Open AccessDirected Neural Differentiation of Human Embryonic Stem Cells via an Obligated Primitive Anterior Stage
Author(s) -
Pankratz Matthew T.,
Li XueJun,
LaVaute Timothy M.,
Lyons Elizabeth A.,
Chen Xin,
Zhang SuChun
Publication year - 2007
Publication title -
stem cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.159
H-Index - 229
eISSN - 1549-4918
pISSN - 1066-5099
DOI - 10.1634/stemcells.2006-0707
Subject(s) - neuroectoderm , biology , neural plate , embryonic stem cell , neural tube , neural stem cell , neural development , microbiology and biotechnology , stem cell , neuroscience , anatomy , genetics , mesoderm , embryo , gene
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. Disclosure of potential conflicts of interest is found at the end of this article.