Human neuron subtype programming through combinatorial patterning with scSeq readouts
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ABSTRACT:
PROVIDER: PRJNA1049739 | ENA |
REPOSITORIES: ENA
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Project description:iPSCs were induced into neuronal fate using either NGN2 or ACL1/DLX2 under different conditions. Single-cell RNA-sequencing was used to measure diversity of acquired neuronal fates. Single-cell multiome (RNA+ATAC) was performed on patterned iPSCs.
2025-07-15 | GSE249572 | GEO
Project description:Combinatorial transcriptional regulation establishes subtype-appropriate synaptic properties in auditory neurons
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Project description:In vitro generation of human peripheral sensory neurons may provide a framework for novel drug screening platforms and disease models of touch and pain. However, derivation of a functionally pure sensory neuron population remains a major unmet challenge. We discovered that, by expressing the transcription factors NGN2 and BRN3A, human pluripotent stem cells can be induced to differentiate into a surprisingly homogenous culture of cold- and mechano-sensing neurons. Although such a neuronal subtype has not been reported in mice, we found molecular evidence of its existence in adult human sensory ganglia. Combining NGN2 and BRN3A programming with neural crest patterning, we produced two additional populations of sensory neurons, including a more specialized mechanosensory neuron subtype. Finally, we applied this system to model a rare inherited sensory disorder, characterized by profound impairment of touch sensation and proprioception, caused by inactivating mutations in PIEZO2. Together these findings establish an approach to specify distinct sensory neuron subtypes in vitro, underscoring the utility of stem cell technology to capture human-specific features of physiology and disease.
2020-01-21 | GSE139273 | GEO
Project description:In vitro generation of human peripheral sensory neurons may provide a framework for novel drug screening platforms and disease models of touch and pain. However, derivation of a functionally pure sensory neuron population remains a major unmet challenge. We discovered that, by expressing the transcription factors NGN2 and BRN3A, human pluripotent stem cells can be induced to differentiate into a surprisingly homogenous culture of cold- and mechano-sensing neurons. Although such a neuronal subtype has not been reported in mice, we found molecular evidence of its existence in adult human sensory ganglia. Combining NGN2 and BRN3A programming with neural crest patterning, we produced two additional populations of sensory neurons, including a more specialized mechanosensory neuron subtype. Finally, we applied this system to model a rare inherited sensory disorder, characterized by profound impairment of touch sensation and proprioception, caused by inactivating mutations in PIEZO2. Together these findings establish an approach to specify distinct sensory neuron subtypes in vitro, underscoring the utility of stem cell technology to capture human-specific features of physiology and disease.
2019-12-31 | GSE139409 | GEO
Project description:Hundreds of Chromatin Regulators (CRs) control chromatin structure and function by catalyzing and binding histone modifications, yet the rules governing these key processes remain obscure. Here, we present a systematic approach to infer CR function. We developed ChIP-string, a meso-scale assay that combines chromatin immunoprecipitation with a signature readout of 487 representative loci. We applied ChIP-string to screen 145 antibodies, thereby identifying effective reagents, which we used to map the genome-wide binding of 29 CRs in two cell types. We found that specific combinations of CRs co-localize in characteristic patterns at distinct chromatin environments, genes of coherent functions and distal regulatory elements. When comparing between cell types, CRs redistribute to different loci, but maintain their modular and combinatorial associations. Our work provides a multiplex method that substantially enhances the ability to monitor CR binding, presents a large resource of CR maps, and reveals common principles for combinatorial CR function. For data usage terms and conditions, please refer to http://www.genome.gov/27528022 and http://www.genome.gov/Pages/Research/ENCODE/ENCODEDataReleasePolicyFinal2008.pdf Study of genom-wide binding of 29 CRs in two cell types.
2011-12-23 | E-GEOD-32509 | biostudies-arrayexpress
Project description:Background: Spermatogonial stem cells (SSCs) sustain the process of steady-state spermatogenesis in the mammalian testis, which is critical to the ongoing production of sperm and male fertility. SSCs can both self-renew to perpetuate the SSC population, and give rise to progenitors to propel the spermatogenic differentiation pathway. SSCs are detectable as a small subpopulation of undifferentiated spermatogonia that demonstrate regenerative capacity in a transplantation assay, and can be selectively recovered on the basis of expression of an Id4-eGfp sortable marker transgene. Enriched populations of SSCs and progenitors display consistent differences in gene expression patterns suggesting they represent discrete spermatogonial subtypes. Results: Here we describe distinct spermatogonial subtype-specific epigenetic programming profiles associated with subtype-specific differential gene expression on the basis of genome-wide patterns of six different histone modifications, chromatin accessibility, and DNA methylation. We find that similarly expressed genes show no differences in epigenetic programming, whereas differentially expressed genes show distinct histone modification patterns as well as subtype-specific differences in patterns of distal intergenic low-methylated regions. Motif-enrichment analysis of differentially programmed elements predicts a set of transcription factors that may regulate this spermatogonial subtype-specific epigenetic programming, and gene-specific chromatin immunoprecipitation analyses confirm subtype-specific differences in binding of a subset of these factors to target genes. Conclusions: Taken together, these results indicate that SSCs and progenitors are discrete spermatogonial subtypes that appear to be differentially programmed to carry out mutually exclusive functions including self-renewal and maintenance of regenerative capacity in SSCs and lineage commitment and loss of regenerative capacity in progenitors.
2019-05-23 | GSE131656 | GEO
Project description:Background: Spermatogonial stem cells (SSCs) sustain the process of steady-state spermatogenesis in the mammalian testis, which is critical to the ongoing production of sperm and male fertility. SSCs can both self-renew to perpetuate the SSC population, and give rise to progenitors to propel the spermatogenic differentiation pathway. SSCs are detectable as a small subpopulation of undifferentiated spermatogonia that demonstrate regenerative capacity in a transplantation assay, and can be selectively recovered on the basis of expression of an Id4-eGfp sortable marker transgene. Enriched populations of SSCs and progenitors display consistent differences in gene expression patterns suggesting they represent discrete spermatogonial subtypes. Results: Here we describe distinct spermatogonial subtype-specific epigenetic programming profiles associated with subtype-specific differential gene expression on the basis of genome-wide patterns of six different histone modifications, chromatin accessibility, and DNA methylation. We find that similarly expressed genes show no differences in epigenetic programming, whereas differentially expressed genes show distinct histone modification patterns as well as subtype-specific differences in patterns of distal intergenic low-methylated regions. Motif-enrichment analysis of differentially programmed elements predicts a set of transcription factors that may regulate this spermatogonial subtype-specific epigenetic programming, and gene-specific chromatin immunoprecipitation analyses confirm subtype-specific differences in binding of a subset of these factors to target genes. Conclusions: Taken together, these results indicate that SSCs and progenitors are discrete spermatogonial subtypes that appear to be differentially programmed to carry out mutually exclusive functions including self-renewal and maintenance of regenerative capacity in SSCs and lineage commitment and loss of regenerative capacity in progenitors.
2019-05-23 | GSE131655 | GEO
Project description:Background: Spermatogonial stem cells (SSCs) sustain the process of steady-state spermatogenesis in the mammalian testis, which is critical to the ongoing production of sperm and male fertility. SSCs can both self-renew to perpetuate the SSC population, and give rise to progenitors to propel the spermatogenic differentiation pathway. SSCs are detectable as a small subpopulation of undifferentiated spermatogonia that demonstrate regenerative capacity in a transplantation assay, and can be selectively recovered on the basis of expression of an Id4-eGfp sortable marker transgene. Enriched populations of SSCs and progenitors display consistent differences in gene expression patterns suggesting they represent discrete spermatogonial subtypes. Results: Here we describe distinct spermatogonial subtype-specific epigenetic programming profiles associated with subtype-specific differential gene expression on the basis of genome-wide patterns of six different histone modifications, chromatin accessibility, and DNA methylation. We find that similarly expressed genes show no differences in epigenetic programming, whereas differentially expressed genes show distinct histone modification patterns as well as subtype-specific differences in patterns of distal intergenic low-methylated regions. Motif-enrichment analysis of differentially programmed elements predicts a set of transcription factors that may regulate this spermatogonial subtype-specific epigenetic programming, and gene-specific chromatin immunoprecipitation analyses confirm subtype-specific differences in binding of a subset of these factors to target genes. Conclusions: Taken together, these results indicate that SSCs and progenitors are discrete spermatogonial subtypes that appear to be differentially programmed to carry out mutually exclusive functions including self-renewal and maintenance of regenerative capacity in SSCs and lineage commitment and loss of regenerative capacity in progenitors.
2019-05-23 | GSE131654 | GEO
Project description:Background: Spermatogonial stem cells (SSCs) sustain the process of steady-state spermatogenesis in the mammalian testis, which is critical to the ongoing production of sperm and male fertility. SSCs can both self-renew to perpetuate the SSC population, and give rise to progenitors to propel the spermatogenic differentiation pathway. SSCs are detectable as a small subpopulation of undifferentiated spermatogonia that demonstrate regenerative capacity in a transplantation assay, and can be selectively recovered on the basis of expression of an Id4-eGfp sortable marker transgene. Enriched populations of SSCs and progenitors display consistent differences in gene expression patterns suggesting they represent discrete spermatogonial subtypes. Results: Here we describe distinct spermatogonial subtype-specific epigenetic programming profiles associated with subtype-specific differential gene expression on the basis of genome-wide patterns of six different histone modifications, chromatin accessibility, and DNA methylation. We find that similarly expressed genes show no differences in epigenetic programming, whereas differentially expressed genes show distinct histone modification patterns as well as subtype-specific differences in patterns of distal intergenic low-methylated regions. Motif-enrichment analysis of differentially programmed elements predicts a set of transcription factors that may regulate this spermatogonial subtype-specific epigenetic programming, and gene-specific chromatin immunoprecipitation analyses confirm subtype-specific differences in binding of a subset of these factors to target genes. Conclusions: Taken together, these results indicate that SSCs and progenitors are discrete spermatogonial subtypes that appear to be differentially programmed to carry out mutually exclusive functions including self-renewal and maintenance of regenerative capacity in SSCs and lineage commitment and loss of regenerative capacity in progenitors.
2019-05-23 | GSE131653 | GEO