) endothelial cells (ECs), exclusively existing in the epiphysis. Type S ECs possessed unique phenotypic characteristics in terms of structure, plasticity and gene expression profiles. Genetic experiments showed that type S ECs atypically contributed to the acquisition of bone strength by secreting type I collagen, the most abundant bone matrix component. Moreover, these cells formed a distinct reservoir for haematopoietic stem cells. These findings provide the landscape for the cellular architecture in the BM vasculature and underscore the importance of epiphyseal ECs during bone and haematopoietic development.

Original languageEnglish
Pages (from-to)1415-1425
Number of pages11
JournalNature Cell Biology
Issue number10
Publication statusPublished - 10-2023

All Science Journal Classification (ASJC) codes

  • Cell Biology


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