Common regulatory targets of NFIA, NFIX and NFIB during postnatal cerebellar development
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ABSTRACT:
PROVIDER: PRJNA611985 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR11289900.fastq.gz | Fastqsanger.gz | |||
| SRR11289901.fastq.gz | Fastqsanger.gz | |||
| SRR11289902.fastq.gz | Fastqsanger.gz | |||
| SRR11289903.fastq.gz | Fastqsanger.gz | |||
| SRR11289904.fastq.gz | Fastqsanger.gz |
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Project description:Transcriptional regulation plays a central role in controlling neural stem and progenitor cell proliferation and differentiation during neurogenesis. For instance, transcription factors from the nuclear factor I (NFI) family have been shown to co-ordinate neural stem and progenitor cell differentiation within multiple regions of the embryonic nervous system, including the neocortex, hippocampus, spinal cord and cerebellum. Knockout of individual Nfi genes culminates in similar phenotypes, suggestive of common target genes for these transcription factors. However, whether or not the NFI family regulates common suites of genes remains poorly defined. Here, we use granule neuron precursors (GNPs) of the postnatal murine cerebellum as a model system to analyse regulatory targets of three members of the NFI family: NFIA, NFIB and NFIX. By integrating transcriptomic profiling (RNA-seq) of Nfia- and Nfix-deficient GNPs with epigenomic profiling (ChIP-seq against NFIA, NFIB and NFIX, and DNase I hypersensitivity assays), we reveal that these transcription factors share a large set of potential transcriptional targets, suggestive of complementary roles for these NFI family members in promoting neural development.
2020-03-12 | GSE146793 | GEO
Project description:Transcriptional regulation plays a central role in controlling neural stem and progenitor cell proliferation and differentiation during neurogenesis. For instance, transcription factors from the nuclear factor I (NFI) family have been shown to co-ordinate neural stem and progenitor cell differentiation within multiple regions of the embryonic nervous system, including the neocortex, hippocampus, spinal cord and cerebellum. Knockout of individual Nfi genes culminates in similar phenotypes, suggestive of common target genes for these transcription factors. However, whether or not the NFI family regulates common suites of genes remains poorly defined. Here, we use granule neuron precursors (GNPs) of the postnatal murine cerebellum as a model system to analyse regulatory targets of three members of the NFI family: NFIA, NFIB and NFIX. By integrating transcriptomic profiling (RNA-seq) of Nfia- and Nfix-deficient GNPs with epigenomic profiling (ChIP-seq against NFIA, NFIB and NFIX, and DNase I hypersensitivity assays), we reveal that these transcription factors share a large set of potential transcriptional targets, suggestive of complementary roles for these NFI family members in promoting neural development.
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Project description:Transcriptomes of E16 neocortical tissue knockout from Nfia, Nfib and Nfix knockout mice
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Project description:The goal of this study is to profile NFIA DNA-binding properties in the adult mouse brain. We performed chromatin immunoprecipitation of NFIA in the hippocampus and olfactory bulb of wildtype mice, and samples were subjected to sequencing. We find that NFIA preferentially binds DNA in the hippocampus but not in the olfactory bulb as evidenced by the distinct lack of NFIA binding peaks in the olfactory bulb. Mass spectrometry results suggested that NFIA has a significantly higher binding affinity for NFIB in the olfactory bulb, potentially blocking NFIA’s ability to bind DNA. Virally induced siRNAs against NFIB or scramble were injected into the olfactory bulb of adult wildtype mice to knock down NFIB. We performed chromatin immunoprecipitation of NFIA in the olfactory bulb injected with siRNA-NFIB or siRNA-scramble. Subsequent sequencing revealed an increase of NFIA binding in the olfactory bulb upon the depletion of NFIB as compared to the siRNA-scramble and wildtype controls.
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Project description:Here, we generated transcriptomes of microdissected neocortex of Nfix knockout and wildtype littermate embryos at embryonic day 16.
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Project description:Atr maintains chromosomal integrity during postnatal cerebellar neurogenesis
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2016-09-01 | GSE85393 | GEO
Project description:Microcephaly and medulloblastoma result from mutations that compromise genomic stability. We report that Atr, which is mutated in the microcephalic disorder Seckel syndrome, is required to maintain chromosomal integrity during postnatal cerebellar neurogenesis. Atr deletion in cerebellar granule neuron progenitors (CGNPs) induced proliferation-associated DNA damage, p53 activation, apoptosis, and cerebellar hypoplasia. Co-deletions of either Bax and Bak or p53 prevented apoptosis in Atr-deleted CGNPs, but failed to fully rescue cerebellar growth. Atr-deficient CGNPs showed impaired cell cycle checkpoint function and continued to proliferate, accumulating chromosomal abnormalities. RNA-Seq demonstrated that the transcriptional response to Atr-deficient proliferation was p53-driven. Acute Atr inhibition in vivo by nanoparticle-formulated VE-822 reproduced the disruptions seen with Atr deletion. Our data show that p53-driven apoptosis and senescence, and non-apoptotic cell death redundantly limit growth in Atr-deficient progenitors. These overlapping mechanisms that suppress growth in Atr-disrupted CGNPs may be exploited for treatment of CGNP-derived medulloblastoma using Atr inhibition.
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Project description:We investigated molecular changes during human, chimpanzee, and rhesus macaque postnatal brain development at the transcriptome, proteome, and metabolome levels in two brain regions: the prefrontal cortex (PFC) that is involved in several human-specific cognitive processes, and the cerebellar cortex (CBC) that may be functionally more conserved. We find a nearly three-fold excess of human-specific gene expression changes in PFC compared to CBC. The most prominent human-specific mRNA expression pattern in the PFC is a developmental delay of approximately 5 years in the expression of genes associated with learning and memory, such as synaptic transmission and long-term potentiation. This pattern is supported by correlated changes in concentrations of proteins and the respective neurotransmitters and its magnitude is beyond the shift expected from the life-histories of the species. Mechanistically, it might be driven by change in timing of expression of four or more transcription factors. We speculate that delayed synaptic maturation in PFC may play a role in the emergence of human-specific cognitive abilities. Keywords: Age series Human, chimpanzee and rhesus macaque post-mortem brain samples from the cerebellar cortex were collected. The age ranges of the individuals in all three species covered the respective species' postnatal maturation period from infancy to old adulthood. RNA extracted from the dissected tissue was hybridized to Affymetrix® Human Gene 1.0 ST arrays. CBC samples.
2011-12-09 | E-GEOD-22569 | biostudies-arrayexpress
Project description:Since the NFI transcription factors have been shown to be key regulators of gliogenesis, we utilized this pathway to identify miRNAs involved in the regulation of the neurogenesis-to-gliogenesis switch by neural stem/progenitor cells (NSPCs). We focused on miRNAs with expression levels that were differentially regulated downstream of NFIA, and established a mouse embryonic stem cell (ESC) line that expresses NFIA in a doxycycline (Dox)-dependent manner. NFIA-overexpressing (OE) and control NSPCs (neurospheres) derived from ESCs were purified from their mixed cultures (primary neursphsres (PNs) or secondary neurospheres (SNs) ) by fluorescence activated cell sorting and subjected to miRNAarray analysis.
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