Correction to: Single-cell RNA Sequencing Reveals Sexually Dimorphic Transcriptome and Type 2 Diabetes Genes in Mouse Islet β Cells
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PROVIDER: S-EPMC11233144 | biostudies-literature | 2024 Apr
REPOSITORIES: biostudies-literature
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Project description:Sexual size dimorphism is widespread in fish species. Although sex growth differences in multiple species have been studied successively, the commonalities of regulatory mechanisms across sexually dimorphic species are unknown. In this study, we performed RNA-seq analysis of four representative fish (loach, half-smooth tongue sole, yellow catfish, and Nile tilapia) with significant growth differences between females and males. Clean reads were identified from four fish species, ranging from 45,718,052 to 57,733,120. Following comparison transcriptome analysis, there were 1,132 and 1,108, 1,290 and 1,102, 4,732 and 4,266, 748 and 192 differentially expressed genes (DEGs) in the brain and muscle of loach, half-smooth tongue sole, yellow catfish, and Nile tilapia, respectively. Furthermore, the expression levels were validated by quantitative real-time PCR (qRT-PCR). Comparative transcriptome profiles of four fish described here will provide fundamental information for further studies on the commonalities of sexually size dimorphic fish in regulating growth differences between females and males.
| S-EPMC9759545 | biostudies-literature
Project description:Fetal exposure to synthetic glucocorticoids reprograms distinct neural circuits in the developing brain, often in a sex-specific manner, via mechanisms that remain poorly understood. To reveal whether such reprogramming is associated with select molecular signatures, we characterized the transcriptome of primary, embryonic mouse cerebral cortical and hypothalamic neural progenitor/stem cells derived from individual male and female embryos exposed to the synthetic glucocorticoid, dexamethasone. Gene expression profiling by RNA-Seq identified differential expression of common and unique genes based upon brain region, sex, and/or dexamethasone exposure. These gene expression datasets provide a unique resource that will inform future studies examining the molecular mechanisms responsible for region- and sex-specific reprogramming of the fetal brain brought about by in utero exposure to excess glucocorticoids.
| S-EPMC5702594 | biostudies-literature
Project description:The sex-specific prevalence of adrenal diseases has been known for a long time. However, the reason for the high prevalence of these diseases in females is not completely understood. Mouse studies have shown that the adult adrenal gland is sexually dimorphic at different levels such as transcriptome, histology, and cell renewal. Here we used RNA-seq to show that in prepubertal mice, male and female adrenal glands were not only sexually dimorphic but also responded differently to the same external stimulus. We previously reported that thyroid hormone receptor β1 (TRβ1) in the adrenal gland is mainly expressed in the inner cortex and the fate of this TRβ1-expressing cell population can be changed by thyroid hormone (triiodothyronine; T3) treatment. In the present study, we found that adrenal glands in prepubertal mice were sexually dimorphic at the level of the transcriptome. Under T3 treatment, prepubertal females had 1162 genes differentially expressed between the saline and T3 groups, whereas in males of the same age, only 512 genes were T3-responsive. Immunostaining demonstrated that several top sexually dimorphic T3-responsive genes, including Cyp2f2 and Dhcr24, were specifically expressed in the adrenal inner cortex, precisely in an area partially overlapping with the X-zone. Under T3 treatment, a unique cortical layer that surrounds the adrenal X-zone expanded significantly, forming a distinct layer peculiar to females. Our findings identified novel marker genes for the inner adrenal cortex, indicating there are different sub-zones in the zona fasciculata. The results also highlight the sex-specific response to thyroid hormone in the mouse adrenal gland.
| S-EPMC7446775 | biostudies-literature
Project description:Aims/hypothesisType 2 diabetes is characterised by islet amyloid and toxic oligomers of islet amyloid polypeptide (IAPP). We posed the questions, (1) does IAPP toxicity induce an islet response comparable to that in humans with type 2 diabetes, and if so, (2) what are the key transcriptional drivers of this response?MethodsThe islet transcriptome was evaluated in five groups of mice: beta cell specific transgenic for (1) human IAPP, (2) rodent IAPP, (3) human calpastatin, (4) human calpastatin and human IAPP, and (5) wild-type mice. RNA sequencing data was analysed by differential expression analysis and gene co-expression network analysis to establish the islet response to adaptation to an increased beta cell workload of soluble rodent IAPP, the islet response to increased expression of oligomeric human IAPP, and the extent to which the latter was rescued by suppression of calpain hyperactivation by calpastatin. Rank-rank hypergeometric overlap analysis was used to compare the transcriptome of islets from human or rodent IAPP transgenic mice vs humans with prediabetes or type 2 diabetes.ResultsThe islet transcriptomes in humans with prediabetes and type 2 diabetes are remarkably similar. Beta cell overexpression of soluble rodent or oligomer-prone human IAPP induced changes in islet transcriptome present in prediabetes and type 2 diabetes, including decreased expression of genes that confer beta cell identity. Increased expression of human IAPP, but not rodent IAPP, induced islet inflammation present in prediabetes and type 2 diabetes in humans. Key mediators of the injury responses in islets transgenic for human IAPP or those from individuals with type 2 diabetes include STAT3, NF-κB, ESR1 and CTNNB1 by transcription factor analysis and COL3A1, NID1 and ZNF800 by gene regulatory network analysis.Conclusions/interpretationBeta cell injury mediated by IAPP is a plausible mechanism to contribute to islet inflammation and dedifferentiation in type 2 diabetes. Inhibition of IAPP toxicity is a potential therapeutic target in type 2 diabetes.
| S-EPMC8660728 | biostudies-literature
Project description:Sex differences are pervasive in human health and disease. One major key to sex-biased differences lies in the sex chromosomes. Although the functions of the X chromosome proteins are well appreciated, how they compare with their Y chromosome homologs remains elusive. Herein, using ensemble and single-molecule techniques, we report that the sex chromosome-encoded RNA helicases DDX3X and DDX3Y are distinct in their propensities for liquid-liquid phase separation (LLPS), dissolution, and translation repression. We demonstrate that the N-terminal intrinsically disordered region of DDX3Y more strongly promotes LLPS than the corresponding region of DDX3X and that the weaker ATPase activity of DDX3Y, compared with DDX3X, contributes to the slower disassembly dynamics of DDX3Y-positive condensates. Interestingly, DDX3Y-dependent LLPS represses mRNA translation and enhances aggregation of FUS more strongly than DDX3X-dependent LLPS. Our study provides a platform for future comparisons of sex chromosome-encoded protein homologs, providing insights into sex differences in RNA metabolism and human disease.
| S-EPMC9308757 | biostudies-literature
Project description:To further reveal the molecular mechanism underlying sexual differentiation of the mouse cerebral cortex and hippocampus, we reanalyzed our previous microarray study with Gene Ontology (GO) term enrichment and found that the GO term "RNA binding" was over-represented among the 89 sexually dimorphic candidate genes. Thus, we selected 16 autosomal genes annotated to the term RNA binding and profiled their mRNA expression in the developing male and female mouse cortex/hippocampus. During the first three weeks after birth, sex differences in mRNA levels of Khdrbs2, Nanos2, Rbm48, and Tdrd3 were observed in the mouse cortex/hippocampus. Of these genes, only the female-biased expression of Rbm48 in neonates was abolished by prenatal exposure to testosterone propionate (TP), while postnatal treatment of TP three weeks after birth increased Rbm48 and Tdrd3 mRNA levels in both sexes. Regardless of sex, the postnatal cortex/hippocampus also showed a marked increase in the content of androgen receptor (Ar) and estrogen receptor β (Esr2), but a decrease in estrogen receptor α (Esr1) and aromatase (Cyp19a1), which might confer the different responses of Rbm48 to prenatal and postnatal TP. Our results suggest that androgen-regulated, sexually dimorphic Rbm48 expression might present a novel molecular mechanism by which perinatal androgens control development of sexual dimorphism in cortical and hippocampal structure and function.
| S-EPMC6897302 | biostudies-literature
Project description:Background Biological sex is an important modifier of cardiovascular disease and women generally have better outcomes compared with men. However, the contribution of cardiac fibroblasts (CFs) to this sexual dimorphism is relatively unexplored. Methods and Results Isoproterenol (ISO) was administered to rats as a model for chronic β-adrenergic receptor (β-AR)-mediated cardiovascular disease. ISO-treated males had higher mortality than females and also developed fibrosis whereas females did not. Gonadectomy did not abrogate this sex difference. To determine the cellular contribution to this phenotype, CFs were studied. CFs from both sexes had increased proliferation in vivo in response to ISO, but CFs from female hearts proliferated more than male cells. In addition, male CFs were significantly more activated to myofibroblasts by ISO. To investigate potential regulatory mechanisms for the sexually dimorphic fibrotic response, β-AR mRNA and PKA (protein kinase A) activity were measured. In response to ISO treatment, male CFs increased expression of β1- and β2-ARs, whereas expression of both receptors decreased in female CFs. Moreover, ISO-treated male CFs had higher PKA activity relative to vehicle controls, whereas ISO did not activate PKA in female CFs. Conclusions Chronic in vivo β-AR stimulation causes fibrosis in male but not female rat hearts. Male CFs are more activated than female CFs, consistent with elevated fibrosis in male rat hearts and may be caused by higher β-AR expression and PKA activation in male CFs. Taken together, our data suggest that CFs play a substantial role in mediating sex differences observed after cardiac injury.
| S-EPMC8483546 | biostudies-literature
Project description:Germ cells specified during fetal development form the foundation of the mammalian germline. These primordial germ cells (PGCs) undergo rapid proliferation, yet the germline is highly refractory to mutation accumulation compared with somatic cells. Importantly, while the presence of endogenous or exogenous DNA damage has the potential to impact PGCs, there is little known about how these cells respond to stressors. To better understand the DNA damage response (DDR) in these cells, we exposed pregnant mice to ionizing radiation (IR) at specific gestational time points and assessed the DDR in PGCs. Our results show that PGCs prior to sex determination lack a G1 cell cycle checkpoint. Additionally, the response to IR-induced DNA damage differs between female and male PGCs post-sex determination. IR of female PGCs caused uncoupling of germ cell differentiation and meiotic initiation, while male PGCs exhibited repression of piRNA metabolism and transposon derepression. We also used whole-genome single-cell DNA sequencing to reveal that genetic rescue of DNA repair-deficient germ cells (Fancm-/- ) leads to increased mutation incidence and biases. Importantly, our work uncovers novel insights into how PGCs exposed to DNA damage can become developmentally defective, leaving only those genetically fit cells to establish the adult germline.
| S-EPMC7706705 | biostudies-literature
Project description:Bipolar disorders are heritable psychiatric conditions often abstracted by separate animal models for mania and depression. The principal mania models involve transgenic manipulations or treatment with stimulants. An additional approach involves analysis of naturally occurring mania models including an inbred strain our lab has recently characterized, the Madison (MSN) mouse strain. These mice show a suite of behavioral and neural genetic alterations analogous to manic aspects of bipolar disorders. In the current study, we extended the MSN strain's behavioral phenotype in new directions by examining in-cage locomotor activity. We found that MSN activity presentation is sexually dimorphic, with MSN females showing higher in-cage activity than MSN males. When investigating development, we found that MSN mice display stable locomotor hyperactivity already observable when first assayed at 28 days postnatal. Using continuous monitoring and analysis for 1 month, we did not find evidence of spontaneous bipolarism in MSN mice. However, we did find that the MSN strain displayed an altered diurnal activity profile, getting up earlier and going to sleep earlier than control mice. Long photoperiods were associated with increased in-cage activity in MSN, but not in the control strain. The results of these experiments reinforce the face validity of the MSN strain as a complex mania model, adding sexual dimorphism, an altered diurnal activity profile, and seasonality to the suite of interesting dispositional phenomena related to mania seen in MSN mice.
| S-EPMC3742520 | biostudies-literature
Project description:The cerebral cortex and hippocampus are important for the control of cognitive functions and social behaviors, many of which are sexually dimorphic and tightly regulated by gonadal steroid hormones via activation of their respective nuclear receptors. As different levels of sex steroid hormones are present between the sexes during early development and their receptors act as transcription factors to regulate gene expression, we hypothesize that sexually dimorphic gene expression in the developing mouse cortex and hippocampus might result in sex differences in brain structures and neural circuits governing distinct behaviors between the sexes as adults. To test our hypothesis, we used gene expression microarrays to identify 90 candidate genes differentially expressed in the neonatal cortex/hippocampus between male and female mice, including 55 male-biased and 35 female-biased genes. Among these genes, sexually dimorphic expression of eight sex chromosome genes was confirmed by reverse transcription with quantitative PCR (RT-qPCR), including three located on the X chromosome (Xist, Eif2s3x, and Kdm6a), three on the Y chromosome (Ddx3y, Eif2s3y, and Kdm5d), and two in the pseudoautosomal region of the X and Y chromosomes (Erdr1 and Mid1). In addition, five autosomal genes (Cd151, Dab2, Klk8, Meg3, and Prkdc) were also validated for their sexually dimorphic expression in the neonatal mouse cortex/hippocampus. Gene Ontology annotation analysis suggests that many of these sexually dimorphic genes are involved in histone modifications, cell proliferation/death, androgen/estrogen signaling pathways, and synaptic organization, and these biological processes have been implicated in differential neural development, cognitive function, and neurological diseases between the sexes.
| S-EPMC4058436 | biostudies-literature