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Mesenchymal and haematopoietic stem cells form a unique bone marrow niche

Mesenchymal and haematopoietic stem cells form a unique bone marrow niche
Mesenchymal and haematopoietic stem cells form a unique bone marrow niche
The cellular constituents forming the haematopoietic stem cell (HSC) niche in the bone marrow are unclear, with studies implicating osteoblasts, endothelial and perivascular cells. Here we demonstrate that mesenchymal stem cells (MSCs), identified using nestin expression, constitute an essential HSC niche component. Nestin+ MSCs contain all the bone-marrow colony-forming-unit fibroblastic activity and can be propagated as non-adherent ‘mesenspheres’ that can self-renew and expand in serial transplantations. Nestin+ MSCs are spatially associated with HSCs and adrenergic nerve fibres, and highly express HSC maintenance genes. These genes, and others triggering osteoblastic differentiation, are selectively downregulated during enforced HSC mobilization or ?3 adrenoreceptor activation. Whereas parathormone administration doubles the number of bone marrow nestin+ cells and favours their osteoblastic differentiation, in vivo nestin+ cell depletion rapidly reduces HSC content in the bone marrow. Purified HSCs home near nestin+ MSCs in the bone marrow of lethally irradiated mice, whereas in vivo nestin+ cell depletion significantly reduces bone marrow homing of haematopoietic progenitors. These results uncover an unprecedented partnership between two distinct somatic stem-cell types and are indicative of a unique niche in the bone marrow made of heterotypic stem-cell pairs
0028-0836
829-834
Méndez-Ferrer, Simón
aacb41d4-d25f-456c-a1d6-aef4d75a8a0a
Michurina, Tatyana V.
77c0aa6b-de07-40af-acc5-e93dc1551789
Ferraro, Francesca
8255a935-ef93-4123-ab73-dd8ac0dedc1e
Mazloom, Amin R.
f3c1191b-2211-4b54-bafc-af8cf3fa47c8
MacArthur, Ben D.
2c0476e7-5d3e-4064-81bb-104e8e88bb6b
Lira, Sergio A.
adfb677b-2849-4b83-b69c-108a23d3b276
Scadden, David T.
1d03ab2d-71c8-42f9-80dc-35ce4ad0012f
Ma’ayan, Avi
49ea105e-cb86-4d59-8655-5456e240dc7e
Enikolopov, Grigori N.
0aaf4b3e-6c3b-4c17-9672-e2e6170947c4
Frenette, Paul S.
0a64d3d2-00d7-4f15-a6ae-8bb56a6f3f24
Méndez-Ferrer, Simón
aacb41d4-d25f-456c-a1d6-aef4d75a8a0a
Michurina, Tatyana V.
77c0aa6b-de07-40af-acc5-e93dc1551789
Ferraro, Francesca
8255a935-ef93-4123-ab73-dd8ac0dedc1e
Mazloom, Amin R.
f3c1191b-2211-4b54-bafc-af8cf3fa47c8
MacArthur, Ben D.
2c0476e7-5d3e-4064-81bb-104e8e88bb6b
Lira, Sergio A.
adfb677b-2849-4b83-b69c-108a23d3b276
Scadden, David T.
1d03ab2d-71c8-42f9-80dc-35ce4ad0012f
Ma’ayan, Avi
49ea105e-cb86-4d59-8655-5456e240dc7e
Enikolopov, Grigori N.
0aaf4b3e-6c3b-4c17-9672-e2e6170947c4
Frenette, Paul S.
0a64d3d2-00d7-4f15-a6ae-8bb56a6f3f24

Méndez-Ferrer, Simón, Michurina, Tatyana V., Ferraro, Francesca, Mazloom, Amin R., MacArthur, Ben D., Lira, Sergio A., Scadden, David T., Ma’ayan, Avi, Enikolopov, Grigori N. and Frenette, Paul S. (2010) Mesenchymal and haematopoietic stem cells form a unique bone marrow niche. Nature, 466 (7308), 829-834. (doi:10.1038/nature09262). (PMID:20703299 )

Record type: Article

Abstract

The cellular constituents forming the haematopoietic stem cell (HSC) niche in the bone marrow are unclear, with studies implicating osteoblasts, endothelial and perivascular cells. Here we demonstrate that mesenchymal stem cells (MSCs), identified using nestin expression, constitute an essential HSC niche component. Nestin+ MSCs contain all the bone-marrow colony-forming-unit fibroblastic activity and can be propagated as non-adherent ‘mesenspheres’ that can self-renew and expand in serial transplantations. Nestin+ MSCs are spatially associated with HSCs and adrenergic nerve fibres, and highly express HSC maintenance genes. These genes, and others triggering osteoblastic differentiation, are selectively downregulated during enforced HSC mobilization or ?3 adrenoreceptor activation. Whereas parathormone administration doubles the number of bone marrow nestin+ cells and favours their osteoblastic differentiation, in vivo nestin+ cell depletion rapidly reduces HSC content in the bone marrow. Purified HSCs home near nestin+ MSCs in the bone marrow of lethally irradiated mice, whereas in vivo nestin+ cell depletion significantly reduces bone marrow homing of haematopoietic progenitors. These results uncover an unprecedented partnership between two distinct somatic stem-cell types and are indicative of a unique niche in the bone marrow made of heterotypic stem-cell pairs

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Published date: August 2010
Organisations: Mathematics

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Local EPrints ID: 175695
URI: https://eprints.soton.ac.uk/id/eprint/175695
ISSN: 0028-0836
PURE UUID: 19b6fb93-8aa5-4ed5-adeb-6a7f826b1382

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Date deposited: 25 Feb 2011 15:07
Last modified: 16 Jul 2019 23:46

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Contributors

Author: Simón Méndez-Ferrer
Author: Tatyana V. Michurina
Author: Francesca Ferraro
Author: Amin R. Mazloom
Author: Sergio A. Lira
Author: David T. Scadden
Author: Avi Ma’ayan
Author: Grigori N. Enikolopov
Author: Paul S. Frenette

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