Related Experiment Video
Updated: Jul 8, 2025
10:47
Efficient Derivation of Human Neuronal Progenitors and Neurons from Pluripotent Human Embryonic Stem Cells with Small Molecule Induction
Published on: October 28, 2011
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Essential transcription factors for induced neuron differentiation
Congyi Lu1,2, Görkem Garipler2, Chao Dai1,2
1New York Genome Center, New York, NY, USA.
Nature Communications
|December 15, 2023
Summary
Neurogenins drive neuronal differentiation, but key regulators remain unknown. This study identifies essential transcription factors, like ZBTB18, crucial for neuron development and function.
Area of Science:
- Neuroscience
- Developmental Biology
- Genetics
Background:
- Neurogenins (NEUROG1, NEUROG2) are critical proneural transcription factors for specifying neuronal identity.
- Human pluripotent stem cells overexpressing neurogenins rapidly generate cortical-like neurons, valuable for disease modeling.
- Key downstream regulatory effectors driving neurogenesis remain incompletely understood.
Purpose of the Study:
- To identify essential transcription factors (TFs) that mediate directed neuronal differentiation.
- To develop an integrative platform for characterizing TFs involved in human cell differentiation.
Main Methods:
- Utilized inducible expression of NEUROG1 and NEUROG2 in human pluripotent stem cells.
- Combined expression and chromatin accessibility analyses with a pooled in vitro CRISPR-Cas9 screen targeting all human TFs.
- Investigated the functional impact of TF loss-of-function on neuronal differentiation and morphology.
Main Results:
- Identified several TFs essential for directed neuronal differentiation.
- Demonstrated that loss of ZBTB18 significantly impairs MAP2-positive neuron generation.
- Observed widespread gene expression alterations, cytoskeletal defects, and stunted neurites/spines in ZBTB18-null cells.
Conclusions:
- ZBTB18 is a crucial downstream TF for neuronal differentiation, impacting cell morphology and gene expression.
- The developed multi-omics and TFome-wide perturbation platform enables rapid characterization of essential TFs for any human cell type differentiation.
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