Biology subjects

Jiang, J.

Publications and source records attributed to Jiang, J..

At least 181 records · Page 10Linked to original sources

bioRxiv2023

Castration Model Illuminates Sex Differences in Healthy Aging: Insights from Metabolome and Transcriptome Analyses

BackgroundSex, as a critical biological variable, has historically been underappreciated, despite the pervasive influence of sexual dimorphism across physiological and pathological processes. A significant obstacle to advancing sex-biased biological research is the absence of an effective animal model. In recent years, castration has emerged as a potential model for elucidating sex-based differences in the context of healthy aging, where it has been shown to equalize lifespan and growth trajectories in genetically diverse mice. However, the molecular shifts induced by castration in common laboratory models, such as C57BL/6 mice, and the broader applicability of this model to other sex-related biological contexts remain largely unexplored. MethodsWe employed multi-omics and observational analyses to investigate the molecular changes associated with sex and sex hormones following castration. We analyzed serum, kidney, and liver samples from 12-week-old and 18-month-old castrated male C57BL/6 mice, alongside intact male and female counterparts. The castration model was further applied to assess differences in cisplatin-induced toxicity and age-related cognitive decline in comparison to unaltered controls. ResultsLC-MS/MS metabolomics revealed that castrated males exhibited substantial alterations in steroid hormone levels and increased concentrations of antioxidant compounds, such as taurine, despite identical diets. Integrated metabolome-transcriptome analysis confirmed distinct patterns of lipid peroxidation and oxidative stress across sham-operated female, male, and castrated male mice. Histopathological evaluations following cisplatin treatment and aging-related behavioral tests demonstrated the models utility in investigating sex-dependent drug toxicity and cognitive decline. These findings underscored the critical role of sex hormones in modulating both toxicity defense mechanisms and cognitive performance. ConclusionThis study provides a systematic multi-omics spectrum on the castration model and demonstrates its capacity to feminize metabolic and transcriptomic profiles, establishing it as a valuable tool for exploring sex hormone-driven biological differences. Our findings lay the groundwork for further mechanistic studies and broaden the potential applications of the castration model in diverse biomedical research domains.

systems biology↗

bioRxiv2023

Highly multiplexed, image-based pooled screens in primary cells and tissues with PerturbView

Optical pooled screening (OPS) is a highly scalable method for linking image-based phenotypes with cellular perturbations. However, it has thus far been restricted to relatively low-plex phenotypic readouts in cancer cell lines in culture, due to limitations associated with in situ sequencing (ISS) of perturbation barcodes. Here, we developed PerturbView, an OPS technology that leverages in vitro transcription (IVT) to amplify barcodes prior to ISS, enabling screens with highly multiplexed phenotypic readouts across diverse systems, including primary cells and tissues. We demonstrate PerturbView in iPSC-derived neurons, primary immune cells, and tumor tissue sections from animal models. In a screen of immune signaling pathways in primary bone marrow-derived macrophages, PerturbView uncovered both known and novel regulators of NF{kappa}B signaling. Furthermore, we combined PerturbView with spatial transcriptomics in tissue sections from a mouse xenograft model, paving the way to in vivo screens with rich optical and transcriptomic phenotypes. PerturbView broadens the scope of OPS to a wide range of models and applications.

systems biology↗

bioRxiv2023

Scm6A: A fast and low-cost method for quantifying m6A modifications at the single-cell level

It is widely accepted that m6A exhibits significant intercellular specificity, which poses challenges for its detection using existing m6A quantitative methods. In this study, we introduce Scm6A, a machine learning-based approach for single-cell m6A quantification. Scm6A leverages input features derived from the expression levels of m6A trans regulators and cis sequence features, and found that Scm6A offers remarkable prediction efficiency and reliability. To further validate the robustness and precision of Scm6A, we applied a winscore-based m6A calculation method to conduct m6A-seq analysis on CD4+ and CD8+ T-cells isolated through magnetic-activated cell sorting (MACS). Subsequently, we employed Scm6A for analysis on the same samples. Notably, the m6A levels calculated by Scm6A exhibited a significant positive correlation with m6A quantified through m6A-seq in different cells isolated by MACS, providing compelling evidence for Scm6As reliability. We also used the scm6A-seq method to validate the reliability of our approach. Additionally, we performed single-cell level m6A analysis on lung cancer tissues as well as blood samples from COVID-19 patients, and demonstrated the landscape and regulatory mechanisms of m6A in different T-cell subtypes from these diseases. In summary, our work has yielded a novel, dependable, and accurate method for single-cell m6A detection. We are confident that Scm6A will have broad applications in the realm of m6A-related research.

bioinformatics↗

bioRxiv2023

Temporal dynamics and representational consequences of the control of processing conflict between visual working memory and visual perception

Visual working memory (WM) extensively interacts with visual perception. When information between the two processes is in conflict, cognitive control can be recruited to effectively mitigate the resultant interference. The current study investigated the neural bases of the control of conflict between visual WM and visual perception. We recorded the electroencephalogram (EEG) from 25 human subjects (13 male) performing a dual task combining visual WM and tilt discrimination, the latter occurring during the WM delay. The congruity in orientation between the memorandum and the discriminandum was manipulated. Behavioral data were fitted to a reinforcement-learning model of cognitive control to derive trial-wise estimates of demand for proactive and reactive control, which were then used for EEG analyses. The level of proactive control was associated with sustained frontal-midline theta activity preceding trial onset, as well as with the strength of the neural representation of the memorandum. Subsequently, discriminandum onset triggered a control prediction error signal that was reflected in a left frontal positivity. On trials when an incongruent discriminandum was not expected, reactive control that scaled with the prediction error acted to suppress the neural representation of the discriminandum, producing below-baseline decoding of the discriminandum that, in turn, exerted a repulsive serial bias on WM recall on the subsequent trial. These results illustrate the flexible recruitment of two modes of control and how their dynamic interplay acts to mitigate interference between simultaneously processed perceptual and mnemonic representations. Significance StatementOne hallmark of human cognition is the context dependent, flexible control of behavior. Here we studied the "mental juggling" required when, while holding information in mind, we have to respond to something that "pops up in front of us" before returning to the interrupted task. Using parameter estimates from a reinforcement-learning model, we analyzed EEG data to identify neural correlates of two discrete modes of cognitive control that act to minimize interference between perception and WM. Proactive control, indexed by frontal midline theta power, increased prior to trial onset when a high level of conflict was expected. Reactive control acted to suppress the representation of items likely to interfere with performance, a processing step with consequences for the subsequent trial.

neuroscience↗

bioRxiv2023

Experimental structures of antibody/MHC-I complexes reveal details of epitopes overlooked by computational prediction

Monoclonal antibodies (mAb) to major histocompatibility complex class I (MHC-I) molecules have proved to be crucial reagents for tissue typing and fundamental studies of immune recognition. To augment our understanding of epitopic sites seen by a set of anti-MHC-I mAb, we determined X-ray crystal structures of four complexes of anti-MHC-I antigen-binding fragments (Fab) bound to peptide/MHC-I/{beta}2m (pMHC-I). An anti-H2-Dd mAb, two anti-MHC-I 3 domain mAb, and an anti-{beta}2-microglobulin ({beta}2m) mAb bind pMHC-I at sites consistent with earlier mutational and functional experiments, and the structures explain allelomorph specificity. Comparison of the experimentally determined structures with computationally derived models using AlphaFold Multimer (AF-M) showed that although predictions of the individual pMHC-I heterodimers were quite acceptable, the computational models failed to properly identify the docking sites of the mAb on pMHC-I. The experimental and predicted structures provide insight into strengths and weaknesses of purely computational approaches and suggest areas that merit additional attention. ONE SENTENCE SUMMARYX-ray structures of anti-MHC-I/MHC-I complexes define epitopes overlooked by computational prediction.

immunology↗

bioRxiv2023

Tumor-selective effects of active RAS inhibition in pancreatic ductal adenocarcinoma

Broad-spectrum RAS inhibition holds the potential to benefit roughly a quarter of human cancer patients whose tumors are driven by RAS mutations. However, the impact of inhibiting RAS functions in normal tissues is not known. RMC-7977 is a highly selective inhibitor of the active (GTP-bound) forms of KRAS, HRAS, and NRAS, with affinity for both mutant and wild type (WT) variants. As >90% of human pancreatic ductal adenocarcinoma (PDAC) cases are driven by activating mutations in KRAS, we assessed the therapeutic potential of RMC-7977 in a comprehensive range of PDAC models, including human and murine cell lines, human patient-derived organoids, human PDAC explants, subcutaneous and orthotopic cell-line or patient derived xenografts, syngeneic allografts, and genetically engineered mouse models. We observed broad and pronounced anti-tumor activity across these models following direct RAS inhibition at doses and concentrations that were well-tolerated in vivo. Pharmacological analyses revealed divergent responses to RMC-7977 in tumor versus normal tissues. Treated tumors exhibited waves of apoptosis along with sustained proliferative arrest whereas normal tissues underwent only transient decreases in proliferation, with no evidence of apoptosis. Together, these data establish a strong preclinical rationale for the use of broad-spectrum RAS inhibition in the setting of PDAC.

cancer biology↗

bioRxiv2023

Epigenetic Small-Molecule Screen for Inhibition and Reversal of Acinar Ductal Metaplasia in Mouse Pancreatic Organoids

BackgroundAcinar ductal metaplasia (ADM) is among the earliest initiating events in pancreatic ductal adenocarcinoma (PDAC) development. MethodsWe developed a novel morphology-based screen using organoids from wildtype and p48Cre/+ (Cre) mice to discover epigenetic modulators that inhibit or reverse pancreatic ADM more effectively than the broad-spectrum HDAC inhibitor trichostatin A (TSA). ResultsOf the 144 compounds screened, nine hits and two additional natural product HDAC inhibitors were validated by dose-response analysis. The class I HDAC inhibitors apicidin and FK228, and the histone methyltransferase inhibitor chaetocin demonstrated pronounced ADM inhibition and reversal without inducing significant cytotoxicity at 1 {micro}M. Thioester prodrug class I HDAC inhibitor largazole attenuated ADM while its disulfide homodimer was effective in both ADM inhibition and reversal. Prioritized compounds were validated for ADM reversal in p48Cre/+;LSL-KrasG12D/+ (KC) mouse organoids using both morphological and molecular endpoints. Molecular index analysis of ADM reversal in KC mouse organoids demonstrated improved activity compared to TSA. Improved prodrug stability translated into a stronger phenotypic and molecular response. RNA-sequencing indicated that angiotensinogen was the top inhibited pathway during ADM reversal. ConclusionOur findings demonstrate a unique epigenetic mechanism and suggest that the phenotypic screen developed here may be applied to discover potential treatments for PDAC.

cancer biology↗

bioRxiv2023

Functional characterization of RNA profiles in processing bodies of human embryonic stem cells and mesodermal cells

Processing bodies (P-bodies) are the membraneless organelles that play critical roles in RNA storage and decay. Abnormalities in P-bodies contribute to diseases and developmental disorders. Huge efforts have been applied to the identification of the protein components in P-bodies, however, the dynamics of RNA components of P-bodies in human embryonic stem cells (hESCs) during maintenance and differentiation remain largely elusive. Here, we characterized the RNA profiles of P-bodies from HEK293T cells, hESCs, and hESC-derived mesodermal cells. The number of P-bodies decreases upon hESC differentiation towards mesodermal fate, accompanied with the decreased RNAs within P-bodies. By functional analysis of the P-body enriched and P-body depleted genes across different cell types, we discovered the cell type-specific enrichment of P-body-genes and the potential association with human diseases. We also captured the non-coding RNAs, including long intergenic non-coding RNAs and transposable elements in P-bodies in a cell type-specific manner. Furthermore, we verified the involvement P-bodies in regulating the differentiation of hESCs towards mesoderm by over-expression of LSM14A and knocking down of SPTAN1. In summary, we characterized the mRNAs and non-coding RNAs in P-bodies of hESCs and hESC-derived mesodermal cells, discovering the potential roles that P-bodies play for the precise differentiation of hESCs.

developmental biology↗

bioRxiv2023

Multiplicative frequency and angular speckle reduction in ultrasound imaging

Speckle is the major artifact in ultrasound imaging, and it is well-known that speckle can be reduced by compounding (averaging) images taken either at different frequencies or from different angles. By averaging images of a phantom taken over a frequency range [Formula] and a 90{degrees} span of angles, the combined speckle reduction is demonstrated to be ~ 9x compared to non-compounded images, while the reduction with frequency or angle averaging resulted in reductions of ~ 3x individually. The rf input to the transducer is altered to vary the sound frequency and the phantom is rotated with respect to the transducer to obtain different imaging angles. Numerical simulations of sound scattered by randomly distributed point scatterers showed quantitative agreement with the experiment. Using a commercial system, a 6x reduction in speckle is demonstrated imaging a human wrist. A robot arm is used to move the transducer along a circular path to acquire images at 9 angles separated by 10{degrees}. The commercial system does not allow direct control of the input to the transducer, so the broadband signal detected is Fourier filtered to obtain images at different frequencies with ~ 2x reduced frequency range. Images taken at different angles contain distortions from speed of sound variations and pressure induced by the probe. Two forms of non-rigid image registration are applied to correct for the distortions and create a higher resolution composite image. A design for achieving ~10x speckle reduction with essentially no loss in imaging speed is described.

bioengineering↗

bioRxiv2023

LET-381/FoxF and UNC-30/Pitx2 control the development of C. elegans mesodermal glia that regulate motor behavior.

While most CNS glia arise from neuroectodermal progenitors, some, like microglia, are mesodermally derived. To understand mesodermal glia development and function, we investigated C. elegans GLR glia, which ensheath the brain neuropil and separate it from the circulatory-system cavity. Transcriptome analysis suggests GLR glia merge astrocytic and endothelial characteristics relegated to separate cell types in vertebrates. Combined fate acquisition is orchestrated by LET-381/FoxF, a fate-specification/maintenance transcription factor expressed in glia and endothelia of other animals. Among LET-381/FoxF targets, UNC-30/Pitx2 transcription factor controls GLR glia morphology and represses alternative mesodermal fates. LET-381 and UNC-30 co-expression in naive cells is sufficient for GLR glia gene expression. GLR glia inactivation by ablation or let-381 mutation disrupts locomotory behavior and induces salt hypersensitivity, suggesting brain-neuropil activity dysregulation. Our studies uncover mechanisms of mesodermal glia development and show that like neurons, glia differentiation requires autoregulatory terminal selector genes that define and maintain the glial fate.

neuroscience↗

bioRxiv2023

Intensity-dependent effects of tDCS on motor learning are related to dopamine

Non-invasive brain stimulation techniques, such as transcranial direct current stimulation (tDCS), are popular methods for inducing neuroplastic changes to alter cognition and behaviour. One challenge for the field is to optimise stimulation protocols to maximise benefits. For this to happen, we need a better understanding of how stimulation modulates cortical functioning/behaviour. To date, there is increasing evidence for a dose-response relationship between tDCS and brain excitability, however how this relates to behaviour is not well understood. Even less is known about the neurochemical mechanisms which may drive the dose-response relationship between stimulation intensities and behaviour. Here, we examine the effect of three different tDCS stimulation intensities (1mA, 2mA, 4mA anodal motor cortex tDCS) administered during the explicit learning of motor sequences. Further, to assess the role of dopamine in the dose-response relationship between tDCS intensities and behaviour, we examined how pharmacologically increasing dopamine availability, via 100mg of levodopa, modulated the effect of stimulation on learning. In the absence of levodopa, we found that 4mA tDCS improved and 1mA tDCS impaired acquisition of motor sequences relative to sham stimulation. Conversely, levodopa reversed the beneficial effect of 4mA tDCS. This effect of levodopa was no longer evident at the 48-hour follow-up, consistent with previous work characterising the persistence of neuroplastic changes in the motor cortex resulting from combining levodopa with tDCS. These results provide the first direct evidence for a role of dopamine in the intensity-dependent effects of tDCS on behaviour.

neuroscience↗

bioRxiv2023

METI: Deep profiling of tumor ecosystems by integrating cell morphology and spatial transcriptomics

The recent advance of spatial transcriptomics (ST) technique provides valuable insights into the organization and interactions of cells within the tumor microenvironment (TME). While various analytical tools have been developed for tasks such as spatial clustering, spatially variable gene identification, and cell type deconvolution, most of them are general methods lacking consideration of histological features in spatial data analysis. This limitation results in reduced performance and interpretability of their results when studying the TME. Here, we present a computational framework named, Morphology-Enhanced Spatial Transcriptome Analysis Integrator (METI) to address this gap. METI is an end-to-end framework capable of spatial mapping of both cancer cells and various TME cell components, robust stratification of cell type and transcriptional states, and cell co-localization analysis. By integrating both spatial transcriptomics, cell morphology and curated gene signatures, METI enhances our understanding of the molecular landscape and cellular interactions within the tissue, facilitating detailed investigations of the TME and its functional implications. The performance of METI has been evaluated on ST data generated from various tumor tissues, including gastric, lung, and bladder cancers, as well as premalignant tissues. Across all these tissues and conditions, METI has demonstrated robust performance with consistency.

cancer biology↗

bioRxiv2023

Central pore-opening structure and gating of the mechanosensitive PIEZO1 channel

PIEZO1 is a mechanically activated cation channel that undergoes force-induced activation and inactivation to control diverse physiological processes1-4. However, the distinct functional states and gating transitions remain structurally undefined. In response to changes in membrane forces, PIEZO1 transitions from a curved to a flattened shape, which might lead to opening and subsequent inactivation of the ion-conducting pore5,6. Here we employed a PIEZO1 mutant to capture various conformational states including an intermediate state with an opened central pore, allowing us to reveal the gating dynamics of this multiple-gate system. Upon transition from the curved to the partially flattened intermediate state, the trimeric cap undergoes a downward and rotational motion to open the lateral cap-gate, while the loop that connects the cap to the pore-lining inner helix acts as a spring-linker, switching from an extended to a compressed state. Along with the partial flattening of the peripheral blades, these conformational changes collectively dilate the cap-gate, spring-gate and the hydrophobic transmembrane-gate, leading to ion permeation through the transmembrane pore. Upon inactivation, while the blades remain flattened, the cap and spring-linker return to an up and extended state. Molecular dynamics simulations verify the ion-permeating pathway and the distinct ion-conducting states of the assigned close, intermediate, open, and inactivated structures. Mutagenesis and electrophysiological characterizations reveal that domains and residues involved in conformational dynamics of the cap and spring-linker are critical for mechanical activation of PIEZO1. Together, these studies have structurally defined the distinct functional states and the curvature-based activation and inactivation mechanisms of PIEZO1.

neuroscience↗

bioRxiv2023

GeneCompass: Deciphering Universal Gene Regulatory Mechanisms with Knowledge-Informed Cross-Species Foundation Model

Deciphering the universal gene regulatory mechanisms in diverse organisms holds great potential to advance our knowledge of fundamental life process and facilitate research on clinical applications. However, the traditional research paradigm primarily focuses on individual model organisms, resulting in limited collection and integration of complex features on various cell types across species. Recent breakthroughs in single-cell sequencing and advancements in deep learning techniques present an unprecedented opportunity to tackle this challenge. In this study, we developed GeneCompass, the first knowledge-informed, cross-species foundation model pre-trained on an extensive dataset of over 120 million single-cell transcriptomes from human and mouse. During pre-training, GeneCompass effectively integrates four types of biological prior knowledge to enhance the understanding of gene regulatory mechanisms in a self-supervised manner. Fine-tuning towards multiple downstream tasks, GeneCompass outperforms competing state-of-the-art models in multiple tasks on single species and unlocks new realms of cross-species biological investigation. Overall, GeneCompass marks a milestone in advancing knowledge of universal gene regulatory mechanisms and accelerating the discovery of key cell fate regulators and candidate targets for drug development.

bioinformatics↗

bioRxiv2023

Multi-omics analysis reveals signatures of selection and loci associated with complex traits in pigs

Selection signatures that contribute to phenotypic diversity, especially morphogenesis in pigs, remain to be further elucidated. To reveal the regulatory role of genetic variations in phenotypic differences between Eastern and Western pig breeds, we performed a systematic analysis based on seven high-quality de novo assembled genomes, 1,081 resequencing data representing 78 domestic breeds, 162 methylomes, and 162 transcriptomes of skeletal muscle from Tongcheng (Eastern) and Landrace (Western) pigs at 27 developmental stages. Selective sweep uncovers different genetic architectures behind divergent selection directions for the Eastern and Western breeds. Notably, two loci showed functional alterations by almost fixed missense mutations. By integrating time-course transcriptome and methylome, we revealed differences in developmental timing during myogenesis between Eastern and Western breeds. Genetic variants under artificial selection have critical regulatory effects on progression patterns of heterochronic genes like GHSR and BDH1, by the interaction of local DNA methylation status, particularly during embryonic development. Altogether, our work not only provides valuable resources for understanding pig complex traits, but also contributes to human biomedical research.

genomics↗

bioRxiv2023

Partitioning heritability using single-cell multi-omics identifies a novel macrophage subpopulation conveying genetic risks of coronary artery disease.

BackgroundCoronary artery disease (CAD), the leading cause of death worldwide, is influenced by both environmental and genetic factors. While over 250 genetic risk loci have been identified through genome-wide association studies, the specific causal variants and their regulatory mechanisms are still largely unknown, particularly in disease-relevant cell types like macrophages. MethodsWe utilized single-cell RNA-seq (scRNA-seq) and single-cell multi-omics approaches in primary human monocyte-derived macrophages to explore the transcriptional regulatory network involved in a critical pathogenic event of coronary atherosclerosis--the formation of lipid-laden foam cells. Meta-analysis of scRNA-seq datasets from 26 human plaque samples was undertaken to provide a comprehensive atlas of lesional macrophages and to correlate subpopulations in vivo and ex vivo. The genetic risk levels of CAD were assessed by partitioning disease heritability across different macrophage subpopulations. ResultsWe identified a novel macrophage subpopulation, termed lipid-handling macrophages, both ex vivo and in vivo, and identified associated marker genes, transcription regulators, and functional pathways. 18,782 cis-regulatory elements were identified by jointly profiling the gene expression and chromatin accessibility of >5000 macrophages. Integration with CAD GWAS data prioritized 121 CAD-related genetic variants and 56 candidate causal genes. We showed that CAD heritability was not uniformly distributed and was particularly enriched in the gene programs of lipid-handling macrophages. We investigated the cis-regulatory effect of a risk variant rs10488763 on FDX1, implicating the recruitment of AP-1 and C/EBP-beta in the causal mechanisms at this locus. ConclusionsOur results provide genetic evidence of the divergent roles of macrophage subsets in atherogenesis and highlight lipid-handling macrophages as a key sub-population through which genetic variants actively influence disease. These findings provide an unbiased framework for functional fine-mapping of GWAS results using single-cell multi-omics and offer new insights into the genotype-environment interactions underlying atherosclerotic disease.

genetics↗

bioRxiv2023

A role for JAK2 in mediating cell surface GHR-PRLR interaction

Growth hormone (GH) receptor (GHR) and (full-length) prolactin (PRL) receptor (PRLR) are transmembrane class I cytokine receptors that co-exist in various normal and cancerous cells. Both receptors respond to their associated ligands predominantly by activating the Janus Kinase 2 (JAK2)-signal transducer and activator of transcription (STAT) signaling pathways, and both are also known to initiate receptor-specific JAK2-independent signaling. Together with their cognate ligands, these receptors have been associated with pro-tumorigenic effects in various cancers, including breast cancer (BC). Human GH is known to bind GHR and PRLR, while PRL can only bind PRLR. A growing body of work suggests that GHR and PRLR can form heteromers in BC cells, modulating GH signal transduction. However, the dynamics of PRLR and GHR on the plasma membrane and how these could affect their respective signaling still need to be understood. To this end, we set out to unravel the spatiotemporal dynamics of GHR and PRLR on the surface of human T47D breast cancer cells and {gamma}2A-JAK2 cells. We applied direct stochastic optical reconstruction microscopy (dSTORM) and quantified the colocalization and availability of both receptors on the plasma membrane at the nanometer scale at different time points following treatment with GH and PRL. In cells co-expressing GHR and PRLR, we surprisingly observed that not only GH but also PRL treatment induces a significant loss of surface GHR. In cells lacking PRLR or expressing a mutant PRLR deficient in JAK2 binding, we observed that GH induces downregulation of cell surface membrane-bound GHR, but PRL no longer induces loss of surface GHR. Colocalizations of GHR and PRLR were confirmed by proximity ligation (PL) assay. Our results suggest that PRLR-GHR interaction, direct or indirect, is indispensable for PRL- but not GH- induced loss of surface GHR and for both GH-induced and PRL-induced increase of surface PRLR, with potential consequences for downstream signaling. Furthermore, our results suggest that JAK2 binding via the receptor intracellular domains Box1 element is crucial for the observed regulation of one class I cytokine receptors cell surface availability via ligand-induced activation of another class I cytokine receptor. Our findings shed new light on the reciprocal and collective role that PRLR and GHR play in regulating cell signaling.

biophysics↗

bioRxiv2023

Genomic insights into post-domestication expansion and selection of body size in ponies

Horses domestication revolutionized human civilization by changing transportation, farming, and warfare patterns. Despite extensive studies on modern domestic horse origins, the intricate demographic history and genetic signatures of pony size demand further exploration. Here, we present a high-quality genome of the Chinese Debao pony and extensively analyzed 385 individuals from 49 horse breeds. We reveal the conservation of ancient components in East Asian horses and close relationships between Asian horses and specific European pony lineages. Genetic analysis uncovers Asian paternal origin for European pony breeds, and these pony-sized horses share a close genetic affinity due to the presence of a potential ancestral ghost pony population. Additionally, we identify promising cis-regulatory elements influencing horse withers height by regulating genes like RFLNA and FOXO1. Overall, our study provides insightful perspectives into the development history and genetic determinants underlying body size in ponies and offers broader implications for horse population management and improvement. TeaserDecoding pony genetics: exploring origins and size determinants sheds light on their historical and biological impacts.

genomics↗