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首页> 外文期刊>Journal of Cellular Physiology >Diverse isoforms of colony-stimulating factor-1 have different effects on the development of stroma-dependent hematopoietic cells.
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Diverse isoforms of colony-stimulating factor-1 have different effects on the development of stroma-dependent hematopoietic cells.

机译:不同亚型的集落刺激因子- 1的发展有不同的影响吗stroma-dependent造血细胞。

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摘要

Maintenance and differentiation of hematopoietic stem and progenitor cells are controlled by complex interactions with the stroma microenvironment. Stroma-cell interactions can be supported by locally expressed membrane-spanning cell-surface (cs) growth factors. CSF-1 is expressed by stroma as a soluble glycoprotein, as proteoglycan, or as a membrane-spanning cs glycoprotein. CSF-1 regulates the survival, proliferation, and differentiation of mononuclear phagocytes. Whereas the biological role of soluble CSF-1 is well characterized, the function of the membrane-spanning cell-surface CSF-1 (csCSF-1) remains unclear. To analyze the biological significance of csCSF-1 in vitro, we used an epithelial cell line to ectopically express the different CSF-1 isoforms. In co-cultures of CSF-1 transduced epithelial cells with primary, early hematopoietic progenitor cells we examined whether interaction between csCSF-1 and its receptor mediates cell proliferation, self-renewal, or differentiation. csCSF-1 induces long-lasting proliferation of stimulated cells and furthermore supports self-renewal. Ectopic secretion of soluble CSF-1 does not permit long-term growth of progenitor cells but induces differentiation of monocytes into macrophages. Previously, we showed that the soluble and cs isoforms of stroma-encoded SCF differently affect the development of hematopoietic cells. Cell-surface SCF (csSCF) promotes self-renewal of stimulated cells whereas soluble SCF causes clonal extinction. These results and those presented here for CSF-1 provide evidence for diverse functions of the isoforms of the ligands SCF and CSF-1 for two tyrosine kinase receptors of the subclass III both regulating hematopoiesis on stroma.
机译:维护和造血分化干细胞和祖细胞的控制与基质复杂的交互微环境。支持本地membrane-spanning表示细胞表面(cs)的生长因子。间质表达的可溶性糖蛋白,蛋白多糖,或者作为membrane-spanning cs糖蛋白。单核细胞的增殖和分化吞噬细胞。可溶性CSF-1特点,函数membrane-spanning细胞表面CSF-1(csCSF-1)仍不清楚。csCSF-1体外生物学意义,我们使用ectopically上皮细胞系表达不同的CSF-1亚型。CSF-1转导上皮细胞的共培养主,早期造血祖我们检查是否相互作用细胞csCSF-1及其受体介导细胞增殖、自我更新或分化。csCSF-1引发持久的扩散刺激细胞,而且支持自我更新。不允许长期增长的祖但细胞诱导分化的单核细胞为巨噬细胞。现金流量表的可溶性和c亚型stroma-encoded以不同的方式影响的发展造血细胞。促进自我更新而刺激的细胞可溶性自洽场导致克隆灭绝。结果,那些CSF-1这里介绍多样化的功能提供依据亚型的配体自洽场和CSF-1两酪氨酸激酶受体子类三世两个调节造血基质。

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