Y Chromosome Genes May Play Roles in the Development of Neural Rosettes from Human Embryonic Stem Cells

Khani, Farzaneh; Nafian, Simin; Mollamohammadi, Sepideh; Nemati, Shiva; Shokoohian, Bahare; Hassani, Seyedeh‐Nafiseh; Baharvand, Hossein; Soleimanpour‐Lichaei, Hamid Reza; Salekdeh, Ghasem Hosseini

doi:10.1007/s12015-022-10392-2

Cited by 4 publications

(1 citation statement)

References 50 publications

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“…RPS4Y1 is a ribosomal protein and thus involved in the synthesis of proteins. Its function in neuronal development is not fully understood; however, it is expressed in the developing and mature brain (Weickert et al, 2009;Kang et al, 2011;Shi et al, 2016;Khani et al, 2022). Moreover, it is reported to play a role in neuronal differentiation (Vakilian et al, 2015), which is supported by our results, specifically in an advanced stage of neuronal induction.…”

Section: Genetic Sex Differences Are Not Routinely Investigatedsupporting

confidence: 83%

Sex-biased gene expression during neural differentiation of human embryonic stem cells

Pottmeier,

Nikolantonaki,

Lanner

et al. 2024

Front. Cell Dev. Biol.

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Sex differences in the developing human brain are primarily attributed to hormonal influence. Recently however, genetic differences and their impact on the developing nervous system have attracted increased attention. To understand genetically driven sexual dimorphisms in neurodevelopment, we investigated genome-wide gene expression in an in vitro differentiation model of male and female human embryonic stem cell lines (hESC), independent of the effects of human sex hormones. Four male and four female-derived hESC lines were differentiated into a population of mixed neurons over 37 days. Differential gene expression and gene set enrichment analyses were conducted on bulk RNA sequencing data. While similar differentiation tendencies in all cell lines demonstrated the robustness and reproducibility of our differentiation protocol, we found sex-biased gene expression already in undifferentiated ESCs at day 0, but most profoundly after 37 days of differentiation. Male and female cell lines exhibited sex-biased expression of genes involved in neurodevelopment, suggesting that sex influences the differentiation trajectory. Interestingly, the highest contribution to sex differences was found to arise from the male transcriptome, involving both Y chromosome and autosomal genes. We propose 13 sex-biased candidate genes (10 upregulated in male cell lines and 3 in female lines) that are likely to affect neuronal development. Additionally, we confirmed gene dosage compensation of X/Y homologs escaping X chromosome inactivation through their Y homologs and identified a significant overexpression of the Y-linked demethylase UTY and KDM5D in male hESC during neuron development, confirming previous results in neural stem cells. Our results suggest that genetic sex differences affect neuronal differentiation trajectories, which could ultimately contribute to sex biases during human brain development.

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Section: Genetic Sex Differences Are Not Routinely Investigatedsupporting

confidence: 83%

Sex-biased gene expression during neural differentiation of human embryonic stem cells

Pottmeier,

Nikolantonaki,

Lanner

et al. 2024

Front. Cell Dev. Biol.

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Genomic insights and advanced machine learning: characterizing autism spectrum disorder biomarkers and genetic interactions

Nahas,

Datta,

Alsamman

et al. 2023

Metab Brain Dis

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Autism Spectrum Disorder (ASD) is a complex neurodevelopmental condition characterized by altered brain connectivity and function. In this study, we employed advanced bioinformatics and explainable AI to analyze gene expression associated with ASD, using data from five GEO datasets. Among 351 neurotypical controls and 358 individuals with autism, we identified 3,339 Differentially Expressed Genes (DEGs) with an adjusted p-value (≤ 0.05). A subsequent meta-analysis pinpointed 342 DEGs (adjusted p-value ≤ 0.001), including 19 upregulated and 10 down-regulated genes across all datasets. Shared genes, pathogenic single nucleotide polymorphisms (SNPs), chromosomal positions, and their impact on biological pathways were examined. We identified potential biomarkers (HOXB3, NR2F2, MAPK8IP3, PIGT, SEMA4D, and SSH1) through text mining, meriting further investigation. Additionally, ‎we shed light on the roles of RPS4Y1 and KDM5D genes in neurogenesis and neurodevelopment. Our analysis detected 1,286 SNPs linked to ASD-related conditions, of which 14 high-risk SNPs were located on chromosomes 10 and X. We highlighted potential missense SNPs associated with FGFR inhibitors, suggesting that it may serve as a promising biomarker for responsiveness to targeted therapies. Our explainable AI model identified the MID2 gene as a potential ASD biomarker. This research unveils vital genes and potential biomarkers, providing a foundation for novel gene discovery in complex diseases.

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Complete analysis of G-quadruplex forming sequences in the gapless assembly of human chromosome Y

Dobrovolná,

Mergny,

Brázda

2024

Biochimie

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Y Chromosome Genes May Play Roles in the Development of Neural Rosettes from Human Embryonic Stem Cells

Cited by 4 publications

References 50 publications

Sex-biased gene expression during neural differentiation of human embryonic stem cells

Sex-biased gene expression during neural differentiation of human embryonic stem cells

Genomic insights and advanced machine learning: characterizing autism spectrum disorder biomarkers and genetic interactions

Complete analysis of G-quadruplex forming sequences in the gapless assembly of human chromosome Y

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