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EMBRYONIC STEM CELLS: CHARACTERIZATION SERIES |
aNeuroscience Training Program, University of Wisconsin-Madison, Madison, Wisconsin, USA;
bThe Stem Cell Research Program, Waisman Center, and the WiCell Institute, Madison, Wisconsin, USA;
cDepartments of Anatomy and Neurology, School of Medicine, University of Wisconsin-Madison, Madison, Wisconsin, USA;
dDepartment of Pathology, Stanford University Medical Center, Stanford, California, USA
Key Words. Neural differentiation • Neural stem cells • Pax6 • Neural induction
Correspondence: Su-Chun Zhang, M.D., Ph.D., Waisman Center, Rm T613, University of Wisconsin, 1500 Highland Ave., Madison, Wisconsin 53705, USA. Telephone: 608-265-2543; Fax: 608-263-5267; e-mail: zhang{at}waisman.wisc.edu
Received November 2, 2006;
accepted for publication February 20, 2007.
Disclosure of potential conflicts of interest is found at the end of this article.
First published online in STEM CELLS EXPRESS March 1, 2007.
Understanding neuroectoderm formation and subsequent diversification to functional neural subtypes remains elusive. We show here that human embryonic stem cells (hESCs) differentiate to primitive neuroectoderm after 8–10 days. At this stage, cells uniformly exhibit columnar morphology and express neural markers, including anterior but not posterior homeodomain proteins. The anterior identity of these cells develops regardless of morphogens present during initial neuroectoderm specification. This anterior phenotype can be maintained or transformed to a caudal fate with specific morphogens over the next week, when cells become definitive neuroepithelia, marked by neural tube-like structures with distinct adhesion molecule expression, Sox1 expression, and a resistance to additional patterning signals. Thus, primitive neuroepithelia represents the earliest neural cells that possess the potential to differentiate to regionally specific neural progenitors. This finding offers insights into early human brain development and lays a foundation for generating neural cells with correct positional and transmitter profiles.
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