Age-dependent modulation of vascular niches for haematopoietic stem cells

Kusumbe, Anjali P.Max Planck Inst Mol Biomed, Dept Tissue Morphogenesis, D-48149 Munster, Germany.;Univ Munster, Fac Med, D-48149 Munster, Germany. (author)

Blood vessels define local microenvironments in the skeletal system, play crucial roles in osteogenesis and provide niches for haematopoietic stem cells(1-6). The properties of nicheforming vessels and their changes in the ageing organism remain incompletely understood. Here we show that Notch signalling in endothelial cells leads to the expansion of haematopoietic stem cell niches in bone, which involves increases in CD31-positive capillaries and platelet-derived growth factor receptor-beta (PDGFR beta)-positive perivascular cells, arteriole formation and elevated levels of cellular stem cell factor. Although endothelial hypoxia-inducible factor signalling promotes some of these changes, it fails to enhance vascular niche function because of a lack of arterialization and expansion of PDGFR beta-positive cells. In ageing mice, niche-forming vessels in the skeletal system are strongly reduced but can be restored by activation of endothelial Notch signalling. These findings indicate that vascular niches for haematopoietic stem cells are part of complex, age-dependent microenvironments involving multiple cell populations and vessel subtypes.

Ramasamy, Saravana K.Max Planck Inst Mol Biomed, Dept Tissue Morphogenesis, D-48149 Munster, Germany.;Univ Munster, Fac Med, D-48149 Munster, Germany. (author)
Itkin, TomerWeizmann Inst Sci, Dept Immunol, IL-76100 Rehovot, Israel. (author)
Mae, Maarja AndaloussiUppsala universitet,Institutionen för immunologi, genetik och patologi (author)
Langen, Urs H.Max Planck Inst Mol Biomed, Dept Tissue Morphogenesis, D-48149 Munster, Germany.;Univ Munster, Fac Med, D-48149 Munster, Germany. (author)
Betsholtz, ChristerKarolinska Institutet,Uppsala universitet,Vaskulärbiologi(Swepub:uu)chbet517 (author)
Lapidot, TsveeWeizmann Inst Sci, Dept Immunol, IL-76100 Rehovot, Israel. (author)
Adams, Ralf H.Max Planck Inst Mol Biomed, Dept Tissue Morphogenesis, D-48149 Munster, Germany.;Univ Munster, Fac Med, D-48149 Munster, Germany. (author)
Max Planck Inst Mol Biomed, Dept Tissue Morphogenesis, D-48149 Munster, Germany.;Univ Munster, Fac Med, D-48149 Munster, Germany.Weizmann Inst Sci, Dept Immunol, IL-76100 Rehovot, Israel. (creator_code:org_t)

In:Nature: Springer Science and Business Media LLC532:7599, s. 380-+0028-08361476-4687

By the author/editor: Kusumbe, Anjali ...; Ramasamy, Sarava ...; Itkin, Tomer; Mae, Maarja Anda ...; Langen, Urs H.; Betsholtz, Chris ...; show more...; Lapidot, Tsvee; Adams, Ralf H.; show less...

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MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Medical Biotechn ...; and Medical Biotechn ...

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