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Endothelial and perivascular cells maintain haematopoietic stem cells.

Several cell types have been proposed to create niches for haematopoietic stem cells (HSCs). However, the expression patterns of HSC maintenance factors have not been systematically studied and no such factor has been conditionally deleted from any candidate niche cell. Thus, the cellular sources of these factors are undetermined. Stem cell factor (SCF; also known as KITL) is a key niche component that maintains HSCs. Here, using Scf(gfp) knock-in mice, we found that Scf was primarily expressed by perivascular cells throughout the bone marrow. HSC frequency and function were not affected when Scf was conditionally deleted from haematopoietic cells, osteoblasts, nestin-cre- or nestin-creER-expressing cells. However, HSCs were depleted from bone marrow when Scf was deleted from endothelial cells or leptin receptor (Lepr)-expressing perivascular stromal cells. Most HSCs were lost when Scf was deleted from both endothelial and Lepr-expressing perivascular cells. Thus, HSCs reside in a perivascular niche in which multiple cell types express factors that promote HSC maintenance.

Pubmed ID: 22281595

Authors

  • Ding L
  • Saunders TL
  • Enikolopov G
  • Morrison SJ

Journal

Nature

Publication Data

January 26, 2012

Associated Grants

  • Agency: NHLBI NIH HHS, Id: 5R01HL097760
  • Agency: NIA NIH HHS, Id: R01 AG040209
  • Agency: NHLBI NIH HHS, Id: R01 HL097760
  • Agency: NHLBI NIH HHS, Id: R01 HL097760-04
  • Agency: NIA NIH HHS, Id: R01AG040209
  • Agency: Howard Hughes Medical Institute, Id:
  • Agency: Howard Hughes Medical Institute, Id:

Mesh Terms

  • Alleles
  • Animals
  • Endothelium
  • Gene Knock-In Techniques
  • Hematopoietic Stem Cells
  • Intermediate Filament Proteins
  • Mice
  • Mice, Inbred C57BL
  • Nerve Tissue Proteins
  • Nestin
  • Osteoblasts
  • Pericytes
  • Receptors, Leptin
  • Stem Cell Factor
  • Stem Cell Niche
  • Stromal Cells