Hematopoietic stem cell arrival triggers dynamic remodeling of the perivascular niche.

Hematopoietic stem cell arrival triggers dynamic remodeling of the perivascular niche.
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DOI:
10.1016/j.cell.2014.12.032
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发表时间:
2015-01-15
期刊:
影响因子:
64.5
通讯作者:
Zon LI
Zon LI
中科院分区:
生物学1区
文献类型:
--
作者:
Tamplin OJ;Durand EM;Carr LA;Childs SJ;Hagedorn EJ;Li P;Yzaguirre AD;Speck NA;Zon LI

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造血干细胞和祖细胞(HSPCs)可以重建和维持整个血液系统。我们在斑马鱼中产生了高特异性的HSPCs转基因报告基因。这使我们能够对内源性HSPCs进行高分辨率实时成像,目前在哺乳动物骨髓中不可能。利用这一系统,我们发现了单个HSPCs与其生态位之间明显的相互作用。当HSPC到达血管周围生态位时,一组内皮细胞重塑形成周围的袋。这种结构在小鼠胎儿肝脏中似乎是保守的。相关光镜和电镜显示内皮细胞围绕单个HSPC连接单个间充质间质细胞。实时成像显示间充质间质细胞锚定HSPCs并定向其分裂。化学基因筛选发现,化合物石蒜碱在发育过程中促进hspc -生态位相互作用,并最终将干细胞库扩展到成年期。我们的研究为干细胞定植的动态生态位相互作用提供了证据。
Hematopoietic stem and progenitor cells (HSPCs) can reconstitute and sustain the entire blood system. We generated a highly specific transgenic reporter of HSPCs in zebrafish. This allowed us to perform high-resolution live imaging on endogenous HSPCs not currently possible in mammalian bone marrow. Using this system we have uncovered distinct interactions between single HSPCs and their niche. When an HSPC arrives in the perivascular niche, a group of endothelial cells remodel to form a surrounding pocket. This structure appears conserved in mouse fetal liver. Correlative light and electron microscopy revealed that endothelial cells surround a single HSPC attached to a single mesenchymal stromal cell. Live imaging showed mesenchymal stromal cells anchor HSPCs and orient their divisions. A chemical genetic screen found the compound lycorine promotes HSPC-niche interactions during development and ultimately expands the stem cell pool into adulthood. Our studies provide evidence for dynamic niche interactions upon stem cell colonization.
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