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Related Concept Videos

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Related Experiment Video

Updated: Jan 12, 2026

Lineage Tracing and Clonal Analysis in Developing Cerebral Cortex Using Mosaic Analysis with Double Markers MADM
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Lineage-resolved atlas of the developing human cortex.

Matthew G Keefe1,2,3,4,5,6, Marilyn R Steyert1,2,3,4,5,6, Tomasz J Nowakowski7,8,9,10,11,12

  • 1Department of Neurological Surgery, University of California San Francisco, San Francisco, CA, USA.

Nature
|November 5, 2025
PubMed
Summary
This summary is machine-generated.

Researchers mapped human neocortex development by tracing 6,402 neural progenitor cells. This revealed progenitor cell fate switching and the origin of deep cortical layer neurons, advancing our understanding of human brain development.

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Area of Science:

  • Neuroscience
  • Developmental Biology
  • Genetics

Background:

  • The human neocortex contains diverse cell types generated during development.
  • Understanding lineage relationships in human cortical development is crucial but remains largely unknown.
  • Previous studies captured gene expression snapshots but lacked lineage resolution.

Purpose of the Study:

  • To map the differentiation pathways of human neural stem and progenitor cells.
  • To create a lineage-resolved map of human cortical development.
  • To identify the origins of specific neuron and glia subtypes.

Main Methods:

  • Prospective lineage tracing of 6,402 progenitor cells in human primary tissue.
  • Profiling clonal output to understand cell differentiation.
  • Analyzing gene expression to resolve lineage relationships.

Main Results:

  • Cortical progenitors switch from glutamatergic to GABAergic neurogenesis around midgestation.
  • Oligodendrocyte generation begins around midgestation.
  • Truncated radial glia generate deep cortical layer neurons late in development.
  • These late-born neurons may contribute to subplate expansion.

Conclusions:

  • A lineage-resolved map of human cortical development was established.
  • The study reveals dynamic changes in progenitor cell fate during human brain development.
  • New insights into the generation of deep cortical layers and subplate neurons were uncovered.