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Lineage Tracing and Clonal Analysis in Developing Cerebral Cortex Using Mosaic Analysis with Double Markers MADM
Published on: May 8, 2020
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Single-cell transcriptome analysis reveals cell lineage specification in temporal-spatial patterns in human cortical
Xiaoying Fan1,2,3, Yuanyuan Fu4, Xin Zhou3,5
1Beijing Advanced Innovation Center for Genomics, Department of Obstetrics and Gynecology, College of Life Sciences, Third Hospital, Peking University, Beijing 100871, China.
Science Advances
|September 14, 2020
Summary
This study reveals distinct human neural progenitor cell subtypes and maps their development during early human brain growth. It decodes molecular regulations of neurogenesis and neuronal development across the cortex.
Area of Science:
- Developmental Neuroscience
- Genomics
- Human Embryology
Background:
- Neurogenesis, the process of generating new neurons, varies across cortical regions in humans.
- Understanding human neurodevelopment is crucial for insights into brain evolution and disorders.
Purpose of the Study:
- To profile the transcriptome of neural progenitor cells (NPCs) across human cortical lobes and pons during embryonic and fetal development.
- To identify novel NPC subtypes and elucidate the molecular mechanisms governing human neurogenesis and neuronal differentiation.
- To map the spatial and temporal dynamics of human cortical development from GW7 to GW28.
Main Methods:
- Single-cell RNA sequencing (scRNA-seq) of cortical and pons tissues from human embryonic and fetal stages (GW7-GW28).
- Bioinformatic analysis to identify cell subtypes, developmental trajectories, and molecular signatures.
- Validation of region-specific neuronal characteristics, including electrophysiological properties.
Main Results:
- Discovery of distinct neural progenitor cell (NPC) subtypes, including previously unidentified transient NPCs.
- Detailed mapping of neurogenesis pathways and molecular regulations for deep-layer, upper-layer, and mature human neurons.
- Identification of conserved developmental patterns in glial cells compared to mice and tracking of oligodendrocyte lineage development.
- Confirmation of region-specific neuronal properties and distinct electrophysiological features in cortical neurons.
Conclusions:
- Single-cell transcriptome profiling provides a comprehensive map of human neurogenesis and cortical development.
- The study elucidates the molecular underpinnings of neuronal diversity and spatial-temporal patterning in the developing human brain.
- Findings offer critical insights into the complex processes governing human brain formation and provide a foundation for future research.
