Search bioRxiv⌕ Search
Home/Archive/bioRxiv

bioRxiv · 10.1101/2022.12.11.519959

Single Cell transcriptional analysis of ex vivo models of cortical and hippocampal development identifies unique longitudinal trends

Krizay, D. K.·Goldstein, D. B.·Boland, M. J.
View original source ↗Export metadata ↓

Abstract

Postnatal cortical and hippocampal mouse primary neuronal cultures are powerful and widely-used models of neuronal activity and neurological disease. While this model is frequently used to recapitulate what is seen in vivo, how the transcriptomic profiles of neuronal networks change over development is not fully understood. We use single-cell transcriptomics to provide a view of neuronal network establishment and maturation. Our data highlight region-specific differences and suggest how cell populations program the transcriptome in these brain regions. We demonstrate that patterns of expression markedly differ between and within neurological diseases, and explore why these differences are found and how well they compare to other models. In particular, we show significant expression differences between genes associated with epilepsy, autism spectrum disorder, and other neurological disorders. Collectively, our study provides novel insights on this popular model of development and disease that will better inform design for drug discovery and therapeutic intervention. O_FIG O_LINKSMALLFIG WIDTH=153 HEIGHT=200 SRC="FIGDIR/small/519959v1_ufig1.gif" ALT="Figure 1"> View larger version (38K): org.highwire.dtl.DTLVardef@1be59a3org.highwire.dtl.DTLVardef@1ef18b9org.highwire.dtl.DTLVardef@402c1dorg.highwire.dtl.DTLVardef@1103789_HPS_FORMAT_FIGEXP M_FIG O_FLOATNOGraphical AbstractC_FLOATNO (A) Schematic representing select gene expression progression through neuronal network maturation from human cortical organoids (3- and 6-Month Organoid), newborn mice (P0 Mouse), immature ex vivo cortex derived cultures (DIV 3 ex vivo), functionally mature ex vivo cortex derived cultures (DIV15-31 ex vivo), and adult mice (P56 Mouse). Color represents proportion of excitatory neurons with detectable expression for selected representative genes Mapk10, Igfbp2, which increase and decrease through network maturation, respectively. (B) Schematic representing divergent expression patterns between genes associated with epilepsy and ASD through network maturation between the organoids and ex vivo cultures shown in (A). Color scales represent the change in the percentile, in respect to all genes, of the proportion of excitatory neurons with detectable expression. C_FIG

Explore related subjects

geneticsPreprint

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Krizay, D. K., Goldstein, D. B., Boland, M. J.. 2022-12-12. Single Cell transcriptional analysis of ex vivo models of cortical and hippocampal development identifies unique longitudinal trends. https://doi.org/10.1101/2022.12.11.519959

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

bioRxiv2026

Large language model-based bibliometric evaluation of population descriptors in human genetics

As the use of population descriptors such as race, ethnicity, and ancestry have become increasingly common in modern genetics research, there have been growing calls to critically examine their use. Most notably, in 2023, the National Academies of Science, Engineering, and Medicine (NASEM) published a report titled Using Population Descriptors in Genetics and Genomics Research: A New Framework for an Evolving Field, which included eight specific and actionable recommendations for researchers to implement the ethical and accurate use of population descriptors in genetic research. Here, we use the 2023 NASEM report as a benchmark to analyze the use of population descriptors in genome-wide association studies (GWAS). We develop a general toolkit for large language model-based bibliometrics, operationalize the report's recommendations into an evaluation framework, and apply this framework to evaluate all 4,007 papers from the GWAS Catalog published between 2007 and 2025 with full text available on PubMedCentral. We find significant improvements in adherence to NASEM report recommendations over time. However, most improvements predate the publication of the NASEM report itself, suggesting the report functioned primarily as a synthesis of existing best practices rather than a catalyst for change. We conclude by highlighting opportunities for growth in the field of human genetics.

genetics↗
bioRxiv2026

Mitigating biases of rescaling in forward-in-time population genetic simulations

Forward-in-time population genetic simulations are widely used in evolutionary analyses, but simulating large populations and long genomic regions remains computationally demanding. To reduce this cost, parameter rescaling is widely employed, in which the original evolutionary process is approximated by one with a smaller population size and fewer generations. Recently, several studies using the SLiM simulator have raised concerns about the accuracy of this rescaling approach. In this study, we show that many of the biases reported in these studies can be mitigated by using a different simulation algorithm. These results reveal that the accuracy of parameter rescaling depends on how well the simulation algorithm preserves diffusion-limit properties under rescaling.

genetics↗
bioRxiv2026

OPA1 controls mitochondrial dysfunction-driven liver fibrosis in MASLD

Progressive hepatic fibrosis is the principal determinant of morbidity and mortality in metabolic dysfunction-associated steatotic liver disease and steatohepatitis (MASLD/MASH). Mitochondrial dysfunction is a hallmark of MASH, and the release of mitochondrial damage-associated molecular patterns (mito-DAMPs) from injured hepatocytes can promote fibrosis. However, how mitochondrial dynamics and quality control shape the fibrotic response in MASLD/MASH remains unclear. Here, through large-scale genomic analyses of mitochondrial genes governing mitophagy, fusion and fission in human MASLD, with a power-equivalent sample size of approximately 700,000 individuals, we identify a strong association between hepatic fibrosis and the mitochondrial fusion factor dynamin-like GTPase optic atrophy 1 (OPA1). OPA1 transcripts and protein abundance in the liver epithelium were progressively dysregulated with advancing fibrosis. In mice, hepatocyte-specific OPA1 loss alone was sufficient to induce hepatic stellate cell activation and fibrosis in zone 3, promoted the release of mito-DAMPs into the circulation and exacerbated fibrosis in experimental MASH. These findings identify OPA1 as a central regulator of the hepatic fibrotic response and connect defective mitochondrial homeostasis to mito-DAMP release, hepatic stellate cell activation and fibrosis in MASLD.

genetics↗