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Homochronic Transplantation of Interneuron Precursors into Early Postnatal Mouse Brains
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Mouse and human share conserved transcriptional programs for interneuron development.

Yingchao Shi1, Mengdi Wang1,2, Da Mi3,4,5

  • 1State Key Laboratory of Brain and Cognitive Science, CAS Center for Excellence in Brain Science and Intelligence Technology (Shanghai), Institute of Biophysics, Chinese Academy of Sciences (CAS), BNU IDG/McGovern Institute for Brain Research, Beijing 100101, China.

Science (New York, N.Y.)
|December 9, 2021
PubMed
Summary
This summary is machine-generated.

Genetic variations impact neurodevelopmental disorders by altering specific brain cells. This study reveals conserved mechanisms in human fetal brain development for generating key inhibitory neurons, crucial for conditions like autism and schizophrenia.

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Area of Science:

  • Neuroscience
  • Developmental Biology
  • Genetics

Background:

  • Neurodevelopmental disorders, including autism and schizophrenia, are linked to alterations in specific neuronal populations.
  • Cortical and striatal gamma-aminobutyric acid–expressing (GABAergic) neurons are particularly implicated in these conditions.
  • Understanding the early development of these neurons is critical for deciphering disease mechanisms.

Purpose of the Study:

  • To characterize the cellular diversity and developmental trajectories of GABAergic neurons in the human fetal brain.
  • To investigate the transcriptional programs governing the specification and differentiation of these neurons.
  • To compare human GABAergic neuron development with established rodent models.

Main Methods:

  • Single-cell RNA sequencing (scRNA-seq) was employed to analyze cell populations in human ganglionic eminences.
  • scRNA-seq data was used to identify regional and temporal diversity among progenitor cells.
  • Computational analysis was performed to infer transcriptional regulatory logic.

Main Results:

  • Identified significant regional and temporal diversity within progenitor cells of the human ganglionic eminences.
  • Characterized the emergence of diverse projection neurons and interneurons.
  • Found that transcriptional programs for GABAergic neuron specification in humans are similar to those in rodents.
  • Revealed conserved regulatory mechanisms controlling GABAergic neuron development in the human telencephalon.

Conclusions:

  • The human ganglionic eminences exhibit complex progenitor cell diversity crucial for generating various GABAergic neuron types.
  • The developmental pathways for human GABAergic neurons share conserved regulatory logic with rodents.
  • These findings provide insights into the evolutionary basis of human brain development and neurodevelopmental disorders.