Single-Cell Analysis of Foxp1-Driven Mechanisms Essential for Striatal Development.

Cell Reports
Ashley G AndersonGenevieve Konopka

Abstract

The striatum is a critical forebrain structure integrating cognitive, sensory, and motor information from diverse brain regions into meaningful behavioral output. However, the transcriptional mechanisms underlying striatal development at single-cell resolution remain unknown. Using single-cell RNA sequencing (RNA-seq), we examine the cellular diversity of the early postnatal striatum and show that Foxp1, a transcription factor strongly linked to autism and intellectual disability, regulates the cellular composition, neurochemical architecture, and connectivity of the striatum in a cell-type-dependent fashion. We also identify Foxp1-regulated target genes within distinct cell types and connect these molecular changes to functional and behavioral deficits relevant to phenotypes described in patients with FOXP1 loss-of-function mutations. Using this approach, we could also examine the non-cell-autonomous effects produced by disrupting one cell type and the molecular compensation that occurs in other populations. These data reveal the cell-type-specific transcriptional mechanisms regulated by Foxp1 that underlie distinct features of striatal circuitry.

Citations

Jan 28, 2021·RNA Biology·Aida Cardona-AlberichChristopher R Sibley
Aug 7, 2021·Frontiers in Human Neuroscience·Tim Fieblinger
Sep 9, 2020·Neurobiology of Disease·Margaux LeboucJérôme Baufreton

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Datasets Mentioned

BETA
AB10518
GSE125290

Methods Mentioned

BETA
scRNA-Seq
RNA-seq
single-cell sequencing

Software Mentioned

bcl2fastq
Subread package
ImageJ
FASTQC
NiftyReg
BioHPC
UCSC genome browser
Photobeam Activity System - Home Cage
Associates
Ilastik ( Interactive learning and segmentation toolkit

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