Project description:The pituitary regulates growth, reproduction and other endocrine systems. To investigate transcriptional network epigenetic mechanisms in this gland, we generated paired single nucleus (sn) transcriptome and chromatin accessibility profiles in single mouse pituitaries, and genome-wide sn methylation datasets. Our analysis provided insight into cell type epigenetics, regulatory circuit and gene control mechanisms. Latent variable transcriptome and accessibility data representation resolved both inter-sexual and inter-individual variation in gene control programs. Multi-omics analysis of cell type-specific gene regulatory networks distinguished distinct mechanisms. Particularly, the FoxL2 gonadotrope network is controlled both by FoxL2 expression and by target gene epigenetic status. Co-accessibility analysis comprehensively identified putative regulatory regions, including a region that overlapped the fertility-linked rs11031006 human polymorphism. In vitro CRISPR-deletion at this locus increased Fshb levels, supporting this domain’s predicted regulatory role. The public pituitary atlas [link] is a resource for elucidating cell-type specific gene regulatory mechanisms and principles of transcription circuit control.
Project description:The pituitary regulates growth, reproduction and other endocrine systems. To investigate transcriptional network epigenetic mechanisms in this gland, we generated paired single nucleus (sn) transcriptome and chromatin accessibility profiles in single mouse pituitaries, and genome-wide sn methylation datasets. Our analysis provided insight into cell type epigenetics, regulatory circuit and gene control mechanisms. Latent variable transcriptome and accessibility data representation resolved both inter-sexual and inter-individual variation in gene control programs. Multi-omics analysis of cell type-specific gene regulatory networks distinguished distinct mechanisms. Particularly, the FoxL2 gonadotrope network is controlled both by FoxL2 expression and by target gene epigenetic status. Co-accessibility analysis comprehensively identified putative regulatory regions, including a region that overlapped the fertility-linked rs11031006 human polymorphism. In vitro CRISPR-deletion at this locus increased Fshb levels, supporting this domain’s predicted regulatory role. The public pituitary atlas [link] is a resource for elucidating cell-type specific gene regulatory mechanisms and principles of transcription circuit control.
Project description:The pituitary regulates growth, reproduction and other endocrine systems. To investigate transcriptional network epigenetic mechanisms in this gland, we generated paired single nucleus (sn) transcriptome and chromatin accessibility profiles in single mouse pituitaries, and genome-wide sn methylation datasets. Our analysis provided insight into cell type epigenetics, regulatory circuit and gene control mechanisms. Latent variable transcriptome and accessibility data representation resolved both inter-sexual and inter-individual variation in gene control programs. Multi-omics analysis of cell type-specific gene regulatory networks distinguished distinct mechanisms. Particularly, the FoxL2 gonadotrope network is controlled both by FoxL2 expression and by target gene epigenetic status. Co-accessibility analysis comprehensively identified putative regulatory regions, including a region that overlapped the fertility-linked rs11031006 human polymorphism. In vitro CRISPR-deletion at this locus increased Fshb levels, supporting this domain’s predicted regulatory role. The public pituitary atlas [link] is a resource for elucidating cell-type specific gene regulatory mechanisms and principles of transcription circuit control.
Project description:The pituitary regulates growth, reproduction and other endocrine systems. To investigate transcriptional network epigenetic mechanisms, we generated paired single nucleus (sn) transcriptome and chromatin accessibility profiles in single mouse pituitaries, and genome-wide sn methylation datasets. Our analysis provided insight into cell type epigenetics, regulatory circuit and gene control mechanisms. Latent variable pathway analysis detected corresponding transcriptome and chromatin accessibility programs showing both inter-sexual and inter-individual variation. Multi-omics analysis of gene regulatory networks identified regulons whose composition and function within specific cell types were shaped by the promoter accessibility state of target genes. Co-accessibility analysis comprehensively identified putative cis-regulatory regions, including a domain upstream of Fshb that overlapped the fertility-linked rs11031006 human polymorphism; In vitro CRISPR-deletion at this locus increased Fshb levels, supporting this domain’s inferred regulatory role. The sn pituitary multi-omics atlas [link] is a public resource for elucidating cell-type specific gene regulatory mechanisms and principles of transcription circuit control. This GEO series contain raw (FASTQ) and processed data (ALLC) files for the sn methylation dataset generated by the snmC-seq2 method.
Project description:To explore the mechanistic basis of the different phases of pre- and postnatal muscle development and the contraction-dependent control of muscle gene expression , we generated a multi-omics single nucleus RNAseq (snRNA-seq) and single nucleus ATAC-seq (snATAC-seq) atlas of normal muscle and paralyzed muscle from mice lacking Cacna1s.
Project description:Single nucleus pituitary transcriptomic and epigenetic landscape reveals human stem cell heterogeneity with diverse regulatory mechanisms