Endothelial and perivascular cells maintain haematopoietic stem cells

By Lei Ding, T. Saunders, G. Enikolopov, S. Morrison. Nature, 2012

1,878 citations recorded by the source corpus.

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 Scfgfp 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.

Subfields: Genetics, Hematology, Immunology

View Paper: https://www.semanticscholar.org/paper/248845edf2889e1b14cccf91252a13e1f2f18335

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Genetics

1. P. Bonaldo
2. F. Gattazzo
3. W. Nauseef
4. A. Urciuolo
5. T. Stappenbeck
6. Melissa A Brown
7. R. Ransohoff

In Hematology

1. W. Nauseef
2. N. Borregaard

In Immunology

1. N. Borregaard
2. W. Nauseef
3. Arturo Zychlinsky
4. C. Rosales
5. V. Papayannopoulos
6. C. Winterbourn
7. Melissa A Brown
8. R. Ransohoff

Citations in the corpus

• Arteriolar niches maintain haematopoietic stem cell quiescence (2013, neutral): “Although Nestin-GFP + cells express high levels of Scf 21 , Nes-cre mediated deletion of Scf has no effect on HSC function 22 .”
• Adipocyte Accumulation in the Bone Marrow during Obesity and Aging Impairs Stem Cell-Based Hematopoietic and Bone Regeneration (2017, background): “…CD45 CD31 Sca1+CD24+ multipotent cells also express the highest levels of Lepr and other prohematopoietic signals, such as Kitl/Scf and Vcam1, and, thus, could represent a further purification step of a mesenchymal stem cell that supports hematopoiesis (Ding et al., 2012; Lewandowski et al., 2010).”
• Extracellular matrix: A dynamic microenvironment for stem cell niche (2014, background): “HSC self-renewal and differentiation are regulated either through contact-dependent signals, such as VCAM-1 [136], or via soluble factors such as SCF [137].”
• Leptin Receptor-expressing mesenchymal stromal cells represent the main source of bone formed by adult bone marrow (2014, neutral): “The observation that Nestin-GFP+ cells included CFU-Fs, but that Nestin-CreER-expressing cells did not (Figures 2C and S1H), is consistent with our observation that different Nestin transgenes exhibit different expression patterns in the bone marrow (Ding et al., 2012).”
• Gremlin 1 Identifies a Skeletal Stem Cell with Bone, Cartilage, and Reticular Stromal Potential (2015, background): “In keeping with previous perisinusoidal lineage-tracing studies, this Nes-creERT line did not generate cartilage or trabecular bone by 6–8 weeks (Ding et al., 2012; Mizoguchi et al., 2014).”