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2017-04-06 发布于江苏
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3组 Mesenchymal and haematopoietic stem cells form a unique.pdf

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3组 Mesenchymal and haematopoietic stem cells form a unique

Mesenchymal and haematopoietic stem cells form a unique bone marrow niche Simón Méndez-Ferrer1,2,?, Tatyana V. Michurina3, Francesca Ferraro4, Amin R. Mazloom5, Ben D. MacArthur5,?, Sergio A. Lira1, David T. Scadden4, Avi Ma’ayan5, Grigori N. Enikolopov3, and Paul S. Frenette1,2,6 1Department of Medicine, Mount Sinai School of Medicine, New York, New York 10029, USA. 2Department of Gene and Cell Medicine, Mount Sinai School of Medicine, New York, New York 10029, USA. 3Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, USA. 4Center for Regenerative Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114, USA. 5Department of Pharmacology and Systems Therapeutics, Mount Sinai School of Medicine, New York, New York 10029, USA. 6Ruth L. and David S. Gottesman Institute for Stem Cell and Regenerative Medicine Research, Albert Einstein College of Medicine, Bronx, New York 10461, USA. 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 β3 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+ ? 2010 Macm