Regulation of prenatal human retinal neurosphere growth and cell fate potential by retinal pigment epithelium and Mash1.
Regulation of prenatal human retinal neurosphere growth and cell fate potential by retinal pigment epithelium and Mash1.
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DOI：
10.1634/stemcells.2008-0300
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发表时间：
2008-12
期刊：
影响因子：
--
通讯作者：
Svendsen CN
中科院分区：
文献类型：
--
作者：
Gamm DM;Wright LS;Capowski EE;Shearer RL;Meyer JS;Kim HJ;Schneider BL;Melvan JN;Svendsen CN
在中枢神经系统的发育过程中，干细胞和祖细胞的增殖和分化受到复杂的细胞间和细胞内相互作用的控制，这些相互作用协调特定细胞类型的精确时空产生。在胚胎视网膜内，祖细胞位于视网膜色素上皮（RPE）附近，其在神经感觉视网膜之前分化，并且具有分泌多种生长因子的能力。我们发现，人产前RPE条件培养基（RPE CM）中分泌的蛋白质因子延长并增强了人产前视网膜神经球的生长。RPE CM的促生长活性是促分裂原依赖性的，并且与转录因子磷酸化的急性增加相关。RPE CM处理的视网膜神经球的扩增群体表达了许多神经发育和眼特异性基因以及神经和视网膜祖细胞的特征性标记物，但逐渐失去了分化后产生神经元的潜力。Mash1的错误表达恢复了长期培养的神经原性潜能，产生具有多种视网膜内细胞类型的表型特征的神经元。因此，需要一种新的外在和内在因素的组合，以促进人视网膜神经球培养物中的祖细胞增殖和神经元多能性。这些结果支持RPE在人视网膜发育中的促增殖和抗凋亡作用，揭示了人视网膜祖细胞培养系统的潜在局限性，并提出了克服体外细胞命运限制的方法。
During development of the central nervous system, stem and progenitor cell proliferation and differentiation are controlled by complex inter- and intracellular interactions that orchestrate the precise spatiotemporal production of particular cell types. Within the embryonic retina, progenitor cells are located adjacent to the retinal pigment epithelium (RPE), which differentiates prior to the neurosensory retina and has the capacity to secrete a multitude of growth factors. We found that secreted proteinaceous factors in human prenatal RPE conditioned media (RPE CM) prolonged and enhanced the growth of human prenatal retinal neurospheres. The growth-promoting activity of RPE CM was mitogen-dependent and associated with an acute increase in transcription factor phosphorylation. Expanded populations of RPE CM-treated retinal neurospheres expressed numerous neurodevelopmental and eye specification genes and markers characteristic of neural and retinal progenitor cells, but gradually lost the potential to generate neurons upon differentiation. Misexpression of Mash1 restored the neurogenic potential of long term cultures, yielding neurons with phenotypic characteristics of multiple inner retinal cell types. Thus, a novel combination of extrinsic and intrinsic factors was required to promote both progenitor cell proliferation and neuronal multipotency in human retinal neurosphere cultures. These results support a pro-proliferative and anti-apoptotic role for RPE in human retinal development, reveal potential limitations of human retinal progenitor culture systems, and suggest a means for overcoming cell fate restriction in vitro.
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影响因子：
25
作者：
Fischer, AJ;Reh, TA
通讯作者：
Reh, TA
影响因子：
2.5
作者：
de Melo, J;Qiu, XG;Eisenstat, DD
通讯作者：
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影响因子：
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作者：
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影响因子：
3.1
作者：
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通讯作者：
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DOI：
10.1073/pnas.94.7.3088
发表时间：
1997-04-01
影响因子：
11.1
作者：
Furukawa, T;Kozak, CA;Cepko, CL
通讯作者：
Cepko, CL