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Single-cell RNA-seq of undirected human cerebral organoids (HuCOs) infected with MV1 or MV2 compared with uninfected controls at 120 and 180 days post-infection

ABSTRACT: Undirected human cerebral organoids (HuCOs) derived from induced pluripotent stem cells (hiPSCs) were used to model neural development and infection response in vitro. Organoids were maintained in spinning bioreactors and divided into three experimental groups: MV1-infected, MV2-infected, and uninfected control (NBH). Each infection group was harvested at two developmental stages, approximately 120 and 180 days post-infection (dpi), following five months of infection. Single-cell RNA-seq libraries were prepared using the 10x Genomics Chromium Next GEM Single Cell 3′ Reagent Kits v3.1 and sequenced on an Illumina NovaSeq 6000 platform. The study aimed to characterize infection-induced transcriptional and cellular changes across time points and between infection subtypes. This dataset provides a high-resolution single-cell transcriptomic resource to explore cellular heterogeneity and host–pathogen interactions in undirected human cerebral organoids.

ORGANISM(S): Homo sapiens

PROVIDER: GSE309815 | GEO | 2025/11/18

REPOSITORIES: GEO

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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).

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Single-cell RNA-seq of undirected human cerebral organoids (HuCOs) infected with MV1 or MV2 compared with uninfected controls at 120 and 180 days post-infection

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