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Rapid Neuronal Differentiation of Induced Pluripotent Stem Cells for Measuring Network Activity on Micro-electrode Arrays

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Widespread Translational Remodeling during Human Neuronal Differentiation.

John D Blair¹, Dirk Hockemeyer¹, Jennifer A Doudna²

¹Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA.

|November 16, 2017

Summary

Human stem cell differentiation into neurons involves significant changes in gene translation, not just RNA levels. Regulatory sequences in 3' untranslated regions (UTRs) control translation in mature neurons.

Keywords:

RNA TrIP-seq cellular differentiation human stem cell neural progenitor cell neurogenesis neuron polysome profiling ribosome profiling translational control

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Post-differentiation Replating of Human Pluripotent Stem Cell-derived Neurons for High-content Screening of Neuritogenesis and Synapse Maturation

Post-differentiation Replating of Human Pluripotent Stem Cell-derived Neurons for High-content Screening of Neuritogenesis and Synapse Maturation

Published on: August 28, 2019

Area of Science:

Molecular Biology
Developmental Biology
Neuroscience

Background:

Cellular differentiation requires precise gene expression control at both transcriptional and translational levels.
Neuronal development involves complex mRNA regulation, but translational control mechanisms are not fully understood.
Human embryonic stem cells (hESCs) provide a model for studying human neuronal differentiation.

Purpose of the Study:

To investigate genome-wide translational changes during human forebrain neuronal differentiation.
To identify key regulators of translational control during this process.
To understand the role of 3' untranslated regions (UTRs) in cell-type-specific translation.

Main Methods:

Induced forebrain neuronal differentiation of hESCs.
Genome-wide measurement of RNA and translation levels with transcript-isoform resolution.
Analysis of mTOR signaling pathways and 3' UTR regulatory elements.

Main Results:

Thousands of genes exhibited altered translation without corresponding changes in RNA levels.
mTOR signaling was identified as a driver of elevated translation in hESCs.
Translational repression in active neurons is mediated by 3' UTR sequences.

Conclusions:

Extensive translational control changes occur during human neuronal differentiation.
3' UTRs play a crucial role in establishing cell-type-specific translation patterns in neurons.
This study reveals novel insights into post-transcriptional regulation during human development.