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GENERATION OF MOUSE NEOCORTICAL ORGANOIDS TO MODEL THE IMPACT OF CIS-REGULATORY VARIATION ON CORTICAL NEUROGENESIS ACROSS EVOLUTIONARY TIMESCALES (scRNA-Seq)

ABSTRACT: GENERATION OF MOUSE NEOCORTICAL ORGANOIDS TO MODEL THE IMPACT OF CIS-REGULATORY VARIATION ON CORTICAL NEUROGENESIS ACROSS EVOLUTIONARY TIMESCALES (scRNA-Seq)

PROVIDER: PRJNA1116224 | ENA |

REPOSITORIES: ENA

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GENERATION OF MOUSE NEOCORTICAL ORGANOIDS TO MODEL THE IMPACT OF CIS-REGULATORY VARIATION ON CORTICAL NEUROGENESIS ACROSS EVOLUTIONARY TIMESCALES (scRNA-Seq)

Project description:Natural selection has shaped the gene regulatory networks that orchestrate the development of the neocortex, leading to diverse neocortical structure and function across mammals, but the molecular and cellular mechanisms driving phenotypic changes have proven difficult to characterize. Here, we develop a reproducible protocol to generate cortical organoids from mouse epiblast stem cells that enable in depth mechanistic studies of cortical developmental in vitro. Cortical organoids develop with similar kinetics to the mouse cortex in vivo, recapitulate the cellular diversity present in the embryonic neocortex, and undergo relatively rapid maturation compared to human organoids. We generated cortical organoids from F1 hybrid epiblast stem cell lines from crosses between standard laboratory mice (C57Bl/6J) and four wild-derived inbred mouse strains from distinct sub-species that span ~1 million years of evolutionary divergence. Using scRNA-seq and allele-specific expression analysis we identified hundreds of genes that exhibit differential cis-regulation during cortical neurogenesis. These experimental methods and cellular resources represent a powerful new platform for investigating gene regulatory mechanisms across evolutionary timescales.

2024-10-20 | GSE268332 | GEO

GENERATION OF MOUSE NEOCORTICAL ORGANOIDS TO MODEL THE IMPACT OF CIS-REGULATORY VARIATION ON CORTICAL NEUROGENESIS ACROSS EVOLUTIONARY TIMESCALES (scATAC-Seq)

2024-10-20 | GSE268331 | GEO

GENERATION OF MOUSE NEOCORTICAL ORGANOIDS TO MODEL THE IMPACT OF CIS-REGULATORY VARIATION ON CORTICAL NEUROGENESIS ACROSS EVOLUTIONARY TIMESCALES (bulk RNA-Seq)

2024-10-20 | GSE268329 | GEO

GENERATION OF MOUSE NEOCORTICAL ORGANOIDS TO MODEL THE IMPACT OF CIS-REGULATORY VARIATION ON CORTICAL NEUROGENESIS ACROSS EVOLUTIONARY TIMESCALES

Project description:GENERATION OF MOUSE NEOCORTICAL ORGANOIDS TO MODEL THE IMPACT OF CIS-REGULATORY VARIATION ON CORTICAL NEUROGENESIS ACROSS EVOLUTIONARY TIMESCALES

| PRJNA1116220 | ENA

GENERATION OF MOUSE NEOCORTICAL ORGANOIDS TO MODEL THE IMPACT OF CIS-REGULATORY VARIATION ON CORTICAL NEUROGENESIS ACROSS EVOLUTIONARY TIMESCALES (scATAC-Seq)

Project description:GENERATION OF MOUSE NEOCORTICAL ORGANOIDS TO MODEL THE IMPACT OF CIS-REGULATORY VARIATION ON CORTICAL NEUROGENESIS ACROSS EVOLUTIONARY TIMESCALES (scATAC-Seq)

| PRJNA1116225 | ENA

GENERATION OF MOUSE NEOCORTICAL ORGANOIDS TO MODEL THE IMPACT OF CIS-REGULATORY VARIATION ON CORTICAL NEUROGENESIS ACROSS EVOLUTIONARY TIMESCALES (bulk RNA-Seq)

Project description:GENERATION OF MOUSE NEOCORTICAL ORGANOIDS TO MODEL THE IMPACT OF CIS-REGULATORY VARIATION ON CORTICAL NEUROGENESIS ACROSS EVOLUTIONARY TIMESCALES (bulk RNA-Seq)

| PRJNA1116227 | ENA

GENERATION OF MOUSE NEOCORTICAL ORGANOIDS TO MODEL THE IMPACT OF CIS-REGULATORY VARIATION ON CORTICAL NEUROGENESIS ACROSS EVOLUTIONARY TIMESCALES

Project description:This SuperSeries is composed of the SubSeries listed below.

2024-10-20 | GSE268333 | GEO

Meningeal-derived retinoic acid regulates neurogenesis via suppression of Notch and Sox2 [Spatial Transcriptomics]

Project description:During development, the meninges act as a regulator of neocortical development by secreting ligands that act on neural cells to regulate neurogenesis and neuronal migration. Meninges-derived retinoic acid (RA) promotes neocortical progenitor cell cycle exit however the underlying mechanism is unknown. Here, we use Foxc1-mutant embryos that lack meninges-derived ligands, spatial transcriptomics, and profiling of retinoic-acid receptor-a (RARa) DNA binding to identify the neurogenic transcriptional mechanisms of RA signaling in cortical neural progenitors. We determined that meningeal-derived RA controls neurogenesis by suppressing self-renewal pathways Notch signaling and the transcription factor Sox2. We show that RARα binds in the Sox2ot promoter, a long non-coding RNA that regulates Sox2 expression, and RA promotes Sox2ot expression in neocortical progenitors. Our findings elucidate a previously unknown mechanism of howmeningeal RA coordinates neocortical development and insight into how defects in meningeal develop can cause neurodevelopmental disorders.

2024-09-25 | GSE269283 | GEO

Meningeal-derived retinoic acid regulates neurogenesis via suppression of Notch and Sox2 [CUT&Run]

2024-09-25 | GSE269282 | GEO

Meningeal cells contribute to postnatal cortical neurogenesis.

Project description:Postnatal brain neurogenesis in mammals is believed to be restricted to rare germinative remnants of the neuroepithelium. In this study, we discovered that, in the postnatal brain, a subset of embryonically derived progenitors is present in meningeal substructures. These cells migrate from the meningeal substructures to the retrosplenial and visual motor cortex and differentiate into (electrically) functional integrated neurons. Lineage tracing analysis revealed that this subset of neural progenitors originate largely from PDGFR+ cells. PDGFR-derived cells differentiate mostly into Satb2+ neurons in cortical layers I-IV. Thus, a reservoir of embryonically derived progenitors in the meninges contributes to postnatal cerebral cortical neurogenesis.

2016-11-23 | E-MTAB-4951 | biostudies-arrayexpress

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