REVIEW
Specification of neuronal and glial subtypes from human
pluripotent stem cells
Huisheng Liu
•
Su-Chun Zhang
Received: 26 April 2011 / Revised: 29 June 2011 / Accepted: 5 July 2011 / Published online: 24 July 2011
Ó Springer Basel AG 2011
Abstract Human pluripotent stem cells (PSCs), including
embryonic stem cells (ESCs) and induced pluripotent stem
cells (iPSCs), provide a dynamic tool for revealing early
embryonic development, modeling pathological processes,
and developing therapeutics through drug discovery and
potential cell replacement. The first step toward the utilities
of human PSCs is directed differentiation to functionally
specialized cell/tissue types. Following developmental
principles, human ESCs, and lately iPSCs, have been
effectively differentiated to region- and/or transmitter-
specific neuronal and glial types, including cerebral
glutamatergic, striatal c-aminobutyric acid (GABA)-ergic,
forebrain cholinergic, midbrain dopaminergic, and spinal
motor neurons, as well as astrocytes and oligodendrocytes.
These studies also reveal unique aspects of human cell
biology, including intrinsically programmed developmen-
tal course, differential uses of transcription factors for
neuroectoderm specification, and distinct responses to
extracellular signals in regulating cell fate. Such informa-
tion will be instrumental in translating biological findings
to therapeutic development.
Keywords Embryonic stem cells Á
Induced pluripotent stem cells Á Neural stem cells Á
Patterning Á Transcriptional regulation Á Transplantation Á
Drug screening
Introduction
Human PSCs, including those derived from preimplanta-
tion embryos, known as ESCs, and those reprogrammed
from somatic cells, called iPSCs, have the potential
to differentiate to hundreds of cell types of the three
embryonic germ layers while maintaining the ability of
self-renew [1–4]. Differentiation of human PSCs into
specialized cell types in vitro as well as in vivo (e.g., ter-
atoma formation) is essentially recapitulation of embryonic
development. Hence, human PSCs are potentially instru-
mental in revealing early human development, which is
otherwise experimentally inaccessible. In this regard,
iPSCs derived from patients with developmental disorders
may provide a platform to identify missteps in early stages
that lead to abnormal development. Like mouse ESCs,
human ESCs may be genetically altered to express disease
phenotypes, thus offering a dynamic model system for
following pathogenic processes. Similarly, iPSCs repro-
grammed from patients’ somatic cells, especially those
with genetic defects, can potentially achieve the same goal
while at the naturally occurring human genetic background.
Both genetically modified human ESCs and disease iPSCs
may be used for drug discovery. Recently, functional
neurons, the so-called iN cells, are induced directly from
fibroblasts by overexpression of neuronal transcription
factors, such as Ascl1, Brn2, and Mytl [5, 6]. Such a pro-
cess bypasses stem cell and progenitor stages, thus
generating mature neurons in a much shorter time, which
H. Liu Á S.-C. Zhang (&)
Waisman Center, University of Wisconsin,
1500 Highland Avenue, Madison, WI 53705, USA
e-mail: zhang@waisman.wisc.edu
S.-C. Zhang
Department of Neuroscience and Department of Neurology,
School of Medicine and Public Health, University of Wisconsin,
Madison, WI, USA
Cell. Mol. Life Sci. (2011) 68:3995–4008
DOI 10.1007/s00018-011-0770-y
Cellular and Molecular Life Sciences
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