Spatial heterogeneity of bone marrow endothelial cells unveils a distinct subtype in the epiphysis.
Takahito IgaHiroshi KobayashiDai KusumotoTsukasa SanosakaNobuyuki FujitaIkue Tai-NagaraTomofumi AndoTomoko TakahashiKoichi MatsuoKatsuto HozumiKosei ItoMasatsugu EmaTakeshi MiyamotoMorio MatsumotoMasaya NakamuraHideyuki OkanoShinsuke ShibataJun KohyamaKevin K KimKeiyo TakuboYoshiaki KubotaPublished in: Nature cell biology (2023)
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.
Keyphrases
- bone marrow
- single cell
- endothelial cells
- rna seq
- stem cells
- mesenchymal stem cells
- bone mineral density
- high glucose
- high throughput
- soft tissue
- bone loss
- induced apoptosis
- bone regeneration
- genome wide
- vascular endothelial growth factor
- copy number
- gene expression
- postmenopausal women
- cell cycle arrest
- signaling pathway
- endoplasmic reticulum stress
- cell death
- cell therapy
- case control