Arteriolar niches maintain haematopoietic stem cell quiescence

Arteriolar niches maintain haematopoietic stem cell quiescence

2013 October 31 | Yuya Kunisaki, Ingmar Bruns, Christoph Scheiermann, Jalal Ahmed, Sandra Pinho, Dachuan Zhang, Toshihide Mizoguchi, Qiaozi Wei, Daniel Lucas, Keisuke Ito, Jessica C. Mar, Aviv Bergman, and Paul S. Frenette
A critical niche for maintaining haematopoietic stem cell (HSC) quiescence is found in small arterioles within the bone marrow (BM). These arterioles are surrounded by rare NG2⁺ pericytes, distinct from LepR⁺ cells associated with sinusoids. Activation of HSCs leads to their migration from NG2⁺ periarteriolar niches to LepR⁺ perisinusoidal niches. Conditional depletion of NG2⁺ cells results in increased HSC cycling and reduced functional long-term repopulating HSCs in BM, indicating that arteriolar niches are essential for maintaining HSC quiescence. HSCs are significantly associated with small arterioles in the BM, which are distinct from sinusoids. These arterioles are surrounded by Nestin⁺ perivascular cells, which are divided into two subtypes: Nes-GFP⁺ bright cells (Nesperi) and Nes-GFP⁺ dim cells (Nesretic). Nesperi cells are associated with arterioles and are quiescent, while Nesretic cells are associated with sinusoids and are more proliferative. Nesperi cells express genes related to the HSC niche and are protected from myeloablation, whereas Nesretic cells are more susceptible. HSC quiescence is associated with localization in vascular niches, particularly arterioles. HSCs in close proximity to Nesperi cells are more likely to be quiescent, as shown by label-retaining assays and Ki-67 staining. HSCs are also more likely to be quiescent near osteoblasts, but not significantly associated with Col2.3-GFP⁺ cells, indicating that arterioles are a key niche for HSC quiescence. NG2⁺ Nesperi cells promote HSC quiescence and are essential for HSC maintenance in the BM. Depletion of NG2⁺ cells leads to increased HSC cycling and reduced HSC numbers in the BM, indicating their critical role in maintaining HSC quiescence. These findings suggest that arterioles provide a niche that maintains HSC quiescence and protects them from genotoxic insults. The study highlights the importance of distinct vascular niches in maintaining HSC quiescence and proliferation. Arterioles and sinusoids provide different microenvironments that regulate HSC behavior. The findings have implications for understanding stem cell fate in health and cancer, as well as for developing strategies to protect HSCs from damage.A critical niche for maintaining haematopoietic stem cell (HSC) quiescence is found in small arterioles within the bone marrow (BM). These arterioles are surrounded by rare NG2⁺ pericytes, distinct from LepR⁺ cells associated with sinusoids. Activation of HSCs leads to their migration from NG2⁺ periarteriolar niches to LepR⁺ perisinusoidal niches. Conditional depletion of NG2⁺ cells results in increased HSC cycling and reduced functional long-term repopulating HSCs in BM, indicating that arteriolar niches are essential for maintaining HSC quiescence. HSCs are significantly associated with small arterioles in the BM, which are distinct from sinusoids. These arterioles are surrounded by Nestin⁺ perivascular cells, which are divided into two subtypes: Nes-GFP⁺ bright cells (Nesperi) and Nes-GFP⁺ dim cells (Nesretic). Nesperi cells are associated with arterioles and are quiescent, while Nesretic cells are associated with sinusoids and are more proliferative. Nesperi cells express genes related to the HSC niche and are protected from myeloablation, whereas Nesretic cells are more susceptible. HSC quiescence is associated with localization in vascular niches, particularly arterioles. HSCs in close proximity to Nesperi cells are more likely to be quiescent, as shown by label-retaining assays and Ki-67 staining. HSCs are also more likely to be quiescent near osteoblasts, but not significantly associated with Col2.3-GFP⁺ cells, indicating that arterioles are a key niche for HSC quiescence. NG2⁺ Nesperi cells promote HSC quiescence and are essential for HSC maintenance in the BM. Depletion of NG2⁺ cells leads to increased HSC cycling and reduced HSC numbers in the BM, indicating their critical role in maintaining HSC quiescence. These findings suggest that arterioles provide a niche that maintains HSC quiescence and protects them from genotoxic insults. The study highlights the importance of distinct vascular niches in maintaining HSC quiescence and proliferation. Arterioles and sinusoids provide different microenvironments that regulate HSC behavior. The findings have implications for understanding stem cell fate in health and cancer, as well as for developing strategies to protect HSCs from damage.
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