福克斯c1是血造干细胞/原始细胞利基形成的关键调节者
Yoshiki Omatsu1, Masanari Seike1, Tatsuki Sugiyama1
11] Department of Immunobiology and Hematology, Institute for Frontier Medical Sciences, Kyoto University, Japan [2] Japan Science and Technology Agency (JST), Core Research for Evolutional Science and Technology (CREST), 53 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan.
Nature
|March 5, 2014
概括
转录因子Foxc1对于维持骨髓中的造血干细胞处至关重要. 删除Foxc1会破坏的形成,减少干细胞,并促进骨髓中的脂肪积累.
科学领域:
- 血液学 血液学 血液学
- 干细胞生物学 干细胞生物学
- 发育生物学 发展生物学
背景情况:
- 造血干细胞和原始细胞 (HSPCs) 位于骨髓的特殊中.
- 介酶原体,包括CXCL12丰富的网状细胞 (CAR),是关键的利基成分.
- 调节利基形成的分子机制仍然不完全理解.
研究的目的:
- 研究转录因子Foxc1在介质干细胞的发展和维护中的作用.
- 阐明利基形成的分子基础及其对HSPC监管的影响.
主要方法:
- 在小鼠骨髓中利用了Foxc1的遗传删除模型 (胚胎和可诱导).
- 分析了骨髓细胞性,脂肪生成和关键利基因素的表达 (CXCL12,SCF).
- 评估了造血干细胞和原始细胞种群及其在体内维护.
主要成果:
- 福克斯c1优先表达在CAR细胞中,这对于HSPC维护至关重要.
- 删除Foxc1导致HSPCs减少,骨质母细胞正常,但脂肪细胞增加 (黄髓).
- 在成年人中,诱导性缺失减少了HSPCs和减少了CXCL12/SCF,但没有导致黄髓.
结论:
- 福克斯c1是介酶的发展和维护的关键调节者.
- 福克斯c1抑制CAR原始体内的脂肪生成,并促进利基因素的表达.
- 对于HSPCs来说,Foxc1对于骨髓利基的结构和功能完整性至关重要.
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