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早期介质细胞前代体中CXCL12是血液形成干细胞维护所需的

Adam Greenbaum¹, Yen-Michael S Hsu, Ryan B Day

¹Department of Medicine, Washington University School of Medicine, St Louis, Missouri 63110, USA.

|February 26, 2013

概括

骨髓中的流体细胞形成了支造血干细胞 (HSC) 和它们的祖先的. 来自包括内皮细胞和介质细胞原生体在内的特定树皮细胞的CXCL12信号传递对HSC的维护和功能至关重要.

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
骨髓的微环境骨髓的微环境

背景情况:

造血干细胞 (HSC) 存在于骨髓中,由树皮细胞调节.
包括骨质母细胞和周血管细胞在内的各种 stromal 细胞类型都涉及到 HSC 的维护.
对于独特的造血原生细胞 (HPC) 子集的特定和调节分子仍然不清楚.

研究的目的:

为了研究CXCL12信号从特定的树皮细胞种群调节HSCs和HPCs中的作用.
为了确定不同的树叶是否支持特定的HPC子集.

主要方法:

使用遗传模型 (例如,Prx1-cre) 从候选树皮细胞群中选择性删除Cxcl12.
描述HPCs,包括HSCs,淋巴细胞原始体,以及它们的长期再生活动和静止.
对HPC调动和骨髓保留的分析.

主要成果:

从矿化骨质母细胞中删除Cxcl12对HSC或淋巴细胞前体没有影响.
从母表达性树皮细胞中删除Cxcl12,导致HPC调动和B-淋巴细胞原体的损失,但正常的HSC功能.
从内皮细胞中删除Cxcl12导致HSC长期重复活动的适度损失.
从尼斯阴性介质原体中Cxcl12的删除导致了显著的HSC丧失,重新繁殖活动,静止和常见的淋巴原体.

结论:

奥斯特里克斯表达的树皮细胞形成了一个独特的利基,支持B-淋巴细胞的祖先,并保留HPCs.
周脉层细胞,包括内皮细胞和介质细胞前代细胞的CXCL12表达对HSC支持至关重要.
这些发现阐明了不同层层在调节血造干细胞和前细胞群中的特殊作用.

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