HUMAN HEMATOPOIETIC STEM-CELL ADHERENCE TO CYTOKINES AND MATRIX MOLECULES
HUMAN HEMATOPOIETIC STEM-CELL ADHERENCE TO CYTOKINES AND MATRIX MOLECULES
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DOI：
10.1172/jci115844
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发表时间：
1992-07-01
影响因子：
15.9
通讯作者：
HOFFMAN, R
中科院分区：
文献类型：
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作者：
LONG, MW;BRIDDELL, R;HOFFMAN, R
造血微环境是一个复杂的结构，其中干细胞、祖细胞、基质细胞、生长因子和细胞外基质(ECM)分子相互作用，指导血细胞发育的协调调节。虽然人们对这种微环境的各个组成部分知道得很多，但对这些不同组成部分之间的相互作用，特别是对导致特定发育信号区域本地化的那些相互作用的性质，了解得很少。我们假设细胞因子与细胞外基质分子共同作用，将干细胞固定在微环境中，从而调节其功能。为了分析基质-细胞因子-干细胞的相互作用，我们开发了一个ECM模型系统，其中使用纯化的干细胞群体和塑料固定的单个蛋白质来评估各种基质分子和/或细胞因子在人类造血细胞发育中的作用。对这些相互作用的分析表明，单个ECM蛋白，即凝血酶敏感蛋白，与单个细胞因子(例如，c-kit配体)结合，构成协同调节造血干细胞功能的发育信号。
The hematopoietic microenvironment is a complex structure in which stem cells, progenitor cells, stromal cells, growth factors, and extracellular matrix (ECM) molecules each interact to direct the coordinate regulation of blood cell development. While much is known concerning the individual components of this microenvironment, little is understood of the interactions among these various components or, in particular, the nature of those interactions responsible for the regional localization of specific developmental signals. We hypothesized that cytokines act together with ECM molecules to anchor stem cells within the microenvironment, thus modulating their function. In order to analyze matrix-cytokine-stem cell interactions, we developed an ECM model system in which purified stem cell populations and plastic-immobilized individual proteins are used to assess the role of various matrix molecules and/or cytokines in human hematopoietic cell development. Analysis of these interactions revealed that a single ECM protein, thrombospondin, in conjunction with a single cytokine (e.g., c-kit ligand), constitutes a developmental signal that synergistically modulates hematopoietic stem cell function.