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Hoxb5标志着长期的造血干细胞,并显示出一个均的周围细胞
James Y Chen1,2, Masanori Miyanishi1,2, Sean K Wang1,2
1Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, California 94305, USA.
Nature
|February 12, 2016
概括
研究人员确定homeobox B5 (Hoxb5) 是标记小鼠长期造血干细胞 (HSC) 的关键基因. 表达Hoxb5的HSC表现出优异的长期溶解能力,揭示了更精确的方法来识别这些关键的干细胞.
科学领域:
- 干细胞生物学
- 血液形成
- 分子遗传学
背景情况:
- 造血干细胞 (HSC) 对于血液形成至关重要,并且已被广泛研究.
- 目前用于隔离HSC的方法依赖于复杂的多参数流细胞计,识别表型子集.
- 在干细胞研究中,了解HSC异质性和精确识别仍然是一个挑战.
研究的目的:
- 通过无偏见的查来确定长期HSC (LT-HSC) 的单个基因标志物.
- 在移植模型中验证基因标记HSC的功能能力.
- 在骨髓内研究LT-HSCs的体内定位.
主要方法:
- 无偏见的多步查,以确定在LT-HSC中表达的基因.
- 开发一个Hoxb5-reporter小鼠模型 (tri-mCherry) 来跟踪Hoxb5的表达.
- 在初级和二级接受者中进行竞争性移植测定.
- 在鼠标骨髓的现场成像以确定LT-HSC的定位.
主要成果:
- 鉴定出Homeobox B5 (Hoxb5) 是一种在小鼠LT-HSC中独特表达的基因.
- 在体内,表达Hoxb5的HSC表现出强大的长期造血复制.
- 在之前定义的HSC种群中,很大一部分人缺乏LT-HSC潜力.
- 超过94%的Hoxb5 ((+) LT-HSC被发现附着在骨髓中的VE-cadherin ((+) 细胞上,这表明它们位于骨髓周围.
结论:
- Hoxb5 是用于识别小鼠LT-HSC的可靠分子标记物.
- 周围血管空间是小鼠骨髓中LT-HSC的主要位.
- 这一发现完善了HSC识别,并提供了对HSC定位和利基互动的见解.
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