Endothelial and perivascular cells maintain haematopoietic stem cells
- PMID: 22281595
- PMCID: PMC3270376
- DOI: 10.1038/nature10783
Endothelial and perivascular cells maintain haematopoietic stem cells
Abstract
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.
Conflict of interest statement
The authors declare no competing financial interests.
Figures
![Figure 1](https://cdn.statically.io/img/www.ncbi.nlm.nih.gov/pmc/articles/instance/3270376/bin/nihms343810f1.gif)
![Figure 2](https://cdn.statically.io/img/www.ncbi.nlm.nih.gov/pmc/articles/instance/3270376/bin/nihms343810f2.gif)
![Figure 3](https://cdn.statically.io/img/www.ncbi.nlm.nih.gov/pmc/articles/instance/3270376/bin/nihms343810f3.gif)
![Figure 4](https://cdn.statically.io/img/www.ncbi.nlm.nih.gov/pmc/articles/instance/3270376/bin/nihms343810f4.gif)
![Figure 5](https://cdn.statically.io/img/www.ncbi.nlm.nih.gov/pmc/articles/instance/3270376/bin/nihms343810f5.gif)
Comment in
-
Stem cells: The right neighbour.Nature. 2012 Jan 25;481(7382):453-5. doi: 10.1038/481453a. Nature. 2012. PMID: 22281591 No abstract available.
-
This niche is a maze; an amazing niche.Cell Stem Cell. 2013 Apr 4;12(4):391-2. doi: 10.1016/j.stem.2013.03.012. Cell Stem Cell. 2013. PMID: 23561440 Free PMC article.
Similar articles
-
Haematopoietic stem cells and early lymphoid progenitors occupy distinct bone marrow niches.Nature. 2013 Mar 14;495(7440):231-5. doi: 10.1038/nature11885. Epub 2013 Feb 24. Nature. 2013. PMID: 23434755 Free PMC article.
-
Mesenchymal and haematopoietic stem cells form a unique bone marrow niche.Nature. 2010 Aug 12;466(7308):829-34. doi: 10.1038/nature09262. Nature. 2010. PMID: 20703299 Free PMC article.
-
CXCL12 in early mesenchymal progenitors is required for haematopoietic stem-cell maintenance.Nature. 2013 Mar 14;495(7440):227-30. doi: 10.1038/nature11926. Epub 2013 Feb 24. Nature. 2013. PMID: 23434756 Free PMC article.
-
[Bone and Stem Cells. Bone marrow microenvironment niches for hematopoietic stem and progenitor cells].Clin Calcium. 2014 Apr;24(4):517-26. Clin Calcium. 2014. PMID: 24681497 Review. Japanese.
-
Niches for hematopoietic stem cells and immune cell progenitors.Int Immunol. 2019 Feb 6;31(1):5-11. doi: 10.1093/intimm/dxy058. Int Immunol. 2019. PMID: 30169696 Review.
Cited by
-
SenNet recommendations for detecting senescent cells in different tissues.Nat Rev Mol Cell Biol. 2024 Jun 3. doi: 10.1038/s41580-024-00738-8. Online ahead of print. Nat Rev Mol Cell Biol. 2024. PMID: 38831121 Review.
-
Ecological insights into hematopoiesis regulation: unraveling the influence of gut microbiota.Gut Microbes. 2024 Jan-Dec;16(1):2350784. doi: 10.1080/19490976.2024.2350784. Epub 2024 May 10. Gut Microbes. 2024. PMID: 38727219 Free PMC article. Review.
-
Establishment of human hematopoietic organoids for evaluation of hematopoietic injury and regeneration effect.Stem Cell Res Ther. 2024 May 4;15(1):133. doi: 10.1186/s13287-024-03743-y. Stem Cell Res Ther. 2024. PMID: 38704588 Free PMC article.
-
Advances in hematopoietic stem cells ex vivo expansion associated with bone marrow niche.Ann Hematol. 2024 Apr 30. doi: 10.1007/s00277-024-05773-1. Online ahead of print. Ann Hematol. 2024. PMID: 38684510 Review.
-
Thrombopoietin mimetic stimulates bone marrow vascular and stromal niches to mitigate acute radiation syndrome.Stem Cell Res Ther. 2024 Apr 29;15(1):123. doi: 10.1186/s13287-024-03734-z. Stem Cell Res Ther. 2024. PMID: 38679747 Free PMC article.
References
-
- Kiel MJ, Morrison SJ. Uncertainty in the niches that maintain haematopoietic stem cells. Nat Rev Immunol. 2008;8:290–301. - PubMed
-
- Wilson A, Trumpp A. Bone-marrow haematopoietic-stem-cell niches. Nat Rev Immunol. 2006;6:93–106. - PubMed
-
- Arai F, et al. Tie2/angiopoietin-1 signaling regulates hematopoietic stem cell quiescence in the bone marrow niche. Cell. 2004;118:149–161. - PubMed
-
- Calvi LM, et al. Osteoblastic cells regulate the haematopoietic stem cell niche. Nature. 2003;425:841–846. - PubMed
Publication types
MeSH terms
Substances
Associated data
- Actions
Grants and funding
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical
Molecular Biology Databases
Miscellaneous