Distinct skeletal stem cell types orchestrate long bone skeletogenesis

Elife. 2021 Jul 19:10:e66063. doi: 10.7554/eLife.66063.


Skeletal stem and progenitor cell populations are crucial for bone physiology. Characterization of these cell types remains restricted to heterogenous bulk populations with limited information on whether they are unique or overlap with previously characterized cell types. Here we show, through comprehensive functional and single-cell transcriptomic analyses, that postnatal long bones of mice contain at least two types of bone progenitors with bona fide skeletal stem cell (SSC) characteristics. An early osteochondral SSC (ocSSC) facilitates long bone growth and repair, while a second type, a perivascular SSC (pvSSC), co-emerges with long bone marrow and contributes to shape the hematopoietic stem cell niche and regenerative demand. We establish that pvSSCs, but not ocSSCs, are the origin of bone marrow adipose tissue. Lastly, we also provide insight into residual SSC heterogeneity as well as potential crosstalk between the two spatially distinct cell populations. These findings comprehensively address previously unappreciated shortcomings of SSC research.

Keywords: bone; diversity; mesenchymal stromal cells; mouse; regenerative medicine; skeletal stem cells; stem cells.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adipose Tissue
  • Animals
  • Bone Development*
  • Bone Marrow
  • Bone Marrow Cells
  • Bone and Bones / metabolism*
  • Gene Expression Regulation, Developmental
  • Hematopoietic Stem Cells / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Pericytes
  • Stem Cell Niche
  • Stromal Cells / metabolism*
  • Transcriptome

Associated data

  • GEO/GSE161477