Cell-specific neuropathology and multiple morphogenic mechanisms in 3D human-derived tissue
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE184878 | GEO | 2021/12/31
REPOSITORIES: GEO
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Project description:Cell-specific neuropathology and multiple morphogenic mechanisms in 3D human-derived tissue
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Project description:Pluripotent stem cells (PSC) can differentiate inot any cell type of an organism. Their remarkable capability of self-organization enables the formation of three-dimensional structures that resembles miniature organs, including cerebral organoids. These organoids can recreate early steps of the human cerebral cortex development, and show great potential for modeling human diseases, particularly for those with a developmental component. This data evidences stem cell-derived cerebral organoids as a key model to study brain development and neurodevelopmental, neurodegenerative and neuropsychiatric diseases.
2019-11-15 | PXD011605 | Pride
Project description:Cerebral organoids â three-dimensional cultures of human cerebral tissue derived from pluripotent stem cells â have emerged as models of human cortical development. However, the extent to which in vitro organoid systems recapitulate neural progenitor cell proliferation and neuronal differentiation programs observed in vivo remains unclear. Here we use single-cell RNA sequencing (scRNA-seq) to dissect and compare cell composition and progenitor-to-neuron lineage relationships in human cerebral organoids and fetal neocortex. Covariation network analysis using the fetal neocortex data reveals known and novel interactions among genes central to neural progenitor proliferation and neuronal differentiation. In the organoid, we detect diverse progenitors and differentiated cell types of neuronal and mesenchymal lineages, and identify cells that derived from regions resembling the fetal neocortex. We find that these organoid cortical cells use gene expression programs remarkably similar to those of the fetal tissue in order to organize into cerebral cortex-like regions. Our comparison of in vivo and in vitro cortical single cell transcriptomes illuminates the genetic features underlying human cortical development that can be studied in organoid cultures. 734 single-cell transcriptomes from human fetal neocortex or human cerebral organoids from multiple time points were analyzed in this study. All single cell samples were processed on the microfluidic Fluidigm C1 platform and contain 92 external RNA spike-ins. Fetal neocortex data were generated at 12 weeks post conception (chip 1: 81 cells; chip 2: 83 cells) and 13 weeks post conception (62 cells). Cerebral organoid data were generated from dissociated whole organoids derived from induced pluripotent stem cell line 409B2 (iPSC 409B2) at 33 days (40 cells), 35 days (68 cells), 37 days (71 cells), 41 days (74 cells), and 65 days (80 cells) after the start of embryoid body culture. Cerebral organoid data were also generated from microdissected cortical-like regions from H9 embryonic stem cell derived organoids at 53 days (region 1, 48 cells; region 2, 48 cells) or from iPSC 409B2 organoids at 58 days (region 3, 43 cells; region 4, 36 cells).
2015-12-07 | E-GEOD-75140 | biostudies-arrayexpress
Project description:Bulk ATAC-seq was performed on human, chimpanzee, bonobo, and macaque stem cell-derived cerebral organoids. ATAC-seq was performed on day 60 (2 months old) and day 120 (4 months old) cerebral organoids.
2019-10-16 | E-MTAB-8228 | biostudies-arrayexpress
Project description:Intestinal epithelial organoids established from resected gut tissue have become a widely used research tool. However, it remains unclear how environmental cues and other sources of variation before, during and after establishment impact on organoid properties. Divergent microbiota composition in separately held mouse lines has been identified as a confounding factor in murine in vivo studies. To probe the effect of donor microbiota on organoids, we analyzed the proteomes and transcriptomes of primary organoid cultures established from colonized and germ-free mice, and further compared them to their tissue of origin and to commonly used cell lines. The long-term global impact of donor microbiota on organoid expression patterns was negligible. Instead, stochastic culture-to-culture differences accounted for a moderate variability between independently established organoids. Integration of transcriptome and proteome datasets revealed an organoid-typic expression signature comprising 14 transcripts and 10 proteins that distinguished organoids across all donors from murine epithelial cell lines and fibroblasts. This signature, which closely mimicked expression patterns in the gut epithelium, included high levels of the inflammasome scaffold protein ASC in organoids which was lacking in commonly used cell lines. Mining of the transcriptome dataset uncovered similar high expression of also other inflammasome components, including Naip1-6, Nlrc4, and Caspase-1 in all organoids compared to the reference cell lines. Taken together, these results reveal a robust global expression pattern in organoids established from colonized and germ-free animals and suggest that organoids represent a more suitable culture model than immortalized cell lines for studies of intestinal epithelial inflammasomes.
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Project description:We used cerebral organoids generated from wildtype and CHD8 +/- human ES cells to study the effects of CHD8, one of the top ASD risk genes, on early cortical development. CHD8 +/- hESC were generated using the CRISPR/Cas9 system to create a deletion within the helicase domain. Cerebral organoids were generated according to the protocol from Lancaster et al 2013 with minor modifications.
2022-02-01 | E-MTAB-9933 | biostudies-arrayexpress
Project description:Single cell ATAC-seq (scATAC-seq) was performed on bonobo induced pluripotent stem cells (iPSC) derived cerebral organoids. scATAC-seq was performed on day 60 (2 months old cerebral organoid) and day 120 (4 months old cerebral organoid).
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Project description:Single cell ATAC-seq (scATAC-seq) was performed on macaque embryonic stem cell-derived cerebral organoids. scATAC-seq was performed on day 60 (2 months old cerebral organoid).
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Project description:During mammalian development, chromatin state differences coincide with cellular differentiation and reflect changes in the gene regulatory landscape. In the developing brain, cell fate specification and topographic identity play important roles in defining cell identity and confer selective vulnerabilities to neurodevelopmental disorders. To identify cell type specific chromatin accessibility patterns in the developing human brain, we used a single cell assay for transposase accessibility by sequencing (scATAC-seq) in primary human forebrain tissue samples. We applied unbiased analyses to identify genomic loci that undergo extensive cell type- and brain region-specific changes in accessibility during neurogenesis and an integrative analysis to predict cell type specific candidate regulatory elements. We found that cerebral organoids recapitulate most putative cell type-specific enhancer accessibility patterns but lack many cell type specific open chromatin regions found in vivo. Systematic comparison of chromatin accessibility across brain regions revealed an unexpected diversity among neural progenitor cells in the cerebral cortex and implicate retinoic acid signaling in the specification of prefrontal cortex neuronal lineage identity. Together, our results reveal the important contribution of chromatin state to the emerging patterns of cell type diversity and cell fate specification and provide a blueprint for evaluating the fidelity and robustness of cerebral organoids as a model for cortical development.
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Project description:Bovine chondrocyte-seeded and mesenchymal stem cell (MSC)-seeded agarose were cultured for 28 days in chemically defined media containing 10 ng/mL TGF-beta3. Chondrogenic differentiated MSCs were compared to chondrocytes at this timepoint and to undifferentiated MSCs harvested at day 0. Donor-matched sets of chondrocytes and MSCs were used, with three donors total.
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