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RNA-seq of murine proliferating neural stem and progenitor cells from Kat7-deleted mouse fetuses

ABSTRACT: RNA-seq of murine proliferating neural stem and progenitor cells from Kat7-deleted mouse fetuses

PROVIDER: PRJNA910081 | ENA |

REPOSITORIES: ENA

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RNA-seq of murine proliferating neural stem and progenitor cells from Kat7-deleted mouse fetuses

Project description:Tissue-specific deletion of the gene encoding the histone acetyltransferase Kat7 (Hbo1) in the developing mouse central nervous system using cre-recombinase expression driven by regulatory sequences of the nestin locus (NesCre transgene) resulted in defective cerebral cortex development, a complete failure of neural stem cells to give rise to neurons and oligodendrocytes during in vitro differentiation, and a failure to express the neuronal differentiation program. Proliferating neural stem and progenitor cells (NPSCs) were isolated from Kat7-deleted and Kat7-intact 14.5 day embryonic mouse fetuses.

2022-12-09 | GSE220498 | GEO

Chromatin immunoprecipitation and high-throughput sequencing (ChIP-seq) detection of histone H3 lysine 14 acetylation (H3K14ac) and KAT7 (HBO1) in E14.5 mouse neural stem and progenitor cells (NSPCs)

Project description:Tissue specific deletion of the gene encoding the histone acetyltransferase KAT7 (HBO1) in the developing mouse central nervous system using cre-recombinase expression driven by regulatory sequences of the nestin locus (NesCre transgene) resulted in defective cerebral cortex development, a complete failure of neural stem cells to give rise to neurons and oligodendrocytes during in vitro differentiation and a failure to express the neuronal differentiation program. KAT7 genome occupancy and histone H3 lysine 14 acetylation (H3K14ac) levels were assessed by ChIP-seq in proliferating Kat7 deleted vs. Kat7 intact neural stem and progenitor cells (NSPCs). KAT7 and H3K14ac were completely absent in the Kat7 deleted cells. IN KAT7 intact cells, KAT7 occupancy levels and H3K14ac levels within the body of genes correlated strongly and positively. Both were higher in genes that were expressed strongly than in genes with lower or no expression. However, KAT7 and H3K14ac were present in all genes including silent genes and in all other regions of the genome, including intergenic regions and regions decorated with histone H3 lysine 9 trimethylation (H3K9me3), an indicator of constitutive heterochromatin.

2022-11-30 | GSE216459 | GEO

Effects of loss of the histone lysine acetyltransferase KAT7 on mRNA levels in proliferating and differentiating mouse neural stem cells (neurosphere cells) [RNA-seq]

Project description:RNA-seq data of neural stem and progenitor cell (NSPC) isolates from Kat7lox/loxNesCreT/+ and Kat7+/+NesCreT/+ E14.5 foetuses for each, proliferating and differentiating conditions. KAT7 and H3K14ac were not required for the continued transcription of genes that were actively transcribed at the time of loss of KAT7, but indispensable for the activation of repressed genes.

2022-11-30 | GSE215970 | GEO

Stem cell plasticity, acetylation of H3K14 and de novo gene activation rely on KAT7

Project description:In the conventional model of transcriptional activation, transcription factors bind to response elements and recruit co-factors, including histone acetyltransferases. Contrary to this model, we show that the histone acetyltransferase KAT7 (HBO1/MYST2) is required genome-wide for histone H3 lysine 14 acetylation (H3K14ac). Examining neural stem cells, we found that KAT7 and H3K14ac were present not only at transcribed genes, but also at inactive genes, intergenic regions and in heterochromatin. KAT7 and H3K14ac were not required for the continued transcription of genes that were actively transcribed at the time of loss of KAT7, but indispensable for the activation of repressed genes. The absence of KAT7 abrogated neural stem cell plasticity, diverse differentiation pathways and cerebral cortex development. Reexpression of KAT7 restored stem cell developmental potential. Overexpression of KAT7 enhanced neuron and oligodendrocyte differentiation. Our data suggest that KAT7 prepares chromatin for transcriptional activation and is a prerequisite for gene activation.

2022-12-09 | GSE220602 | GEO

KAT7 promotes malignant phenotypes of colorectal cancer via MRAS-mediated activation of the MAPK/ERK pathway

Project description:Histone acetyltransferases (HATs) play a crucial role in transcriptional regulation by acetylating histones. Dysregulation of HAT activity is implicated in developmental disorders and cancer. In this study, we discovered an upregulated KAT7 signaling pathway in colorectal cancer (CRC) and its association with poor patient survival. Knockdown of KAT7 suppressed CRC cell viability, proliferation, migration, and invasion while promoting apoptosis. Conversely, KAT7 overexpression enhanced these cellular processes. In vivo experiments demonstrated that KAT7 knockdown inhibited CRC growth and lung metastasis. Mechanistically, KAT7 acetylated histone H3 at lysine 14 (H3K14) to enhance MRAS transcription, which activated the MAPK/ERK pathway and promoted tumorigenesis. Overexpression of MRAS or treatment with the ERK activator C6 Ceramide rescued the tumor inhibition caused by KAT7 silencing. The acetyltransferase activity of KAT7 is essential for CRC progression. Reexpression of KAT7, but not KAT7 acetyltransferase activity-deficient mutants, rescued MRAS expression, ERK phosphorylation, and CRC tumorigenesis in KAT7 knockdown CRC cells. Taken together, our results define the essential role of KAT7 in CRC tumorigenesis, rationalizing its potential as a therapeutic target for CRC treatment.

2024-06-27 | GSE270298 | GEO

miRNA Expression data from the differentiating and proliferating neural stem/progenitor cells

Project description:The adverse effect of CSDS on the DG neurogenesis is expected to affect the properties of the resident NSCs/NPCs.We used neurosphere culture system, a well-established ex vivo model to study neurogenesis. We collected proliferating neurospheres and differentiating NSCs/NPCs after 7 days of plating and isolated RNA for microRNA array to identify the altered miRNAs

2019-07-17 | GSE132822 | GEO

Gene Expression data from the differentiating and proliferating neural stem/progenitor cells

Project description:The adverse effect of CSDS on the DG neurogenesis is expected to affect the properties of the resident NSCs/NPCs.We used neurosphere culture system, a well-established ex vivo model to study neurogenesis. We collected proliferating neurospheres and differentiating NSCs/NPCs from two stages, i.e. early (after 2 days) and late (after 7 days) and isolated RNA for gene arrays.

2019-07-17 | GSE132820 | GEO

A Genome-wide CRISPR-Based Screen Identifies KAT7 as a Senescence Driver

Project description:Understanding the genetic and epigenetic bases of cellular senescence is instrumental to aging intervention. We performed genome-wide CRISPR/Cas9-based screens in two human mesenchymal precursor cell (hMPC) models of progeroid syndromes and identified hundreds of genes whose deficiency alleviated cellular senescence. Among them, KAT7, a histone acetyltransferase, ranked as a top hit in both models. Inactivation of KAT7 decreased H3 lysine 14 acetylation (H3K14ac), repressed p15INK4b transcription, and rejuvenated both physiologically and pathologically aged cells. Moreover, lentiviral vectors encoding Cas9/sg-Kat7 alleviated liver senescence and extended healthspan and lifespan of mice. Our findings demonstrate that CRISPR/Cas9-based genetic screening is a robust method for systematically uncovering unknown senescence genes, of which KAT7 may represent a new therapeutic target for aging intervention.

2020-10-09 | GSE124197 | GEO

Expression data from proliferating and quiescent adult hippocampal neural stem and progenitor cells

Project description:We have characterized the transcriptome of adult rat hippocampal neural stem and progenitor cell (NSPC) cultures. The NSPCs cultures can be reversibly arrested by the quiescence-promoting signal BMP4. We provide expression data from NSPCs grown as neurospheres for 4 days in vitro in the presence of FGF2 (proliferating NSPCs) or FGF2+BMP4 (quiescent NSPCs) showing that entry into quiescence involves major changes in the transcriptional profile of the cells.

2020-09-29 | GSE158658 | GEO

Effects of loss of the histone lysine acetyltransferase KAT7 on mRNA levels in proliferating and differentiating mouse neural stem cells (neurosphere cells) [RNA-seq]

Project description:Effects of loss of the histone lysine acetyltransferase KAT7 on mRNA levels in proliferating and differentiating mouse neural stem cells (neurosphere cells) [RNA-seq]

| PRJNA891365 | ENA

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