Primate embryonic stem cells create their own niche while differentiating in three-dimensional culture systems

Primate embryonic stem cells create their own niche while differentiating in three-dimensional culture systems
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DOI:
10.1111/j.1365-2184.2006.00381.x
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发表时间:
2006-06-01
期刊:
影响因子:
8.5
通讯作者:
Revoltella, RP
Revoltella, RP
中科院分区:
生物学1区
文献类型:
--
作者:
Michelini, M;Franceschini, V;Revoltella, RP

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恒河猴胚胎干细胞 (ESC) (R366.4) 在三维 (3D) 胶原基质上培养,有或没有人新生儿包皮成纤维细胞 (HP1.1) 作为饲养细胞,或嵌入胶原基质中,形成复杂的管状或球形腺样结构,并分化为神经、上皮和内皮谱系特征的表型。在这里,我们分析了内源性细胞外基质(ECM)蛋白、细胞间粘附分子、细胞表面受体、凝集素及其糖配体的产生,通过分化ESC,​​形成一个微环境,一个利基,能够积极影响细胞行为。其中一些分子的表达受到 HP1.1 细胞的调节,而其他分子则不受影响。我们假设可溶性因子和生态位本身对于引导 ESC 在此 3D 环境中的生长和/或分化至关重要。创建这样一个合适的实验3D微环境,并通过ESC进一步修饰并通过外源可溶性因子调节,可以为有关干细胞分化的发育生物学研究中适当的培养系统构成模板。
Rhesus monkey embryonic stem cells (ESCs) (R366.4), cultured on a three-dimensional (3D) collagen matrix with or without human neonatal foreskin fibroblasts (HP1.1) as feeder cells, or embedded in the collagen matrix, formed complex tubular or spherical gland-like structures and differentiated into phenotypes characteristic of neural, epithelial and endothelial lineages. Here, we analysed the production of endogenous extracellular matrix (ECM) proteins, cell-cell adhesion molecules, cell-surface receptors, lectins and their glycoligands, by differentiating ESCs, forming a micro-environment, a niche, able to positively influence cell behaviour. The expression of some of these molecules was modulated by HP1.1 cells while others were unaffected. We hypothesized that both soluble factors and the niche itself were critical in directing growth and/or differentiation of ESCs in this 3D environment. Creating such an appropriate experimental 3D micro-environment, further modified by ESCs and modulated by exogenous soluble factors, may constitute a template for adequate culture systems in developmental biology studies concerning differentiation of stem cells.