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Efficient Differentiation of Human Embryonic Stem Cells into Functional Cerebellar-Like Cells

Authors: Erceg S.; Ronaghi M.; Zipančić I.; Laínez S.; Roselló M.; Xiong C.; Moreno-Manzano V.; +5 Authors

Efficient Differentiation of Human Embryonic Stem Cells into Functional Cerebellar-Like Cells

Abstract

The cerebellum has critical roles in motor and sensory learning and motor coordination. Many cerebellum-related disorders indicate cell therapy as a possible treatment of neural loss. Here we show that application of inductive signals involved in early patterning of the cerebellar region followed by application of different factors directs human embryonic stem cell differentiation into cerebellar-like cells such as granule neurons, Purkinje cells, interneuron, and glial cells. Neurons derived using our protocol showed a T-shaped polarity phenotype and express similar markers to the developed human cerebellum. Electrophysiological measurements confirmed functional electrical properties compatible with these cells. In vivo implantation of differentiated human embryonic stem cells transfected with MATH1-GFP construct into neonatal mice resulted in cell migration across the molecular and the Purkinje cell layers and settlement in the internal molecular layers. Our findings demonstrate that the universal mechanisms involved in the development of cerebellum can be efficiently recapitulated in vitro, which enables the design of new strategies for cell replacement therapy, to study early human development and pathogenesis of neurodegenerative diseases.

Country
Serbia
Keywords

Adult, Basic Helix-Loop-Helix Proteins, Male, Embryonic stem cells, Patch-Clamp Techniques, ATOH1 protein, Action Potentials, Gestational Age, Mice, Fetus, Pregnancy, Cell Movement, Cerebellum, Basic Helix-Loop-Helix Transcription Factors, Animals, Humans, Cells, Cultured, Embryonic Stem Cells, Aged, Neurons, Biological markers, Stem cell transplantation, Cell Differentiation, Middle Aged, Recombinant fusion proteins, Embryonic stem cells (ESCs), Female, Biomarkers

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selected citations
These citations are derived from selected sources.
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
views
OpenAIRE UsageCountsViews provided by UsageCounts
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53
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