The homeostasis of hematopoietic stern and progenitor cells (HSC) in the bone marrow is regulated by a complex interplay of exogenous signals, including extracellular matrix (ECM) molecules, cell-cell contacts, and cytokines. To investigate the influence of spatial restriction and adhesive interactions on HSC fate decisions, we prepared a set of fibronectin-coated micrometer-sized cavities. Analysis of human CD133 + HSCs isolated after culture on these surfaces revealed that proliferation and differentiation is decreased when HSCs are supported by substrates with small microcavities. Single cell analysis of adherent cells also revealed decreased DNA synthesis and higher levels of HSC marker expression inside the smaller cavities. Increasing the cytokine concentration highlighted the tight balance of adhesion related signals and soluble cues acting on HSC fate decisions. Our results suggest that confining human HSCs in ECM-coated microcavities is a possible method to maintain these cells in a quiescent and immature state, an important advantage for several HSC applications.
机构:
Hokkaido Univ, Grad Sch Engn, Div Mol Chem, Kita Ku, Sapporo, Hokkaido 0608628, JapanHokkaido Univ, Grad Sch Engn, Div Mol Chem, Kita Ku, Sapporo, Hokkaido 0608628, Japan
机构:Indiana Univ, Sch Med,James Whitcomb Riley Hosp Children, Herman B Wells Ctr Pediat Res,Dept Pediat, Hematol Oncol Sect, Indianapolis, IN 46202 USA
van der Loo, JCM
;
Xiao, XL
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机构:Indiana Univ, Sch Med,James Whitcomb Riley Hosp Children, Herman B Wells Ctr Pediat Res,Dept Pediat, Hematol Oncol Sect, Indianapolis, IN 46202 USA
Xiao, XL
;
McMillin, D
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机构:Indiana Univ, Sch Med,James Whitcomb Riley Hosp Children, Herman B Wells Ctr Pediat Res,Dept Pediat, Hematol Oncol Sect, Indianapolis, IN 46202 USA
McMillin, D
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Hashino, K
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机构:Indiana Univ, Sch Med,James Whitcomb Riley Hosp Children, Herman B Wells Ctr Pediat Res,Dept Pediat, Hematol Oncol Sect, Indianapolis, IN 46202 USA
Hashino, K
;
Kato, I
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机构:Indiana Univ, Sch Med,James Whitcomb Riley Hosp Children, Herman B Wells Ctr Pediat Res,Dept Pediat, Hematol Oncol Sect, Indianapolis, IN 46202 USA
Kato, I
;
Williams, DA
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机构:
Indiana Univ, Sch Med, Howard Hughes Med Inst, Indianapolis, IN 46202 USAIndiana Univ, Sch Med,James Whitcomb Riley Hosp Children, Herman B Wells Ctr Pediat Res,Dept Pediat, Hematol Oncol Sect, Indianapolis, IN 46202 USA
机构:
Hokkaido Univ, Grad Sch Engn, Div Mol Chem, Kita Ku, Sapporo, Hokkaido 0608628, JapanHokkaido Univ, Grad Sch Engn, Div Mol Chem, Kita Ku, Sapporo, Hokkaido 0608628, Japan
机构:Indiana Univ, Sch Med,James Whitcomb Riley Hosp Children, Herman B Wells Ctr Pediat Res,Dept Pediat, Hematol Oncol Sect, Indianapolis, IN 46202 USA
van der Loo, JCM
;
Xiao, XL
论文数: 0引用数: 0
h-index: 0
机构:Indiana Univ, Sch Med,James Whitcomb Riley Hosp Children, Herman B Wells Ctr Pediat Res,Dept Pediat, Hematol Oncol Sect, Indianapolis, IN 46202 USA
Xiao, XL
;
McMillin, D
论文数: 0引用数: 0
h-index: 0
机构:Indiana Univ, Sch Med,James Whitcomb Riley Hosp Children, Herman B Wells Ctr Pediat Res,Dept Pediat, Hematol Oncol Sect, Indianapolis, IN 46202 USA
McMillin, D
;
Hashino, K
论文数: 0引用数: 0
h-index: 0
机构:Indiana Univ, Sch Med,James Whitcomb Riley Hosp Children, Herman B Wells Ctr Pediat Res,Dept Pediat, Hematol Oncol Sect, Indianapolis, IN 46202 USA
Hashino, K
;
Kato, I
论文数: 0引用数: 0
h-index: 0
机构:Indiana Univ, Sch Med,James Whitcomb Riley Hosp Children, Herman B Wells Ctr Pediat Res,Dept Pediat, Hematol Oncol Sect, Indianapolis, IN 46202 USA
Kato, I
;
Williams, DA
论文数: 0引用数: 0
h-index: 0
机构:
Indiana Univ, Sch Med, Howard Hughes Med Inst, Indianapolis, IN 46202 USAIndiana Univ, Sch Med,James Whitcomb Riley Hosp Children, Herman B Wells Ctr Pediat Res,Dept Pediat, Hematol Oncol Sect, Indianapolis, IN 46202 USA