Bergström Tobias, Holmqvist Karin, Tararuk Tatsiana, Johansson Staffan, Forsberg-Nilsson Karin
Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Rudbeck Laboratory, Uppsala University, SE-75185 Uppsala Sweden.
Merck Sharp & Dohme (Sweden) AB, Rotebergsvägen 3, Box 7125, SE-192 07 Sollentuna, Sweden.
Biochim Biophys Acta. 2014 Aug;1840(8):2526-32. doi: 10.1016/j.bbagen.2014.01.021. Epub 2014 Jan 23.
It is becoming increasingly apparent that the extracellular matrix acts as an important regulator of the neural stem niche. Previously we found that neural stem and progenitor cells (NSPCs) derived from the early postnatal subventricular zone of mice adhere to a collagen/hyaluronan hydrogel, whereas NSPCs from the adult and embryonic brain do not.
To examine the specific adhesive properties of young stem cells in more detail, NSPCs isolated from embryonic, postnatal day 6 (P6), and adult mouse brains were cultured on collagen I.
Early postnatal NSPCs formed paxillin-positive focal adhesions on collagen I, and these adhesions could be prevented by an antibody that blocked integrin β1. Furthermore, we found the corresponding integrin alpha subunits α2 and α11 levels to be highest at the postnatal stage. Gene ontology analysis of differentially expressed genes showed higher expression of transcripts involved in vasculature development and morphogenesis in P6 stem cells, compared to adult.
The ability to interact with the extracellular matrix differs between postnatal and adult NSPCs.
Our observations that the specific adhesive properties of early postnatal NSPCs, which are lost in the adult brain, can be ascribed to the integrin subunits expressed by the former furthering our understanding of the developing neurogenic niche. This article is part of a Special Issue entitled Matrix-mediated cell behaviour and properties.
越来越明显的是,细胞外基质作为神经干细胞龛的重要调节因子。此前我们发现,源自小鼠出生后早期脑室下区的神经干细胞和祖细胞(NSPCs)能黏附于胶原蛋白/透明质酸水凝胶,而成年和胚胎脑来源的NSPCs则不能。
为更详细地研究年轻干细胞的特异性黏附特性,将从胚胎、出生后第6天(P6)和成年小鼠脑分离的NSPCs培养在I型胶原蛋白上。
出生后早期的NSPCs在I型胶原蛋白上形成桩蛋白阳性的黏着斑,这些黏着斑可被阻断整合素β1的抗体所抑制。此外,我们发现相应的整合素α亚基α2和α11水平在出生后阶段最高。差异表达基因的基因本体分析显示,与成年NSPCs相比,P6期干细胞中参与血管发育和形态发生的转录本表达更高。
出生后和成年NSPCs与细胞外基质相互作用的能力不同。
我们观察到出生后早期NSPCs的特异性黏附特性(在成体脑中丧失)可归因于前者表达的整合素亚基,这进一步加深了我们对发育中的神经发生龛的理解。本文是名为“基质介导的细胞行为和特性”的特刊的一部分。