Mesenchymal and haematopoietic stem cells form a unique bone marrow niche

被引:2539
作者
Mendez-Ferrer, Simon [1 ,2 ]
Michurina, Tatyana V. [3 ]
Ferraro, Francesca [4 ]
Mazloom, Amin R. [5 ]
MacArthur, Ben D. [5 ]
Lira, Sergio A. [1 ]
Scadden, David T. [4 ]
Ma'ayan, Avi [5 ]
Enikolopov, Grigori N. [3 ]
Frenette, Paul S. [1 ,2 ,6 ]
机构
[1] Mt Sinai Sch Med, Dept Med, New York, NY 10029 USA
[2] Mt Sinai Sch Med, Dept Gene & Cell Med, New York, NY 10029 USA
[3] Cold Spring Harbor Lab, Cold Spring Harbor, NY 11724 USA
[4] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Regenerat Med, Boston, MA 02114 USA
[5] Mt Sinai Sch Med, Dept Pharmacol & Syst Therapeut, New York, NY 10029 USA
[6] Yeshiva Univ Albert Einstein Coll Med, Ruth L & David S Gottesman Inst Stem Cell & Regen, Bronx, NY 10461 USA
基金
美国国家卫生研究院;
关键词
PROGENITOR CELLS; SELF-RENEWAL; NEURAL STEM; EXPRESSION; DIFFERENTIATION; OSTEOPONTIN; OSTEOBLASTS; COOPERATION; RECEPTORS; COMPONENT;
D O I
10.1038/nature09262
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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 beta 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.
引用
收藏
页码:829 / U59
页数:8
相关论文
共 43 条
[31]   Generalized lacZ expression with the ROSA26 Cre reporter strain [J].
Soriano, P .
NATURE GENETICS, 1999, 21 (01) :70-71
[32]  
SOUSA VH, 2009, CEREB CORTEX S1, V19, P1, DOI DOI 10.1093/CERCOR/BHP038
[33]   ISOLATION OF A STEM-CELL FOR NEURONS AND GLIA FROM THE MAMMALIAN NEURAL CREST [J].
STEMPLE, DL ;
ANDERSON, DJ .
CELL, 1992, 71 (06) :973-985
[34]   Osteopontin is a hematopoietic stem cell niche component that negatively regulates stem cell pool size [J].
Stier, S ;
Ko, Y ;
Forkert, F ;
Lutz, C ;
Neuhaus, T ;
Grünewald, E ;
Cheng, T ;
Dombkowski, D ;
Calvi, LM ;
Rittling, SR ;
Scadden, DT .
JOURNAL OF EXPERIMENTAL MEDICINE, 2005, 201 (11) :1781-1791
[35]   Maintenance of the hematopoietic stem cell pool by CXCL12-CXCR4 chemokine signaling in bone marrow stromal cell niches [J].
Sugiyama, Tatsuki ;
Kohara, Hiroshi ;
Noda, Mamiko ;
Nagasawa, Takashi .
IMMUNITY, 2006, 25 (06) :977-988
[36]   Neuroepithelial cells supply an initial transient wave of MSC differentiation [J].
Takashima, Yasuhiro ;
Era, Takumi ;
Nakao, Kazuki ;
Kondo, Saki ;
Kasuga, Masato ;
Smith, Austin G. ;
Nishikawa, Shin-Ichi .
CELL, 2007, 129 (07) :1377-1388
[37]   Disruption of the glucocorticoid receptor gene in the nervous system results in reduced anxiety [J].
Tronche, F ;
Kellendonk, C ;
Kretz, O ;
Gass, P ;
Anlag, K ;
Orban, PC ;
Bock, R ;
Klein, R ;
Schütz, G .
NATURE GENETICS, 1999, 23 (01) :99-103
[38]   Hematopoiesis is severely altered in mice with an induced osteoblast deficiency [J].
Visnjic, D ;
Kalajzic, Z ;
Rowe, DW ;
Katavic, V ;
Lorenzo, J ;
Aguila, HL .
BLOOD, 2004, 103 (09) :3258-3264
[39]   c-Myc controls the balance between hematopoietic stem cell self-renewal and differentiation [J].
Wilson, A ;
Murphy, MJ ;
Oskarsson, T ;
Kaloulis, K ;
Bettess, MD ;
Oser, GM ;
Pasche, AC ;
Knabenhans, C ;
MacDonald, HR ;
Trumpp, A .
GENES & DEVELOPMENT, 2004, 18 (22) :2747-2763
[40]   Detection of functional haematopoietic stem cell niche using real-time imaging [J].
Xie, Yucai ;
Yin, Tong ;
Wiegraebe, Winfried ;
He, Xi C. ;
Miller, Diana ;
Stark, Danny ;
Perko, Katherine ;
Alexander, Richard ;
Schwartz, Joel ;
Grindley, Justin C. ;
Park, Jungeun ;
Haug, Jeff S. ;
Wunderlich, Joshua P. ;
Li, Hua ;
Zhang, Simon ;
Johnson, Teri ;
Feldman, Ricardo A. ;
Li, Linheng .
NATURE, 2009, 457 (7225) :97-U102