在脏内进行外骨质造血的周围
Christopher N Inra1, Bo O Zhou1, Melih Acar1
1Department of Pediatrics and Children's Research Institute, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA.
Nature
|November 17, 2015
概括
在压力期间,血造干细胞 (HSC) 移动到脏,但其位尚不清楚. 内皮细胞和Tcf21+层细胞形成一个围状,支持外骨质造血 (EMH).
科学领域:
- 血液学
- 干细胞生物学
- 微环境研究
背景情况:
- 造血干细胞 (HSC) 通常存在于骨髓中,但在压力下移动到脏,诱导骨外造血 (EMH).
- 脊髓外血形成的特定细胞组成部分和利基因素在很大程度上仍未被描述.
研究的目的:
- 在EMH期间确定脏微环境中的关键利基因子,干细胞因子 (SCF) 和CXCL12的细胞来源.
- 阐明这些已识别的利基成分在支脏外母细胞形成中的作用.
主要方法:
- 使用由骨髓损伤,失血和怀孕诱导的EMH小鼠模型.
- 在脏中通过免疫组织化学评估内皮细胞和Tcf21+层细胞的SCF和CXCL12表达.
- 通过条件基因删除研究,研究了SCF和CXCL12对EMH和血液形成的必要性.
主要成果:
- 主要表达的SCF是脊髓内皮细胞和Tcf21+侧膜细胞.
- CXCL12是由Tcf21+层细胞的一个子集表达的.
- 诱导EMH导致表达SCF的内皮细胞和层细胞的增殖,HSCs通常在Tcf21+层细胞附近发现.
- 脊髓层细胞中SCF或CXCL12的条件删除,或内皮细胞中的SCF,显著损害EMH和血液细胞数量的减少.
结论:
- 内皮细胞和Tcf21+层细胞协作在脏中建立一个围状EMH.
- 这种脏位对各种造血应激的生理反应至关重要,支持外骨造血.
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