Endothelium-derived stromal cells contribute to hematopoietic bone marrow niche formation

Cell Stem Cell. 2021 Apr 1;28(4):653-670.e11. doi: 10.1016/j.stem.2021.01.006. Epub 2021 Feb 8.


Bone marrow stromal cells (BMSCs) play pivotal roles in tissue maintenance and regeneration. Their origins, however, remain incompletely understood. Here we identify rare LNGFR+ cells in human fetal and regenerative bone marrow that co-express endothelial and stromal markers. This endothelial subpopulation displays transcriptional reprogramming consistent with endothelial-to-mesenchymal transition (EndoMT) and can generate multipotent stromal cells that reconstitute the bone marrow (BM) niche upon transplantation. Single-cell transcriptomics and lineage tracing in mice confirm robust and sustained contributions of EndoMT to bone precursor and hematopoietic niche pools. Interleukin-33 (IL-33) is overexpressed in subsets of EndoMT cells and drives this conversion process through ST2 receptor signaling. These data reveal generation of tissue-forming BMSCs from mouse and human endothelial cells and may be instructive for approaches to human tissue regeneration.

Keywords: EndoMT; development; endothelial; endothelial-mesenchymal transition; hematopoietic stem cell; mesenchymal; niche; regeneration; stroma; transdifferentiation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bone Marrow Cells
  • Bone Marrow*
  • Endothelial Cells
  • Endothelium
  • Hematopoietic Stem Cell Transplantation*
  • Hematopoietic Stem Cells
  • Mice
  • Stromal Cells