Functional cortical neurons and astrocytes from human pluripotent stem cells in 3D culture
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: Daniel Geschwind
PROVIDER: E-GEOD-68917 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
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Project description:Expression profiles of human cortical spheroids (hCSs) derived from pluripotent stem cells using Illumina cDNA microarrays. The goal of the study is to assess the developmental maturity and the regional identity of those hCSs at two distinct time points with expression profiles and compare the expression pattern with in vivo data. Results show that those hCSs can map transcriptionally to in vivo fetal development.
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Project description:In vitro neural stem cell models are widely used to model a wide range of neuropsychiatric conditions. However, how well such models correspond to in vivo brain has not been evaluated in an unbiased, comprehensive manner. We used transcriptomic analyses to compare in vitro systems to developing human fetal brain and observed strong conservation of in vivo gene expression and network architecture in differentiating primary human neural progenitor cells (phNPCs). Conserved modules are enriched in genes associated with ASD, supporting the utility of phNPCs for studying neuropsychiatric disease. We also developed and validated a machine learning approach called CoNTExT that identifies the developmental maturity and regional identity of in vitro models. We observed strong differences between in vitro models, including hiPSC-derived neural progenitors from multiple laboratories. This work provides a framework for evaluating in vitro systems and supports their value in studying the molecular mechanisms of human neurodevelopmental disease. In this GEO submission, we upload data from 5 lines of phNPCs as well as hiPSCs cultured in two different laboratories all at multiple differentiation time points.
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Project description:This study uses Whole Transcriptome Shotgun Sequencing (RNA-Seq) data to interrogate the developmental dynamics of the C57BL/6 mouse liver transcriptome. We analyze gene expression patterns in the developing mouse liver over 12 distinct time points from late embryonic stage (2 days before birth) to maturity (60 days after birth). Biological functions deemed significant at different developmental stages are identified and their leverage is mapped over time. Upstream regulators modulating these gene expression patterns are determined and their regulatory networks are described along with putative transcriptional modules associated with gene regulation. Several genes that were alternatively spliced over time were identified. Previously uncharacterized isoforms were found for several genes. We analyze gene expression patterns in the developing mouse liver over 12 distinct time points from late embryonic stage (2 days before birth) to maturity (60 days after birth). Three replicates per time point.
2014-10-16 | E-GEOD-58827 | biostudies-arrayexpress
Project description:In vitro neural stem cell models are widely used to model a wide range of neuropsychiatric conditions. However, how well such models correspond to in vivo brain has not been evaluated in an unbiased, comprehensive manner. We used transcriptomic analyses to compare in vitro systems to developing human fetal brain and observed strong conservation of in vivo gene expression and network architecture in differentiating primary human neural progenitor cells (phNPCs). Conserved modules are enriched in genes associated with ASD, supporting the utility of phNPCs for studying neuropsychiatric disease. We also developed and validated a machine learning approach called CoNTExT that identifies the developmental maturity and regional identity of in vitro models. We observed strong differences between in vitro models, including hiPSC-derived neural progenitors from multiple laboratories. This work provides a framework for evaluating in vitro systems and supports their value in studying the molecular mechanisms of human neurodevelopmental disease. In this GEO submission, we upload data from 5 lines of phNPCs as well as hiPSCs cultured in two different laboratories all at multiple differentiation time points. phNPCs: For each of 5 lines generated from 3 donors (15-16 PCW), two independent differentiation experiments each containing two replicates were performed and harvested at four time points (1, 4, 8, 12 wks PD; ~16 samples per line; 77 total samples). We confirmed RNA integrity by RIN score with the Agilent 2100 Bioanalyzer (mean +/- sd: 9.16 +/- 0.78). iPSC: Two hiPSC datasets were RNA profiled as part of this study. hiPSCs grown in the Kosik lab was derived from two independent, non-isogenic IPS lines: one derived from a patient carrying a mutant Tau variant G55R and one reference control. For each of these lines, two samples were harvested at each of 0, 1, 4, and 8 weeks PD (total n=16 samples). hiPSCs grown in the Gage lab were from six samples derived from 3 control lines at each of two time points (0 and 4 wk PD, total n=12 samples). Samples were randomized to microarray chip by all biological variables of interest (donor, line, passage, replicate number, differentiation week, plate date, and RIN) to control for potential batch effects.
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Project description:The cortical area map is initially patterned by transcription factor (TF) gradients in the neocortical primordium, which define a protomap in the embryonic ventricular zone (VZ). However, mechanisms that propagate regional identity from VZ progenitors to cortical plate (CP) neurons are unknown. Here we show that the VZ, subventricular zone (SVZ), and CP contain distinct molecular maps of regional identity, reflecting different gene expression gradients in radial glia progenitors, intermediate progenitors, and projection neurons, respectively. The intermediate map in SVZ is modulated by Eomes (also known as Tbr2), a T-box TF. Eomes inactivation caused rostrocaudal shifts in SVZ and CP gene expression, with loss of corticospinal axons and gain of corticotectal projections. These findings suggest that cortical areas and connections are shaped by sequential maps of regional identity, propagated by the Pax6 ? Eomes ? Tbr1 TF cascade. In humans, PAX6, EOMES, and TBR1 have been linked to intellectual disability and autism. To determine the role of Eomes in the propagation of the protomap to cortical plate neurons, used microarray analysis of E14.5 cortex from five wild type and three Eomes knockout mice.
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Project description:The hypothalamus is a central regulator of many innate behaviors that are essential for survival, but the molecular mechanisms controlling hypothalamic patterning and cell fate specification remain poorly understood. To identify genes that control hypothalamic development, we have used single-cell RNA sequencing (scRNA-Seq) to profile mouse hypothalamic gene expression across 11 developmental time points between embryonic day 10 and postnatal day 45. This identified genes that delineated clear developmental trajectories for all major hypothalamic cell types and readily distinguished major regional subdivisions of the developing hypothalamus. We show that this approach can rapidly and comprehensively characterize mutants that control hypothalamic patterning and, in doing so, identify multiple genes that simultaneously repress posterior hypothalamic identity while promoting prethalamic identity. This argues in favor of a modified columnar organization of hypothalamus and prethalamus. These data serve as a resource for further studies of hypothalamic development, physiology, and dysfunction.
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Project description:This study uses Whole Transcriptome Shotgun Sequencing (RNA-Seq) data to interrogate the developmental dynamics of the C57BL/6 mouse liver transcriptome. We analyze gene expression patterns in the developing mouse liver over 12 distinct time points from late embryonic stage (2 days before birth) to maturity (60 days after birth). Biological functions deemed significant at different developmental stages are identified and their leverage is mapped over time. Upstream regulators modulating these gene expression patterns are determined and their regulatory networks are described along with putative transcriptional modules associated with gene regulation. Several genes that were alternatively spliced over time were identified. Previously uncharacterized isoforms were found for several genes.
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