A role for the Wnt gene family in hematopoiesis: Expansion of multilineage progenitor cells
A role for the Wnt gene family in hematopoiesis: Expansion of multilineage progenitor cells
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DOI：
10.1182/blood.v89.10.3624.3624_3624_3635
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发表时间：
1997-05-15
期刊：
影响因子：
20.3
通讯作者：
Matthews, W
中科院分区：
文献类型：
--
作者：
Austin, TW;Solar, GP;Matthews, W
微环境是造血干细胞 (HSC) 的关键调节因子，也是控制干细胞命运的细胞外因子的可能来源。对这些微环境因素的更好理解可能来自对发育细胞命运决定的研究，其中显示了多电位调用的细胞间相互作用的关键作用。 Wnt 基因家族已知可调节多种组织中多能细胞的细胞命运和细胞间相互作用，通过逆转录酶-聚合酶链式反应检查了造血组织中由果蝇卷曲基因的鼠同源物编码的 Wnt 及其推定受体的表达，Wnt-5a 和 Wnt-10b 在第 11 天的鼠卵黄中表达 囊、第 14 天胎儿肝脏和胎儿肝脏 AA4(+) 细胞。四种小鼠卷曲同源物 Mfz3-7 的表达谱与 Wnt-5a 和 Wnt-10b 几乎相同，值得注意的是，Wnt-10b 在胎肝 AA4(+) Sca(+) c-kit(+) (flASK) HSC 群体中表达，通过用可溶性 WNT 处理培养物中的 HSC 群体来研究 Wnt 在 HSC 命运决定中的作用 相对于对照培养基，将转染 Wnt-1、Wnt-5a 或 Wnt-10b cDNA 的细胞的条件培养基添加到 flASK 细胞培养物中，分别刺激细胞数量增加 7 倍、8 倍和 11 倍。通过免疫耗竭从该培养基中去除 WNT-5a 会耗尽培养基的刺激活性，而添加部分纯化的 WNT-5a 会刺激细胞数量增加。 相对于对照细胞扩增五倍，用带有 Wnt-5a cDNA 的逆转录病毒转导 flASK 细胞增强增殖，我们得出结论，WNT 刺激造血祖细胞的存活/增殖，证明 WNT 包含一类新型造血细胞调节剂。 (C) 1997 年，美国血液学会。
The microenvironment is a key regulator of hematopoietic stem cells (HSCs) and is a likely source of extracellular factors that control stem cell fate. A better understanding of these microenvironmental factors may come from investigations of developmental cell fate determination in which the critical roles of cell-cell interactions of multipotential calls have been shown. The Wnt gene family is known to regulate the cell fate and cell-cell interactions df multipotential cells in a variety of tissues, Expression of Wnts and of their putative receptors encoded by murine homologs of the Drosophila frizzled gene in hematopoietic tissues was examined by reverse transcriptase-polymerase chain reaction, Wnt-5a and Wnt-10b were expressed in day-11 murine yolk sac, day-14 fetal liver, and fetal liver AA4(+) cells. The expression profiles of four murine frizzled homologs, Mfz3-7, were nearly identical to that of Wnt-5a and Wnt-10b, Notably, Wnt-10b was expressed in the fetal liver AA4(+) Sca(+) c-kit(+) (flASK) HSC population, A role for Wnts in HSC fate determination was studied by treatment of HSC populations in culture with soluble WNT proteins, The addition of conditioned media from cells transfected with Wnt-1, Wnt-5a, or Wnt-10b cDNAs to cultures of flASK cells stimulated a sevenfold, eightfold, and 11 fold expansion in cell number, respectively, relative to control media, Removal of WNT-5a from this media by immunodepletion depleted the stimulatory activity from the media, whereas addition of a partially purified WNT-5a stimulated a fivefold expansion relative to control cells, Transduction of flASK cells with a retrovirus bearing a Wnt-5a cDNA enhanced proliferation, We conclude that WNTs stimulate the survival/proliferation of hematopoietic progenitors, demonstrating that WNTs comprise a novel class of hematopoietic cell regulators. (C) 1997 by The American Society of Hematology.