RRC ID 44005
Author Salti A, Nat R, Neto S, Puschban Z, Wenning G, Dechant G.
Title Expression of early developmental markers predicts the efficiency of embryonic stem cell differentiation into midbrain dopaminergic neurons.
Journal Stem Cells Dev
Abstract Dopaminergic neurons derived from pluripotent stem cells are among the best investigated products of in vitro stem cell differentiation owing to their potential use for neurorestorative therapy of Parkinson's disease. However, the classical differentiation protocols for both mouse and human pluripotent stem cells generate a limited percentage of dopaminergic neurons and yield a considerable cellular heterogeneity comprising numerous scarcely characterized cell populations. To improve pluripotent stem cell differentiation protocols for midbrain dopaminergic neurons, we established extensive and strictly quantitative gene expression profiles, including markers for pluripotent cells, neural progenitors, non-neural cells, pan-neuronal and glial cells, neurotransmitter phenotypes, midbrain and nonmidbrain populations, floor plate and basal plate populations, as well as for Hedgehog, Fgf, and Wnt signaling pathways. The profiles were applied to discrete stages of in vitro differentiation of mouse embryonic stem cells toward the dopaminergic lineage and after transplantation into the striatum of 6-hydroxy-dopamine-lesioned rats. The comparison of gene expression in vitro with stages in the developing ventral midbrain between embryonic day 11.5 and 13.5 ex vivo revealed dynamic changes in the expression of transcription factors and signaling molecules. Based on these profiles, we propose quantitative gene expression milestones that predict the efficiency of dopaminergic differentiation achieved at the end point of the protocol, already at earlier stages of differentiation.
Volume 22(3)
Pages 397-411
Published 2013-2-1
DOI 10.1089/scd.2012.0238
PMID 22889265
PMC PMC3549628
MeSH Animals Antigens, Differentiation / genetics Antigens, Differentiation / metabolism Cell Differentiation* Cells, Cultured Dopaminergic Neurons / metabolism* Dopaminergic Neurons / physiology Dopaminergic Neurons / transplantation Embryonic Stem Cells / metabolism* Embryonic Stem Cells / physiology Gene Expression Genes, Developmental Intracellular Signaling Peptides and Proteins / genetics Intracellular Signaling Peptides and Proteins / metabolism Male Mesencephalon / metabolism* Mesencephalon / pathology Mice Mice, Inbred C57BL Mice, Transgenic Neural Stem Cells / metabolism* Neural Stem Cells / physiology Neural Stem Cells / transplantation Parkinson Disease, Secondary / pathology Parkinson Disease, Secondary / therapy Rats Rats, Wistar Signal Transduction Transcriptome
IF 3.153
Times Cited 12
Human and Animal Cells