In vivo reactivation of a quiescent cell population located in the ocular ciliary body of adult mammals
In vivo reactivation of a quiescent cell population located in the ocular ciliary body of adult mammals
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DOI：
10.1016/j.exer.2005.11.016
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发表时间：
2006-07-01
影响因子：
3.4
通讯作者：
Bernier, Gilbert
中科院分区：
文献类型：
--
作者：
Abdouh, Mohamed;Bernier, Gilbert
从成年哺乳动物的眼睫状体(CB)中分离出了罕见的具有干细胞特征的静止细胞。在体外，成人视网膜干细胞被报道能产生含有多能视网膜前体细胞的球状克隆。能否在体内刺激这些干细胞群的增殖以产生新的视网膜细胞是一个重要的问题。在此，我们报道了在生长因子(GF)刺激下，脐带血中静止的细胞群在体内重新激活。GF刺激可使一部分CB上皮细胞重新获得胚胎特征(Nestin)，并表达细胞周期进入标记Cyclin D1和Ki67。这种诱导效应在神经视网膜中没有观察到。经GF激活的CB上皮细胞共表达视网膜祖细胞同源域转录因子Pax6和Chx10。溴脱氧尿嘧啶核苷(BrdU)掺入实验表明，连续注射GF可引起CB内细胞团的新生增殖，且呈剂量依赖关系。对单个细胞簇内BrdU含量的分析表明，细胞分裂模式主要是不对称的。细胞增殖不是由CB或视网膜损伤引起的，这表明没有TUNEL标记的细胞。新产生的细胞不会迁移到视网膜，也不会分化为视网膜神经元。这项研究表明，在体内注射GF后，具有视网膜干/祖细胞特征的静止细胞群的增殖可以重新激活，并表明，在成年哺乳动物中，CB是细胞迁移和神经发生的不允许环境。(C)2006爱思唯尔有限公司。保留所有权利。
Rare quiescent cells with stem cell characteristics have been isolated from the ocular ciliary body (CB) of adult mammals. In vitro, adult retinal stem cells were reported to generate sphere colonies containing multipotent retinal progenitor cells. Whether proliferation of this stem cell population can be stimulated in vivo in order to generate new retinal cells is an important issue. Herein we report on the in vivo reactivation of a quiescent cell population present in the CB upon growth factors (GF) stimulation. GF stimulation resulted in the re-acquisition of embryonic characteristics (Nestin) and expression of the cell cycle entry markers CyclinD1 and Ki67 by a subset of CB epithelial cells. This inductive effect was not observed in the neural retina. GF-activated CB epithelial cells co-express the retinal progenitor homeodomain transcription factors Pax6 and Chx10. Serial GF injections led to do novo proliferation of clusters of cells in the CB, in a dose-dependent manner, as revealed by bromodeoxyuridine (BrdU) incorporation. Analysis of cells' BrdU content within individual clusters suggests a mode of cell division that is predominantly asymmetric. Cell proliferation was not induced by CB or retinal damage, as indicated by the absence of TUNEL-labeled cells. Newly produced cells did not migrate into the retina nor did they differentiate into retinal neurons. This study demonstrates that proliferation of a quiescent cell population with retinal stem/progenitor cell characteristics can be reactivated in vivo upon GF injections and suggests that, in adult mammals, the CB is a non-permissive environment for cell migration and neurogenesis. (c) 2006 Elsevier Ltd. All rights reserved.