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Related Experiment Video

Updated: Oct 2, 2025

Lineage Tracing and Clonal Analysis in Developing Cerebral Cortex Using Mosaic Analysis with Double Markers MADM
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Clonal relations in the mouse brain revealed by single-cell and spatial transcriptomics.

Michael Ratz1, Leonie von Berlin1, Ludvig Larsson2

  • 1Department of Cell and Molecular Biology, Karolinska Institute, Stockholm, Sweden.

Nature Neuroscience
|February 25, 2022
PubMed
Summary
This summary is machine-generated.

This study uses in vivo barcoding to map cell development in the mouse brain. Researchers identified progenitor cells and traced the origins of microglia, revealing their developmental pathways and migration patterns.

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Area of Science:

  • Neuroscience
  • Developmental Biology
  • Genomics

Background:

  • The mammalian brain has diverse specialized cells originating from neuroepithelial progenitor cells.
  • Understanding lineage relationships between progenitor and mature brain cells remains a challenge.
  • Single-cell transcriptomics has identified numerous cell types but not their developmental origins.

Purpose of the Study:

  • To investigate lineage relationships between progenitor cells and mature cell types in the mouse brain.
  • To simultaneously profile cell phenotypes and clonal relationships using in vivo barcoding.
  • To reconstruct cell development and migration patterns at single-cell and tissue levels.

Main Methods:

  • In vivo barcoding of early neural progenitors in the mouse brain.
  • Application of single-cell and spatial transcriptomics.
  • Reconstruction of thousands of cell clones to infer lineage and migration.

Main Results:

  • Discovery of fate-restricted progenitor cells in the mouse hippocampal neuroepithelium.
  • Identification of microglia originating from a small number of primitive myeloid precursors with massive expansion.
  • Disentanglement of migration patterns for clonally related cells using combined spatial transcriptomics and clonal barcoding.

Conclusions:

  • The developed approach enables high-throughput reconstruction of cell phenotypes and clonal relations.
  • Provides an integrated method for understanding complex tissue architecture and cell development.
  • Offers new insights into the developmental origins and diversification of brain cell types, including microglia.