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Comparative single-cell multiome identifies evolutionary changes in neural progenitor cells during primate brain

Yuting Liu1, Xin Luo2, Yiming Sun3

  • 1State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China; School of Life Sciences, Center for Bioinformatics, Center for Statistical Science, Peking University, Beijing 100871, China.

Developmental Cell
|October 31, 2024
PubMed
Summary
This summary is machine-generated.

Human neural progenitors evolved unique traits, altering growth factor and extracellular matrix pathways. These changes, linked to human intelligence and brain disorders, reveal primate brain evolution mechanisms.

Keywords:
brain developmentbrain evolutionchromatin accessibilitygene regulationneural progenitorsprimate cortexregulatory elementssingle-cell multi-omicstranscriptome

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Area of Science:

  • Neuroscience
  • Developmental Biology
  • Evolutionary Biology

Background:

  • Understanding human-specific brain evolution requires detailed analysis of cortical development.
  • Cellular and genetic mechanisms underlying primate brain uniqueness are not fully elucidated.

Purpose of the Study:

  • To create a cell-type resolved atlas of transcriptome and chromatin accessibility in developing macaque and mouse prefrontal cortex (PFC).
  • To compare these data with human data to identify evolutionary divergences in cortical development.

Main Methods:

  • Generated cell-type resolved transcriptomic and chromatin accessibility atlases.
  • Compared macaque and mouse PFC data with published human data.
  • Investigated the function of the human-specific progenitor marker ITGA2 in fetal mouse cortex.

Main Results:

  • Cortical cellular composition is largely conserved, but progenitor cells show significant evolutionary divergence.
  • Human neural progenitors exhibit transcriptional rewiring in growth factor and extracellular matrix (ECM) pathways.
  • Human-gained chromatin accessibility regions contain sequence changes linked to intelligence and neuropsychiatric disorders.

Conclusions:

  • Evolutionary changes in neural progenitors are key to primate brain evolution.
  • Altered regulatory element activity drives transcriptional divergence in human progenitors.
  • Identified putative gene regulatory mechanisms shaping primate brain evolution.