Similar Datasets
Project description:Down syndrome, caused by an extra copy of chromosome 21, is the most common genetic form of intellectual disability affecting up to 1 in 700 live births1-3. Yet, it remains unclear how the increased dosage of ~200 protein-coding genes on chromosome 21 affects brain development, particularly in the cerebral cortex—the area central to higher-level cognitive functions4-7. Here we generated a single-cell transcriptome and chromatin accessibility atlas from 30 human fetal cortical samples at mid gestation (10-20 weeks after conception), a critical period of cortical development8. We discovered an early global transcriptional network disruption, subtly altering ~600 genes involved in neural development and function, mostly in excitatory neurons accompanied by a significant reduction in RORB/FOXP1 expressing excitatory neurons. Multimodal network analyses predicted the chromosome 21 transcription factors BACH1, PKNOX1, and GABPA as key regulatory hubs controlling dozens of genes genetically linked to intellectual disability. Antisense-mediated normalization of the increased activity of these transcription factors in stem-cell-derived neural cells in vitro, which partially recapitulated molecular changes in the Down syndrome cortex, rescued expression of several of these predicted intellectual disability-associated targets. Finally, a humanized in vivo model replicates key molecular features of Down syndrome not recapitulated in neural cells in vitro. This resource defines the gene-regulatory landscape of the developing human cortex in Down syndrome, revealing early molecular and cellular signatures and candidate therapeutic targets, along with a human in vivo experimental platform for their preclinical testing.
2025-12-23 | GSE305146 | GEO
Project description:Single-Cell Multiomic Atlas of Human Cortical Development in Down Syndrome
| PRJNA1304507 | ENA
Project description:Down syndrome, caused by an extra copy of chromosome 21, is the most common genetic form of intellectual disability, which affects up to 1 in 700 live births. Yet, how increased dosage of the ~200 protein-coding genes on human chromosome 21 affects cortical development and function remains unclear. Here we generated a single-cell transcriptome and chromatin accessibility atlas of the human foetal cortex at mid gestation (11-20 weeks after conception), a critical period of cortical development. We uncovered an early global transcriptional network disruption, subtly altering ~1000 genes involved in neural development and function primarily in excitatory neurons. These changes reflected clinical phenotypes like intellectual disability and epilepsy, were accompanied by a significant reduction in layer 4 neurons, and were driven by a network of transcription factors including chromosome 21 genes BACH1, PKNOX1, and GABPA. Finally, a xenograft model replicates key molecular features, offering an experimental platform for validating new therapeutic targets. This resource defines the gene-regulatory landscape of the developing human cortex in Down syndrome, revealing the earliest known molecular and cellular signatures of its neurological manifestations and novel candidate targets for therapeutic interventions.
2025-12-23 | GSE305139 | GEO
Project description:Down syndrome, caused by an extra copy of chromosome 21, is the most common genetic form of intellectual disability affecting up to 1 in 700 live births1-3. Yet, it remains unclear how the increased dosage of ~200 protein-coding genes on chromosome 21 affects brain development, particularly in the cerebral cortex—the area central to higher-level cognitive functions4-7. Here we generated a single-cell transcriptome and chromatin accessibility atlas from 30 human fetal cortical samples at mid gestation (10-20 weeks after conception), a critical period of cortical development8. We discovered an early global transcriptional network disruption, subtly altering ~600 genes involved in neural development and function, mostly in excitatory neurons accompanied by a significant reduction in RORB/FOXP1 expressing excitatory neurons. Multimodal network analyses predicted the chromosome 21 transcription factors BACH1, PKNOX1, and GABPA as key regulatory hubs controlling dozens of genes genetically linked to intellectual disability. Antisense-mediated normalization of the increased activity of these transcription factors in stem-cell-derived neural cells in vitro, which partially recapitulated molecular changes in the Down syndrome cortex, rescued expression of several of these predicted intellectual disability-associated targets. Finally, a humanized in vivo model replicates key molecular features of Down syndrome not recapitulated in neural cells in vitro. This resource defines the gene-regulatory landscape of the developing human cortex in Down syndrome, revealing early molecular and cellular signatures and candidate therapeutic targets, along with a human in vivo experimental platform for their preclinical testing.
2025-12-23 | GSE305145 | GEO
Project description:Down syndrome, caused by an extra copy of chromosome 21, is the most common genetic form of intellectual disability affecting up to 1 in 700 live births1-3. Yet, it remains unclear how the increased dosage of ~200 protein-coding genes on chromosome 21 affects brain development, particularly in the cerebral cortex—the area central to higher-level cognitive functions4-7. Here we generated a single-cell transcriptome and chromatin accessibility atlas from 30 human fetal cortical samples at mid gestation (10-20 weeks after conception), a critical period of cortical development8. We discovered an early global transcriptional network disruption, subtly altering ~600 genes involved in neural development and function, mostly in excitatory neurons accompanied by a significant reduction in RORB/FOXP1 expressing excitatory neurons. Multimodal network analyses predicted the chromosome 21 transcription factors BACH1, PKNOX1, and GABPA as key regulatory hubs controlling dozens of genes genetically linked to intellectual disability. Antisense-mediated normalization of the increased activity of these transcription factors in stem-cell-derived neural cells in vitro, which partially recapitulated molecular changes in the Down syndrome cortex, rescued expression of several of these predicted intellectual disability-associated targets. Finally, a humanized in vivo model replicates key molecular features of Down syndrome not recapitulated in neural cells in vitro. This resource defines the gene-regulatory landscape of the developing human cortex in Down syndrome, revealing early molecular and cellular signatures and candidate therapeutic targets, along with a human in vivo experimental platform for their preclinical testing.
2025-12-23 | GSE305140 | GEO
Project description:Down syndrome, caused by an extra copy of chromosome 21, is the most common genetic form of intellectual disability, which affects up to 1 in 700 live births. Yet, how increased dosage of the ~200 protein-coding genes on human chromosome 21 affects cortical development and function remains unclear. Here we generated a single-cell transcriptome and chromatin accessibility atlas of the human foetal cortex at mid gestation (11-20 weeks after conception), a critical period of cortical development. We uncovered an early global transcriptional network disruption, subtly altering ~1000 genes involved in neural development and function primarily in excitatory neurons. These changes reflected clinical phenotypes like intellectual disability and epilepsy, were accompanied by a significant reduction in layer 4 neurons, and were driven by a network of transcription factors including chromosome 21 genes BACH1, PKNOX1, and GABPA. Finally, a xenograft model replicates key molecular features, offering an experimental platform for validating new therapeutic targets. This resource defines the gene-regulatory landscape of the developing human cortex in Down syndrome, revealing the earliest known molecular and cellular signatures of its neurological manifestations and novel candidate targets for therapeutic interventions.
2025-12-23 | GSE305135 | GEO
Project description:Cis-regulatory elements (CREs) precisely control spatiotemporal gene expression in cells. Using a spatially resolved single-cell atlas of gene expression with chromatin accessibility across ten soybean tissues, we identified 103 distinct cell types and 303,199 accessible chromatin regions (ACRs). Nearly 40% of the ACRs showed cell-type-specific patterns and were enriched for transcription factor (TF) motifs defining diverse cell identities. We identified de novo enriched TF motifs and explored conservation of gene regulatory networks underpinning legume symbiotic nitrogen fixation. With comprehensive developmental trajectories for endosperm and embryo, we uncovered the functional transition of the three sub-cell types of endosperm, identified 13 sucrose transporters sharing the DOF11 motif that were co-up-regulated in late peripheral endosperm and identified key embryo cell-type specification regulators during embryogenesis, including a homeobox TF that promotes cotyledon parenchyma identity. This resource provides a valuable foundation for analyzing gene regulatory programs in soybean cell types across tissues and life stages.
| S-EPMC11244997 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below.
2024-01-25 | GSE196447 | GEO
Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series
2013-08-06 | E-GEOD-42144 | biostudies-arrayexpress
Project description:This SuperSeries is composed of the SubSeries listed below.
2009-02-23 | GSE14105 | GEO