Related Experiment Video
Updated: May 10, 2026
10:25
Generation of Standardized and Reproducible Forebrain-type Cerebral Organoids from Human Induced Pluripotent Stem Cells
Published on: January 23, 2018
21.4K
Cerebral organoids display dynamic clonal growth and tunable tissue replenishment
Dominik Lindenhofer1,2,3, Simon Haendeler2,4, Christopher Esk5,6
1Institute of Molecular Biotechnology of the Austrian Academy of Science, Vienna BioCenter, Vienna, Austria.
Nature Cell Biology
|May 7, 2024
Summary
Neural stem cell clones in human brain organoids vary greatly in size due to asymmetric and symmetric divisions. This variability ensures robust brain development even after perturbations.
Area of Science:
- Developmental biology
- Neuroscience
- Stem cell biology
Background:
- Neural progenitors divide symmetrically to expand and asymmetrically to differentiate.
- Variability in division modes leads to diverse stem cell clone sizes.
- Existing lineage tracing methods lack systematic whole-tissue analysis.
Purpose of the Study:
- To investigate clonal behavior and variability in human cerebral organoids.
- To understand the mechanisms generating variable stem cell clone sizes.
- To explore the adaptive plasticity of neural stem cell populations.
Main Methods:
- Whole-tissue lineage tracing using genomic DNA barcoding in 3D human cerebral organoids.
- Stochastic modeling to analyze lineage size variations.
- Perturbation experiments using chemical ablation and genetic restriction in chimeric organoids.
Main Results:
- Individual stem cell clones exhibit vastly variable progeny scales.
- Variable lineage sizes result from a subpopulation of lineages maintaining symmetric divisions.
- Stem cell populations demonstrate adaptive plasticity, adjusting lineage sizes in response to growth perturbations.
Conclusions:
- Symmetric cell divisions in a subset of lineages drive variable clone sizes during brain development.
- Adaptive plasticity in neural stem cell populations ensures developmental robustness in human brain organoids.
- Genomic DNA barcoding in organoids provides a powerful tool for whole-tissue lineage analysis.
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