期刊
GENE
卷 534, 期 2, 页码 400-407出版社
ELSEVIER
DOI: 10.1016/j.gene.2013.07.101
关键词
Induced pluripotent stem cells; Neural rosettes; Radial glia; Mature pyramidal neurons
资金
- Ann & Robert H Lurie Children's Hospital of Chicago Research Center Excellence in Academic Medicine Grant from the Illinois Department of Public Aid
- Dr. Ralph and Marian C. Falk Medical Research Trust
- Children Research Fund
- Gus Foundation
- Maeve McNicholas Memorial Foundation
- Everett/O'Connor Charitable Trust
- NIH/NCI [CA121205]
- Medical Research Institute Council
- Northwestern University Flow Cytometry Facility a Cancer Center Support Grant [NCI CA060553]
- NIH ARRA Grant [RC1HL100168]
In vitro neural differentiation of human embryonic stem cells (hESCs) is an advantageous system for studying early neural development. The process of early neural differentiation in hESCs begins by initiation of primitive neuroectoderm, which is manifested by rosette formation, with consecutive differentiation into neural progenitors and early glial-like cells. In this study, we examined the involvement of early neural markers - OTX2, PAX6, Sox1, Nestin, NR2F1, NR2F2, and IRX2 - in the onset of rosette formation, during spontaneous neural differentiation of hESC and human induced pluripotent stem cell (hiPSC) colonies. This is in contrast to the conventional way of studying rosette formation, which involves induction of neuronal differentiation and the utilization of emblyoid bodies. Here we show that OTX2 is highly expressed at the onset of rosette formation, when rosettes comprise no more than 3-5 cells, and that its expression precedes that of established markers of early neuronal differentiation. Importantly, the rise of OTX2 expression in these cells coincides with the down-regulation of the pluripotency marker OCT4. Lastly, we show that cells derived from rosettes that emerge during spontaneous differentiation of hESCs or hiPSCs are capable of differentiating into dopaminergic neurons in vitro, and into mature-appearing pyramidal and serotonergic neurons weeks after being injected into the motor cortex of NOD-SOD mice. (C) 2013 Elsevier B.V. All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据