Adhesion is prerequisite, but alone insufficient, to elicit stem cell pluripotency
Adhesion is prerequisite, but alone insufficient, to elicit stem cell pluripotency
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DOI：
10.1523/jneurosci.0300-07.2007
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发表时间：
2007-05-16
影响因子：
5.3
通讯作者：
van der Kooy, Derek
中科院分区：
文献类型：
--
作者：
Karpowicz, Phillip;Inoue, Tomoyuki;van der Kooy, Derek
原始哺乳动物神经干细胞（NSC），在胚胎发生的最早阶段，具有多能性在胚胎嵌合体试验中，在成年人中发现的永久NSC相反。我们假设，粘附差异决定了嵌合体检测中干细胞与胚胎细胞的关联，从而决定了它们对后期组织的贡献能力。我们发现，原始神经干细胞和永久神经干细胞具有粘附性差异，导致差异钙粘蛋白表达，导致双分离的结果后，引入到早期与中期妊娠胚胎。原始神经干细胞能够与内细胞团的细胞一起分选，从而有助于早期胚胎发生，而永久性神经干细胞则不能。相反，原始神经干细胞从胚胎第9.5天端脑的细胞中分离出来，并且无法对胚胎中期的神经组织做出贡献，而永久性神经干细胞则可以。通过E-cadherin过表达克服这些粘附差异允许一些确定的NSC整合到内细胞团中，但不足以使它们有助于以后的发育。这些粘合剂的差异表明，在多能神经干细胞在发展过程中不断发展的区室化，并用于说明细胞-细胞协会揭示细胞的贡献的重要性。
Primitive mammalian neural stem cells ( NSCs), arising during the earliest stages of embryogenesis, possess pluripotency in embryo chimera assays in contrast to definitive NSCs found in the adult. We hypothesized that adhesive differences determine the association of stem cells with embryonic cells in chimera assays and hence their ability to contribute to later tissues. We show that primitive NSCs and definitive NSCs possess adhesive differences, resulting from differential cadherin expression, that lead to a double dissociation in outcomes after introduction into the early-versus midgestation embryo. Primitive NSCs are able to sort with the cells of the inner cell mass and thus contribute to early embryogenesis, in contrast to definitive NSCs, which cannot. Conversely, primitive NSCs sort away from cells of the embryonic day 9.5 telencephalon and are unable to contribute to neural tissues at midembryogenesis, in contrast to definitive NSCs, which can. Overcoming these adhesive differences by E-cadherin overexpression allows some definitive NSCs to integrate into the inner cell mass but is insufficient to allow them to contribute to later development. These adhesive differences suggest an evolving compartmentalization in multipotent NSCs during development and serve to illustrate the importance of cell-cell association for revealing cellular contribution.