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Directing Differentiation of Embryonic Stem Cells into Distinct Neuronal Subtypes

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Perspectives of Stem Cells

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Abstract

There is great interest in testing the efficacy of treating neurodegenerative diseases using embryonic stem cell derivatives. A first step towards this goal is demonstrating that embryonic stem cells can produce, in culture, the specific cell types lost in the various diseases. We describe here currently used approaches for generating neural stem cells, as well as specific neuronal subtypes, from mouse and human embryonic stem cells. Based upon their demonstrated role in neurodegenerative disease and the reports documenting their derivation from embryonic stem cells, we focus on dopaminergic neurons, GABAergic interneurons, spinal cord motor neurons, serotonergic neurons, and basal forebrain cholinergic neurons. Protocols are all based upon what has been learned about the conditions that promote emergence of these lineages in the embryo.

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Abbreviations

5-HT:

5-hydroxytryptamine (serotonin)

AA:

ascorbic acid

AADC:

amino acid decarboxylase

ACh:

acetylcholine

AD:

Alzheimer’s disease

ALS:

Amyotrophic Lateral Sclerosis

BAC:

bacterial artificial chromosome

BDNF:

brain derived neurotrophic factor

BMP:

bone morphogenic protein

cAMP:

cyclic adenosine monophosphate

CB:

calbindin

CCK:

cholecystokinin

CGE:

caudal ganglionic eminences

CNS:

central nervous system

CR:

calretinin

DA:

dopaminergic

DV:

dorsal-ventral

EGF:

epidermal growth factor

EPL:

primitive ectoderm-like

ESC:

embryonic stem cell(s)

FACS:

fluorescence activated cell sorting

FGF:

fibroblast growth factor

GABA:

γ-aminobutyric acid

GAD:

glutamic acid decarboxylase

GDNF:

glial cell derived neurotrophic factor

Glu:

glutamate

hESC:

human embryonic stem cell(s)

Hh:

hedgehog

iPS:

induced pluripotent stem cell

MAP2:

microtubule associated protein 2

mDA:

midbrain dopaminergic

mES cells:

mouse embryonic stem cells

MGE:

medial ganglionic eminences

MN:

motor neuron(s)

MPTP:

1-methyl-4-phenyl-1,2,3,6-tetrahycopyridine

NGF:

nerve growth factor

NPY:

neuropeptide Y

NSC:

neural stem cell(s)

NT-4:

neurotrophin 4

PD:

Parkinson’s disease

PDD:

Parkinsonian disease dementia

pMN:

motor neuron progenitor(s)

PV:

parvalbumin

RA:

retinoic acid

SCI:

spinal cord injuries

Shh:

sonic hedgehog

SMA:

Spinal Muscular Atrophy

SNi:

substantia nigra

SSRI:

serotonin selective reuptake inhibitors

SST:

somatostatin

TGF-β:

transforming growth factor β

TH:

tyrosine hydroxylase

TLE:

temporal lobe epilepsy

VIP:

vasoactive intestinal peptide

VMAT2:

vesicular monoamine transporter 2

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  1. Hall-Atwater Laboratories, Biology Department, Wesleyan University, Middletown, CT, USA

    Noelle Ammon, Nathaniel Hartman & Laura Grabel

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  1. Noelle Ammon
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  2. Nathaniel Hartman
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Correspondence to Laura Grabel .

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  1. Inst. Química, Universidade de São Paulo, Av. Prof. Lineu Prestes 748, São Paulo, 05508-900, Brazil

    Henning Ulrich

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Ammon, N., Hartman, N., Grabel, L. (2010). Directing Differentiation of Embryonic Stem Cells into Distinct Neuronal Subtypes. In: Ulrich, H. (eds) Perspectives of Stem Cells. Springer, Dordrecht. https://doi.org/10.1007/978-90-481-3375-8_8

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