Expression Patterns Research Articles

Abstract C087: Distinct gene expression and DNA methylation pattern associated with poor outcome of B-cell acute lymphoblastic leukemia in Hispanic/Latino children

Abstract C087: Distinct gene expression and DNA methylation pattern associated with poor outcome of B-cell acute lymphoblastic leukemia in Hispanic/Latino children

Abstract C097: PVT1 exon 9-dependent overexpression of RSAD2 is a characteristic of prostate cancer in males of African ancestry

Abstract Aggressive prostate cancer (PCa), including castrate-resistant and neuroendocrine subtypes, is projected to increase in incidence 5% each year. Aggressive PCa disproportionally impacts African American men, has limited effective treatment options and high mortality rates. Although racial disparities are established in PCa development, attributed to multiple contributory factors including systemic racism, differences in socioeconomic status and distrust in the medical system, work is still needed to understand the contribution of biological factors. We found the exon 9 region of plasmacytoma variant translocation 1 (PVT1) overexpressed in aggressive PCa cell lines derived from African American (AA) men. We found PVT1 exon 9 overexpression induced phenotypic changes to normal prostate epithelial cells in vitro and led to tumor formation in vivo. RNA-sequencing analysis revealed 156 significantly differentially expressed genes influenced by PVT1 exon 9 overexpression and radical S-adenosyl methionine domain containing 2 (RSAD2) was the top significantly overexpressed gene (log2Fold change 1.71, p-value < 0.05). We utilized the GSE223405 publicly available dataset to identify whether our identified PVT1 exon 9 downstream genes were enriched in AA prostate cancer cells. RSAD2 was significantly overexpressed in AA prostate cancer cells compared to prostate cancer cells from men of European ancestry (moEA) (log2Fold change 6.18, p-value < 0.05). Comparing normal cells to prostate cancer cells between these groups, we found that normal AA prostate cells had significantly higher expression of RSAD2 (log2fold change 4.25, p-value < 0.001) whereas moEA samples did not (log2fold change 0.837, p-value=0.150). From analysis of data obtained from cBioPortal, we found RSAD2 alteration significantly correlates (p-value < 0.001) with self-identified race and copy number overexpression of RSAD2 was found to be enriched in AA patients (18.16% moEA versus 24% AA). Finally, we found 88.6% of the significantly differentially expressed genes within our PVT1 exon 9 RNA-sequencing dataset were significantly differentially expressed in GSE223405 AA samples and of those, 51.7% of genes exhibited a similar differential expression pattern suggesting that the PVT1 exon 9/RSAD2 dependent pathway may be more prominent in AA men. Mechanistically, we found two differing pathways of RSAD2 overexpression in aggressive prostate cancer cell models, one dependent and one independent of PVT1 exon 9 overexpression, with similar but differing biological functions related to epigenetic processes and metabolism. Ongoing work is investigating the RSAD2 and PVT1 exon 9 expression axis in a diverse set of human prostate cancer tissues and investigating their utilization as a therapeutic target in prostate cancer. Citation Format: Rachel E. Sexton-Bonacci1, Murtaza Barkarar1, Chindeum Udekwu1, Olorunseun O. Ogunwobi1. PVT1 exon 9-dependent overexpression of RSAD2 is a characteristic of prostate cancer in males of African ancestry [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr C097.

Abstract C101: Shared gene expression pattern among breast cancer subtypes and its association with prognostic variables in Colombian patients

Abstract C101: Shared gene expression pattern among breast cancer subtypes and its association with prognostic variables in Colombian patients

Involvement of extracellular vesicle microRNA clusters in developing healthy and Rett syndrome brain organoids

Rett syndrome (RTT) is a neurodevelopmental disorder caused by de novo mutations in the MECP2 gene. Although miRNAs in extracellular vesicles (EVs) have been suggested to play an essential role in several neurological conditions, no prior study has utilized brain organoids to profile EV-derived miRNAs during normal and RTT-affected neuronal development. Here we report the spatiotemporal expression pattern of EV-derived miRNAs in region-specific forebrain organoids generated from female hiPSCs with a MeCP2:R255X mutation and the corresponding isogenic control. EV miRNA and protein expression profiles were characterized at day 0, day 13, day 40, and day 75. Several members of the hsa-miR-302/367 cluster were identified as having a time-dependent expression profile with RTT-specific alterations at the latest developmental stage. Moreover, the miRNA species of the chromosome 14 miRNA cluster (C14MC) exhibited strong upregulation in RTT forebrain organoids irrespective of their spatiotemporal location. Together, our results suggest essential roles of the C14MC and hsa-miR-302/367 clusters in EVs during normal and RTT-associated neurodevelopment, displaying promising prospects as biomarkers for monitoring RTT progression.Graphical

Transcriptomic analysis reveals differential gene expression patterns during cannabis leaf morphogenesis and phase transition

ABSTRACT Understanding the molecular mechanisms governing leaf morphogenesis and phase transition in Cannabis sativa is critical for optimizing its growth, development and yield. In this study, we conducted a comparative transcriptomic analysis to investigate the gene expression patterns associated with leaf development and the transition from vegetative to reproductive phases in cannabis plants. Following germination, cannabis plants display a distinct leaf developmental pattern. While the specific number of leaflets varies among cultivars, here we focused on the White Widow cultivar as a model. It showed an increase in the number of serrated leaflets from one (L1) to nine (L5) in a node-specific manner. Subsequently, the number of leaflets decreased from eight (L6) to three (L9). The transition from vegetative to reproductive phases, marked by the appearance of solitary flowers and a shift from opposite to alternate leaf phyllotaxy, occurred at node 7 and node 12, respectively. Analysis of gene expression revealed 1358 differentially expressed genes, with 1,182 genes showing differential expression across all leaves. Notably, several genes involved in leaf morphogenesis (e.g. YAB, AGO5, and TCP4) were found to be upregulated in compound leaves (L2) compared to simple leaves (L1), implying a role in leaflet formation and overall leaf morphology. Furthermore, several genes associated with phase transition and flowering (e.g. SPLs, ELFs, SOC1, and CEN-Like) exhibited specific expression patterns during the transition from vegetative to reproductive phases. These findings provide valuable insights into the genetic regulation of leaf morphogenesis and phase transition in cannabis.

Circadian cilia transcriptome in mouse brain across physiological and pathological states

Primary cilia are dynamic sensory organelles that continuously undergo structural modifications in response to environmental and cellular signals, many of which exhibit rhythmic patterns. Building on our previous findings of rhythmic cilia-related gene expression in diurnal primates (baboon), this study extends the investigation to the nocturnal mouse brain to identify circadian patterns of cilia gene expression across brain regions. We used computational techniques and transcriptomic data from four publicly available databases, to examine the circadian expression of cilia-associated genes within six brain areas: brainstem, cerebellum, hippocampus, hypothalamus, striatum, and suprachiasmatic nucleus. Our analysis reveals that a substantial proportion of cilia transcripts exhibit circadian rhythmicity across the examined regions, with notable overrepresentation in the striatum, hippocampus, and cerebellum. We also demonstrate region-specific variations in the abundance and timing of circadian cilia genes’ peaks, indicating an adaptation to the distinct physiological roles of each brain region. Additionally, we show that the rhythmic patterns of cilia transcripts are shifted under various physiological and pathological conditions, including modulation of the dopamine system, high-fat diet, and epileptic conditions, indicating the adaptable nature of cilia transcripts’ oscillation. While limited to a few mouse brain regions, our study provides initial insights into the distinct circadian patterns of cilia transcripts and highlights the need for future research to expand the mapping across wider brain areas to fully understand the role of cilia’s spatiotemporal dynamics in brain functions.

Identification of Reference Gene for Quantitative Gene Expression in Early-Term and Late-Term Cultured Canine Fibroblasts Derived from Ear Skin

Fibroblasts are cells that reside within the fibrous or loose connective tissues of most mammalian organs. For research purposes, fibroblasts are often subjected to long-term culture under defined conditions, during which their properties can significantly change. It is essential to understand and document these changes to obtain reliable outcomes. For the quantification of specific gene expressions, the most reliable and widely used technique is quantitative real-time polymerase chain reaction (qRT-PCR). Here, we assessed the impact of a reference gene’s stability on a qRT-PCR analysis of long-term cultured canine skin fibroblasts. After successfully isolating the fibroblasts from canine skin tissues, they were cultured and evaluated for proliferation and β-galactosidase activity at different passage numbers. With extended culture, the fibroblasts showed a long doubling time and elevated β-galactosidase activity. Using three widely used algorithms, geNorm, Normfinder, and Bestkeeper, we identified HPRT1, YWHAZ, and GUSB as the most stable reference genes for both early- and late-passage fibroblasts. Conventional reference genes such as GAPDH were found to be less stable than those genes. The normalization of Vimentin by the stable genes showed statistical differences, whereas normalization by an unstable gene did not. Collectively, this study indicates that using stable reference genes is essential for accurately and reliably measuring gene expression in both early- and late-passage fibroblasts. These findings provide valuable insights into internal controls for gene expression studies and are expected to be utilized for analyzing gene expression patterns in molecular biology research.

Characterization and Gene Expression Patterns of Calpain Family in Striped Catfish

Characterization and Gene Expression Patterns of Calpain Family in Striped Catfish

Identification of WRKY transcription factors in Rosa chinensis and analysis of their expression response to alkali stress response

Breeding abiotic stress-tolerant varieties of Rosa chinensis is a paramount goal in horticulture. WRKY transcription factors, pivotal in plant responses to diverse stressors, offer potential targets for enhancing stress resilience in R. chinensis. Using bioinformatics and genomic data, we identified RcWRKY transcription factor genes, characterised their chromosomal distribution, phylogenetic relationships, structural attributes, collinearity, and expression patterns in response to saline stress. Leveraging bidirectional database searches, we pinpointed 66 RcWRKY genes, categorised into three groups. All except RcWRKY60 encoded DNA Binding Domain and Zinc Finger Motif regions of the WRKY domain. Expansion of the RcWRKY gene family was propelled by 19 segmental, and 2 tandem, duplications. We unveiled 41 and 15 RcWRKY genes corresponding to 50 AtWRKY and 17 OsWRKY orthologs respectively, indicating postdivergence expansion. Expression analyses under alkaline stress pinpointed significant alterations in 54 RcWRKY genes. Integration of functional roles from their Arabidopsis orthologs and cis-acting elements within their promoters, along with quantitative reverse transcription PCR validation, underscored the importance of RcWRKY27 and 29 in R. chinensis’ alkaline stress response. These findings offer insights into the biological roles of RcWRKY transcription factors, as well as the regulatory dynamics governing R. chinensis’ growth, development, and stress resilience.

Expression patterns of housekeeping genes and tissue-specific genes in black goats across multiple tissues

Black goats are a significant meat breed in southern China. To investigate the expression patterns and biological functions of genes in various tissues of black goats, we analyzed housekeeping genes (HKGs), tissue-specific genes (TSGs), and hub genes (HUBGs) across 23 tissues. Additionally, we analyzed HKGs in 13 tissues under different feeding conditions. We identified 2968 HKGs, including six important ones. Interestingly, HKGs in grazing black goats demonstrated higher and more stable expression levels. We discovered a total of 9912 TSGs, including 134 newly identified ones. The number of TSGs for mRNA and lncRNA were nearly equal, with 127 mRNA TSGs expressed solely in one tissue. Additionally, the predicted functions of tissue-specific long non-coding RNAs (lncRNAs) targeting mRNAs corresponded with the physiological functions of the tissues.Weighted gene co-expression network analysis (WGCNA) constructed 30 modules, where the dark grey module consists almost entirely of HKGs, and TSGs are located in modules most correlated with their respective tissues. Additionally, we identified 289 HUBGs, which are involved in regulating the physiological functions of their respective tissues. Overall, these identified HKGs, TSGs, and HUBGs provide a foundation for studying the molecular mechanisms affecting the genetic and biological processes of complex traits in black goats.

An in vitro assessment of ionizing radiation impact on the efficacy of radiotherapy for breast cancer

Abstract Objectives Ionizing radiation is still one of the most effective treatment options for various cancers. It is possible to reduce the side effects of this effective treatment method and increase the chance of success by elucidating the responses it creates at the molecular level in the cell. This study aims to investigate of the molecular effects of therapeutic ionizing radiation on breast cancer, which is the most prevalent cancer type. Methods MDA-MB-231 and MCF7 cell lines were irradiated with 4 and 8 Gy ionizing radiation and monitored for up to 7 days. RNA was collected at 48 and 96 h, when cellular molecular mechanisms became most evident, and quantitative expression levels of microRNAs (miR-208a, miR-124, miR-145), for which cancer-radiation associations have been determined from existing literature and databases, were evaluated. Results Exposure to ionizing radiation resulted in a dose-dependent reduction in cell viability in both MCF7 and MDA-MB-231 breast cancer cell lines. Furthermore, microRNA expression analysis revealed notable changes at all levels. The research demonstrates that miR-208a, miR-145, and miR-124 are crucial in the biological response to ionizing radiation. Conclusions Therapeutic ionizing radiation profoundly affects cell viability and microRNA expression in breast cancer cell lines, showing dose and time-dependent effects. The observed microRNA expression patterns suggest potential biomarkers for radiation response and therapeutic targets to improve radiotherapy efficacy. Further in vivo validation and exploration of these microRNAs’ roles in modulating cellular response to ionizing radiation are needed.

Extracellular RNAs from Whole Urine to Distinguish Prostate Cancer from Benign Prostatic Hyperplasia

RNAs, especially non-coding RNAs (ncRNAs), are crucial players in regulating cellular mechanisms due to their ability to interact with and regulate other molecules. Altered expression patterns of ncRNAs have been observed in prostate cancer (PCa), contributing to the disease’s initiation, progression, and treatment response. This study aimed to evaluate the ability of a specific set of RNAs, including long ncRNAs (lncRNAs), microRNAs (miRNAs), and mRNAs, to discriminate between PCa and the non-neoplastic condition benign prostatic hyperplasia (BPH). After selecting by literature mining the most relevant RNAs differentially expressed in biofluids from PCa patients, we evaluated their discriminatory power in samples of unfiltered urine from 50 PCa and 50 BPH patients using both real-time PCR and droplet digital PCR (ddPCR). Additionally, we also optimized a protocol for urine sample manipulation and RNA extraction. This two-way validation study allowed us to establish that miRNAs (i.e., miR-27b-3p, miR-574-3p, miR-30a-5p, and miR-125b-5p) are more efficient biomarkers for PCa compared to long RNAs (mRNAs and lncRNAs) (e.g., PCA3, PCAT18, and KLK3), as their dysregulation was consistently reported in the whole urine of patients with PCa compared to those with BPH in a statistically significant manner regardless of the quantification methodology performed. Moreover, a significant increase in diagnostic performance was observed when molecular signatures composed of different miRNAs were considered. Hence, the abovementioned circulating ncRNAs represent excellent potential non-invasive biomarkers in urine capable of effectively distinguishing individuals with PCa from those with BPH, potentially reducing cancer overdiagnosis.

Deciphering the role of claudins in lung cancer

Lung cancer remains a major global health challenge, characterized by aggressive malignancy and poor prognostic outcomes. This review article focuses on the pivotal role of claudins, a family of tight junction proteins, in the pathophysiology of lung cancer. Claudins are integral to maintaining epithelial barrier function and cellular polarity, yet they are intricately involved in the progression and metastasis of lung cancer. The aberrant expression of claudins has been observed across various histological subtypes of lung cancer, indicating their potential as diagnostic and prognostic biomarkers. Specifically, claudins such as claudin-1, -2, -3, -4, and -7 exhibit diverse expression patterns that correlate with tumor aggressiveness, patient survival rates, and response to therapies. Inflammation and cytokine modulation significantly influence claudin expression, affecting tumor microenvironment dynamics and cancer progression. This review also highlights the therapeutic implications of targeting claudins, particularly in cases resistant to conventional treatments. Recent advances in this area suggest that claudin-modulating agents may enhance the efficacy of existing therapies and offer new avenues for targeted interventions. By integrating the latest research, this article aims to provide a comprehensive understanding of claudin’s roles in lung cancer and encourages further clinical trials to explore claudin-targeting therapies. This could pave the way for more effective management strategies, improving outcomes for lung cancer patients.

Expression pattern of the fused in sarcoma gene and its contextual influence on the density-specific response of the growth hormone/insulin-like growth factor 1 axis in zig-zag eels (Mastacembelus armatus)

The fused in sarcoma (FUS) protein is a DNA/RNA binding protein from the ten-eleven translocation protein family that is associated with neurodegeneration, and it has been shown to promote cell proliferation through the growth hormone/insulin-like growth factor 1 (Gh/Igf-1) signaling pathway. The zig-zag eel (Mastacembelus armatus) is a newly discovered species exhibiting sexual dimorphism in growth, and the potential role of fus in the growth and development of this species remains largely unknown. Herein, we analyzed the homology, conserved domains, evolutionary characteristics, and conserved syntenies of fus in several teleost species. The expression of fus was predominant in the brain and exhibited sexual dimorphism in the brain, muscle, and liver of zig-zag eels. We found that microRNA (miR)-146-5p, miR-489-3p, and 24 other miRNAs were targeted to the fus 3′ untranslated region, which might affect muscle and bone development in adults. The igf1, insulin-like growth factor 1 receptor a (igf1ra), insulin-like growth factor 2 receptor (igf2r), growth hormone-releasing hormone-like receptor (ghrhrl), growth hormone secretagogue receptor type 1 (ghsr), and glucocorticoid receptor (gr) genes contained a higher abundance of GU-rich fus motifs compared to the other four genes analyzed in zig-zag eels. We also measured the expression of fus mRNA during fish culture at various stocking densities to further elucidate the relationship between fus expression and the Gh/Igf-1 axis. After 100 days of fish cultivation, the expression of fus and ghrhrl decreased and the expression of ghrh and gr increased as the culture density increased (p < 0.05). The expression of fus exhibited a remarkable positive correlation with a specific growth rate. These results indicate that fus mediates growth differences by regulating the expression of several growth-related genes including Gh/Igf-1 axis genes in zig-zag eels.

Transcriptional Patterns in Stages of Alzheimer's Disease are Cell Type Specific and Partially Converge with the Effects of Alcohol Use Disorder in Humans

Advances in single cell technologies have led to the discovery and characterization of new brain cell-types, that in turn lead to a better understanding of the pathogenesis of Alzheimer’s disease (AD). Here, we present a detailed analysis of single nucleus (sn)RNA-seq data for three stages of AD from middle temporal gyrus (MTG) and compare it with snRNA-seq data from the prefrontal cortices from individuals with alcohol use disorder (AUD). We observed a significant decrease in both inhibitory and excitatory neurons, in general agreement with previous reports. We observed several cell-type specific gene expressions and pathways dysregulations that delineate AD stages. Endothelial and VLMCs (vascular leptomeningeal cells) showed the greatest degree of gene expression changes. Cell-type specific evidence of neurodegeneration was seen in multiple neuronal cell-types particularly in SST (somatostatin) and L5 ET (layer-5 extra-telencephalic) neurons, among others. Evidence of inflammatory responses were seen in non-neuronal cells, particularly in intermediate and advanced AD. We observed common perturbations in AD and AUD, particularly in pathways, like transcription, translation, apoptosis, autophagy, calcium signaling, neuroinflammation, and phosphorylation, that imply shared transcriptional pathogenic mechanisms and support a role for excessive alcohol intake in AD progression. Major AUD gene markers form and perturb a network of genes significantly associated with intermediate and advanced AD. Master regulator analysis from AUD gene markers revealed significant correlation with advanced AD of transcription factors that have implications in intellectual disability, neuroinflammation, and other neurodegenerative conditions, further suggesting a shared nexus of transcriptional changes between AD and AUD.Significance StatementThis study holds significant implications for understanding the intricate molecular landscape of Alzheimer's disease (AD) and its intersection with alcohol use disorder (AUD). By profiling transcriptional changes in the neocortex associated with AD progression and comparing them with those in AUD, we shed light on shared gene expression and pathway dysregulations between the two conditions. Our findings corroborate prior research on neuronal depletion and highlight novel insights into cell-type-specific gene expression patterns in AD stages. Moreover, the identification of common genetic signatures suggests a potential exacerbating effect of AUD on AD progression. This comprehensive analysis not only deepens our understanding of AD pathology but also underscores the importance of considering AUD as a potential risk factor for accelerating AD onset or severity.

Abiotic Stress in Cotton: Insights into Plant Responses and Biotechnological Solutions

Climate change has rapidly increased incidences of frequent extreme abiotic stresses, such as heat, drought, salinity, and waterlogging. Each of these stressors negatively affects the cotton crop (Gossypium spp.) and results in significant yield decreases. Every stressful event causes specific changes in the metabolism and physiology of plants, which are linked to complex molecular alterations. Understanding the molecular mechanisms that regulate a plant’s response to stress is essential to developing stress-resistant cotton varieties that can withstand various stress factors. Gene expressions in response to multiple stresses have been studied and mapped. These genes include ion transporters and heat shock proteins, which are vital to allowing adaptive responses. These approaches showed the ability to employ advanced genome sequencing and multi-omics techniques to identify dynamic gene expression patterns and elucidate intricate regulatory networks. Using genetic variation in combination with molecular techniques, it would be possible to generate stress-resilient cotton varieties that would enable sustainable cotton output in the face of abiotic stresses. Here, we reviewed the effects of major abiotic stressors on cotton plants, such as heat, salinity, drought, heavy metals, and waterlogging. We also examine the vast network of proteins, genes, and stress-sensitive signaling pathways that help cotton tolerate abiotic stress.

Characterization and Transcriptomic Analysis of Sorghum EIN/EIL Family and Identification of Their Roles in Internode Maturation

Ethylene-insensitive 3/Ethylene-insensitive3-like proteins (EIN3/EIL) represent a group of transcription factors critical for the ethylene signaling transduction that manipulate downstream ethylene-responsive genes, thereby regulating plant growth, development, and stress responses. However, the identification, evolution, and divergence of the EIL family remain to be studied in Sorghum bicolor. Here, we identified eight SbEILs, which were expanded due to whole-genome-duplication (WGD) events. Characterization of the protein sequences and expression atlas demonstrates that the WGD-duplicated SbEILs could become divergent due to the differential expression patterns, rather than domain and motif architectures. Comparative expression analysis was performed between the RNA-seq data sets of internodes from several sorghum cultivars to understand the potential roles of SbEIL members in internode elongation and maturation. Our results identified SbEIL3 and 7 (the latter as a homolog of OsEIL7/OsEIL1) to be the highly expressed SbEIL genes in sorghum internodes and revealed a potential functional link between SbEIL7 and internode maturation. The co-expression analysis and comparative expression analysis with ethylene-regulated gene sets found that SbEIL7 was co-regulated with a set of ubiquitin-related protein degradation genes, suggesting possible involvement of SbEIL7 in protein degradation and processing during the post-anthesis stages. Altogether, our findings lay a foundation for future functional studies of ethylene signaling-mediated gene regulation and improvement of sorghum internode development.

LncRNA HOTAIR and Cardiovascular diseases.

Cardiovascular diseases (CVDs) a major contributor to global mortality rates, with a steadily rising prevalence observed across the world. Understanding the molecular mechanisms that underlie the signaling pathways implicated in the pathogenesis of CVDs represents a salient and advantageous avenue toward the development of precision and targeted therapeutics. A recent development in CVDs research is the discovery of long non-coding RNAs (lncRNAs), which are now understood to have crucial roles in the onset and development of several pathophysiological processes. The distinct expression patterns exhibited by lncRNAs in various CVDs contexts, present a significant opportunity for their utilization as both biomarkers and targets for therapeutic intervention. Among the various identified lncRNAs, HOX antisense intergenic RNA (HOTAIR) functions as signaling molecules that are significantly implicated in the pathogenesis of cardiovascular disorders in response to risk factors. HOTAIR has been observed to circulate within the bloodstream and possesses an integral epigenetic regulatory function in the transcriptional pathways of many diseases. Recent studies have suggested that HOTAIR offers promise as a biomarker for the detection and treatment of CVDs. The investigation on HOTAIR's role in CVDs, however, is still in its early phases. The goal of the current study is to give a thorough overview of recent developments in the field of analyzing the molecular mechanism of HOTAIR in controlling the pathophysiological processes of CVDs as well as its possible therapeutic uses.

The Transcriptome Characterization of the Hypothalamus and the Identification of Key Genes during Sexual Maturation in Goats

Sexual maturation in goats is a dynamic process regulated precisely by the hypothalamic–pituitary–gonadal axis and is essential for reproduction. The hypothalamus plays a crucial role in this process and is the control center of the reproductive activity. It is significant to study the molecular mechanisms in the hypothalamus regulating sexual maturation in goats. We analyzed the serum hormone profiles and hypothalamic mRNA expression profiles of female goats during sexual development (1 day old (neonatal, D1, n = 5), 2 months old (prepuberty, M2, n = 5), 4 months old (sexual maturity, M4, n = 5), and 6 months old (breeding period, M6, n = 5)). The results indicated that from D1 to M6, serum hormone levels, including FSH, LH, progesterone, estradiol, IGF1, and leptin, exhibited an initial increase followed by a decline, peaking at M4. Furthermore, we identified a total of 508 differentially expressed genes in the hypothalamus, with a total of four distinct expression patterns. Nuclear receptor subfamily 1, group D, member 1 (NR1D1), glucagon-like peptide 1 receptor (GLP1R), and gonadotropin-releasing hormone 1 (GnRH-1) may contribute to hormone secretion, energy metabolism, and signal transduction during goat sexual maturation via circadian rhythm regulation, ECM receptor interactions, neuroactive ligand–receptor interactions, and Wnt signaling pathways. This investigation offers novel insights into the molecular mechanisms governing the hypothalamic regulation of goat sexual maturation.

Transcriptomic correlates of state modulation in GABAergic interneurons: A cross-species analysis

GABAergic inhibitory interneurons comprise many subtypes that differ in their molecular, anatomical and functional properties. In mouse visual cortex, they also differ in their modulation with an animal’s behavioural state, and this state modulation can be predicted from the first principal component (PC) of the gene expression matrix. Here, we ask whether this link between transcriptome and state-dependent processing generalises across species. To this end, we analysed seven single-cell and single-nucleus RNA sequencing datasets from mouse, human, songbird, and turtle forebrains. Despite homology at the level of cell types, we found clear differences between transcriptomic PCs, with greater dissimilarities between evolutionarily distant species. These dissim­ilarities arise from two factors: divergence in gene expression within homologous cell types and divergence in cell type abundance. We also compare the expression of cholinergic receptors, which are thought to causally link transcriptome and state modulation. Several cholinergic receptors predictive of state modulation in mouse interneurons are differentially expressed between species. Circuit modelling and mathematical analyses suggest conditions under which these expression differences could translate into functional differences.Significance StatementThe brain is a complex network of many different cell types. A particularly diverse group of cells is that of inhibitory interneurons, named for their suppressive effect. These interneurons change their activity depending on an animal’s behavioural state—at least in mice. Here, we investigate if this finding generalises to other species by comparing gene expression patterns of human, turtle, and zebra finch interneurons. Despite sharing an evolutionary past, we find that only human and mouse interneurons have similar gene expression patterns associated with state modulation. A mathematical model suggests which expression differences in individual cells translate into functional differences at the network level.