Biology subjects

Xiong, Y.

Publications and source records attributed to Xiong, Y..

At least 163 records · Page 9Linked to original sources

bioRxiv2022

Sex-specific transcription and DNA methylation landscapes of the Asian citrus psyllid, a vector of huanglongbing pathogens.

The relationship of DNA methylation and sex-biased gene expression is of high interest, it allows research into mechanisms of sexual dimorphism and the development of potential novel strategies for insect pest control. The Asian citrus psyllid, Diaphorina citri Kuwayama, is a major vector for the causative agents of Huanglongbing (HLB), which presents an unparalleled challenge to citrus production worldwide. Here, we identify the X chromosome of D. citri and investigate differences in the transcription and DNA methylation landscapes between adult virgin males and females. We find a large number of male-biased genes on the autosomes and a depletion of such on the X chromosome. We have also characterised the methylome of D. citri, finding low genome-wide levels, which is unusual for an hemipteran species, as well as evidence for both promoter and TE methylation. Overall, DNA methylation profiles are similar between the sexes but with a small number of differentially methylated genes found to be involved in sex differentiation. There also appears to be no direct relationship between differential DNA methylation and differential gene expression. Our findings lay the groundwork for the development of novel epigenetic-based pest control methods, and given the similarity of the D. citri methylome to other insect species, these methods could be applicable across agricultural insect pests.

evolutionary biology↗

bioRxiv2022

cir-DNA sequencing revealed the landscape of extrachromosomal circular DNA in articular cartilage and the potential roles in osteoarthritis

ObjectiveExtrachromosomal circular DNA (eccDNA) has been shown to be involved in several physiological and pathological processes including immunity, inflammation, aging and tumor. However, the expression of eccDNA in cartilage has been not reported until now. In this study, we aimed to investigate the landscape of eccDNA in articular cartilage and analyze the potential roles in Osteoarthritis (OA). MethodsThe samples of articular cartilage were obtained from total knee arthroplasty (TKA) donors with OA. The mtDNAs (mitochondrial DNA) and the linear DNAs from chondrocytes of articular cartilage were removed. Then the eccDNAs were enriched for cir-DNA sequencing. After quality control evaluation, we systematically revealed the identified eccDNA data including size distribution, the size range and sequence pattern. Moreover, we explored and disscussed the potential roles of eccDNA in OA via motif analysis and GO/KEGG pathways analysis. ResultsThe chondrocytes from OA cartilage contained an abundance of eccDNAs, which was termed as OC-eccDNAs (OA Cartilage-derived eccDNA). The characteristics of OC-eccDNAs were tissue specific, including the distribution, the size range and sequence pattern. Moreover, the functional analysis indicated that eccDNA may be involved in the homeostasis maintenance of chondrocytes and participated in the process of OA. ConclutionsOur data firstly showed the landscape of eccDNA in articular cartilage, and preliminarily indicated the potential roles of eccDNA in OA.

molecular biology↗

bioRxiv2022

Cryo-EM structure of an active central apparatus

Accurately regulated ciliary beating in time and space is critical for diverse cellular activities, which impact the survival and development of nearly all eukaryotic species. An essential beating regulator is the conserved central apparatus (CA) of motile cilia, composed of a pair of microtubules (C1 and C2) associated with hundreds of protein subunits per repeating unit. It is largely unclear how CA plays its regulatory roles in ciliary motility. Here, we present high-resolution structures of Chlamydomonas reinhardtii CA by cryo-electron microscopy (cryo-EM) and its dynamic conformational behavior in multiple scales. The structures show how functionally related projection proteins of CA are clustered onto a spring-shaped scaffold of armadillo-repeat proteins, facilitated by elongated rachis-like proteins. The two halves of CA are brought together by elastic chain-like bridge proteins to achieve coordinated activities. We captured an array of kinesin-like protein (KLP1) in two different stepping states, which are actively correlated with beating wave propagation of cilia. These findings establish a structural framework for understanding the role of CA in cilia.

cell biology↗

bioRxiv2022

Recognition of HIV-1 capsid licenses innate immune response to viral infection

Cyclic GMP-AMP synthase (cGAS) is a primary sensor of aberrant DNA that governs an innate immune signaling cascade, leading to the induction of the type-I interferon response. We have previously identified polyglutamine binding protein 1, PQBP1, as an adaptor molecule required for cGAS-mediated innate immune response of lentiviruses, including the human immunodeficiency virus 1 (HIV-1), but dispensable for the recognition of DNA viruses. HIV-1- encoded DNA is synthesized as a single copy from its RNA genome, and is subsequently integrated into the host chromatin. HIV-1 then produces progeny through amplification and packaging of its RNA genome, thus, in contrast to DNA viruses, HIV-1 DNA is both transient and of low abundance. However, the molecular basis for the detection and verification of this low abundance HIV-1 DNA pathogen-associated molecular pattern (PAMP) is not understood. Here, we elucidate a two-factor authentication strategy that is employed by the innate immune surveillance machinery to selectively respond to the low concentration of PAMP, while discerning these species from extranuclear DNA molecules. We find that, upon HIV-1 infection, PQBP1 decorates intact viral capsid, which serves as a primary verification step for the viral nucleic acid cargo. As the reverse transcription and capsid disassembly initiate, cGAS protein is then recruited to the capsid in a PQBP1-dependent manner, enabling cGAS molecules to be co-positioned at the site of PAMP generation. Thus, these data indicate that PQBP1 recognition of the HIV-1 capsid sanctions a robust cGAS-dependent response to a limited abundance and short-lived DNA PAMP. Critically, this illuminates a molecular strategy wherein the modular recruitment of co-factors to germline encoded pattern recognition receptors (PRRs) serves to enhance repertoire of pathogens that can be sensed by the innate immune surveillance machinery.

molecular biology↗

bioRxiv2021

Monospecific and bispecific monoclonal SARS-CoV-2 neutralizing antibodies that maintain potency against B.1.617

COVID-19 pathogen SARS-CoV-2 has infected hundreds of millions and caused over 5 million deaths to date. Although multiple vaccines are available, breakthrough infections occur especially by emerging variants. Effective therapeutic options such as monoclonal antibodies (mAbs) are still critical. Here, we report the development, cryo-EM structures, and functional analyses of mAbs that potently neutralize SARS-CoV-2 variants of concern. By high-throughput single cell sequencing of B cells from spike receptor binding domain (RBD) immunized animals, we identified two highly potent SARS-CoV-2 neutralizing mAb clones that have single-digit nanomolar affinity and low-picomolar avidity, and generated a bispecific antibody. Lead antibodies showed strong inhibitory activity against historical SARS-CoV-2 and several emerging variants of concern. We solved several cryo-EM structures at [~]3 [A] resolution of these neutralizing antibodies in complex with prefusion spike trimer ectodomain, and revealed distinct epitopes, binding patterns, and conformations. The lead clones also showed potent efficacy in vivo against authentic SARS-CoV-2 in both prophylactic and therapeutic settings. We also generated and characterized a humanized antibody to facilitate translation and drug development. The humanized clone also has strong potency against both the original virus and the B.1.617.2 Delta variant. These mAbs expand the repertoire of therapeutics against SARS-CoV-2 and emerging variants.

immunology↗

bioRxiv2021

Enhancer RNA-based modeling of adverse events and objective responses of immunotherapy

Immune checkpoint inhibitors (ICI) targeting PD-1/PD-L1 or CTLA-4 are emerging and effective immunotherapy strategies. However, ICI treated patients present heterogeneous responses and adverse events, thus demanding effective ways to assess benefit over risk before treatment. Here, by integrating pan-cancer clinical and molecular data, we tried to predict immune-related adverse events (irAEs, risk) and objective response rates (ORRs, benefit) based on enhancer RNAs (eRNAs) expression among patients receiving anti-PD-1/PD-L1 therapy. We built two effective regression models, explaining 71% variance (R=0.84) of irAEs with three eRNAs and 79% (R=0.89) of ORRs with five eRNAs. Interestingly, target genes of irAE-related enhancers, including upstream regulators of MYC, were involved in metabolism, inflammation, and immune activation, while ORR-related enhancers target PAK2 and DLG1 which directly participate in T cell activation. Our study provides references for the identification of immunotherapy-related biomarkers and potential therapeutic targets during immunotherapy.

bioinformatics↗

bioRxiv2021

A luciferase prosubstrate and a red bioluminescent calcium indicator to image neuronal activity

Genetically encoded fluorescent indicators have been broadly used to monitor neuronal activity in live animals, but invasive surgical procedures are required. This study presents a functional bioluminescence imaging (fBLI) method for recording the activity of neuronal ensembles in the brain in awake mice. We developed a luciferase prosubstrate activatable in vivo by nonspecific esterase to enhance the brain delivery of the luciferin. We further engineered a bright, bioluminescent indicator with robust responsiveness to calcium ions (Ca2+) and appreciable emission above 600 nm. Integration of these advantageous components enabled the imaging of Ca2+ dynamics in awake mice minimally invasively with excellent signal- to-background and subsecond temporal resolution. This study thus establishes a new paradigm for studying brain functions in health and disease.

neuroscience↗

bioRxiv2021

Unconventional secretion of unglycosylated ORF8 is critical for the cytokine storm during SARS-CoV-2 infection

Coronavirus disease 2019 is a respiratory infectious disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Evidence on the pathogenesis of SARS-CoV-2 is accumulating rapidly. In addition to structural proteins such as Spike and Envelope, the functional roles of non-structural and accessory proteins in regulating viral life cycle and host immune responses remain to be understood. Here, we show that open reading frame 8 (ORF8) acts as messenger for inter-cellular communication between alveolar epithelial cells and macrophages during SARS-CoV-2 infection. Mechanistically, ORF8 is a secretory protein that can be secreted by infected epithelial cells via both conventional and unconventional secretory pathways. The unconventionally secreted ORF8 recognizes the IL17RA receptor of macrophages and induces cytokine release. However, conventionally secreted ORF8 cannot bind to IL17RA due to N-linked glycosylation. Furthermore, we found that Yip1 interacting factor homolog B (YIF1B) is a channel protein that translocates unglycosylated ORF8 into vesicles for unconventional secretion. Blocking the unconventional secretion of ORF8 via a YIF1B knockout in hACE2 mice attenuates inflammation and yields delayed mortality following SARS-CoV-2 challenge.

microbiology↗

bioRxiv2021

Drug specific transcriptomic signatures in healthy human subject iPSC derived cardiomyocytes

Drug-induced gene expression profiles can identify potential mechanisms of toxicity. We focused on obtaining signatures for cardiotoxicity of FDA-approved tyrosine kinase inhibitors (TKIs) in human induced pluripotent stem cell-derived cardiomyocytes. Using bulk transcriptomics profiles, we applied singular value decomposition to identify drug-selective patterns in cell lines obtained from multiple healthy human subjects. Cellular pathways affected by highly cardiotoxic TKIs include energy metabolism, contractile, and extracellular matrix dynamics. Projecting these pathways to single cell expression profiles indicates that TKI responses can be evoked in both cardiomyocytes and fibroblasts. Whole genome sequences of the cell lines, using outlier responses enabled us to correctly reidentify a genomic variant associated with anthracycline cardiotoxicity and predict genomic variants potentially associated with TKI cardiotoxicity. We conclude that mRNA expression profiles when integrated with publicly available genomic, pathway, and single cell transcriptomic datasets, provide multiscale predictive understanding of cardiotoxicity for drug development and patient stratification. One sentence summaryGenes, pathways, and cell types of the human heart associated with antineoplastic drug cardiotoxicity.

systems biology↗

bioRxiv2021

A molecular switch between mammalian MLL complexes dictates response to Menin-MLL inhibition

The chromatin adaptor Menin interacts with oncogenic fusion proteins encoded by MLL1-rearrangements (MLL1-r), and small molecules that disrupt these associations are currently in clinical trials for the treatment of leukemia. By integrating chromatin-focused and genome-wide CRISPR screens with genetic, pharmacological, and biochemical approaches in mouse and human systems, we discovered a molecular switch between the MLL1-Menin and MLL3/4-UTX chromatin modifying complexes that dictates response to Menin-MLL inhibitors. We show that MLL1-Menin safeguards leukemia survival by impeding binding of the MLL3/4-UTX complex at a subset of target gene promoters. Disrupting the interaction between Menin and MLL1 leads to UTX-dependent transcriptional activation of a tumor suppressor gene-program that is crucial for a therapeutic response in murine and human leukemia. We establish the therapeutic relevance of this mechanism by showing that CDK4/6 inhibitors allow re-activation of this tumor-suppressor program in Menin-inhibitor insensitive leukemia cells, mitigating treatment resistance. The discovery of a molecular switch between MLL1-Menin and MLL3/4-UTX complexes on chromatin sheds light on novel functions of these evolutionary conserved epigenetic mediators and is particularly relevant to understand and target molecular pathways determining response and resistance in ongoing phase 1/2 clinical trials.

cancer biology↗

bioRxiv2021

Accurate Name Entity Recognition for Biomedical Literatures: A Combined High-quality Manual Annotation and Deep-learning Natural Language Processing Study

A combined high-quality manual annotation and deep-learning natural language processing study is reported to make accurate name entity recognition (NER) for biomedical literatures. A home-made version of entity annotation guidelines on biomedical literatures was constructed. Our manual annotations have an overall over 92% consistency for all the four entity types -- gene, variant, disease and species --with the same publicly available annotated corpora from other experts previously. A total of 400 full biomedical articles from PubMed are annotated based on our home-made entity annotation guidelines. Both a BERT-based large model and a DistilBERT-based simplified model were constructed, trained and optimized for offline and online inference, respectively. The F1-scores of NER of gene, variant, disease and species for the BERT-based model are 97.28%, 93.52%, 92.54% and 95.76%, respectively, while those for the DistilBERT-based model are 95.14%, 86.26%, 91.37% and 89.92%, respectively. The F1 scores of the DistilBERT-based NER model retains 97.8%, 92.2%, 98.7% and 93.9% of those of BERT-based NER for gene, variant, disease and species, respectively. Moreover, the performance for both our BERT-based NER model and DistilBERT-based NER model outperforms that of the state-of-art model--BioBERT, indicating the significance to train an NER model on biomedical-domain literatures jointly with high-quality annotated datasets.

bioinformatics↗

bioRxiv2021

Broad neutralizing nanobody against SARS-CoV-2 engineered from pre-designed synthetic library

SARS-CoV-2 infection is initiated with Spike glycoprotein binding to the receptor of human angiotensin converting enzyme 2 via its receptor binding domain. Blocking this interaction is considered as an effective approach to inhibit virus infection. Here we report the discovery of a neutralizing nanobody, VHH60, directly produced from a humanized synthetic nanobody library. VHH60 competes with human ACE2 to bind the receptor binding domain of the Spike protein with a KD of 2.56 nM, inhibits infections of both live SARS-CoV-2 and pseudotyped viruses harboring wildtype, escape mutations and prevailing variants at nanomolar level. VHH60 also suppresses SARS-CoV-2 infection and propagation 50-fold better and protects mice from death two times longer than that of control group after live virus inoculation on mice. VHH60 therefore is a powerful synthetic nanobody with a promising profile for disease control against COVID19.

microbiology↗

bioRxiv2021

Differences between intrinsic and acquired nucleoside analogue resistance in acute myeloid leukaemia cells

BackgroundSAMHD1 mediates resistance to anti-cancer nucleoside analogues, including cytarabine, decitabine, and nelarabine that are commonly used for the treatment of leukaemia, through cleavage of their triphosphorylated forms. Hence, SAMHD1 inhibitors are promising candidates for the sensitisation of leukaemia cells to nucleoside analogue-based therapy. Here, we investigated the effects of the cytosine analogue CNDAC, which has been proposed to be a SAMHD1 substrate, in the context of SAMHD1. MethodsCNDAC was tested in 13 acute myeloid leukaemia (AML cell lines), in 26 acute lymphoblastic leukaemia cell lines, ten AML sublines adapted to various antileukaemic drugs, 24 single cell-derived clonal AML sublines, and primary leukaemic blasts from 24 AML patients. Moreover, 24 CNDAC-resistant sublines of the AML cell lines HL-60 and PL-21 were established. The SAMHD1 gene was disrupted using CRISPR/Cas9 and SAMHD1 depleted using RNAi, and the viral Vpx protein. Forced DCK expression was achieved by lentiviral transduction. SAMHD1 promoter methylation was determined by PCR after treatment of genomic DNA with the methylation-sensitive HpaII endonuclease. Nucleoside (analogue) triphosphate levels were determined by LC-MS/MS. CNDAC interaction with SAMHD1 was analysed by an enzymatic assay and by crystallisation. ResultsAlthough the cytosine analogue CNDAC was anticipated to inhibit SAMHD1, SAMHD1 mediated intrinsic CNDAC resistance in leukaemia cells. Accordingly, SAMHD1 depletion increased CNDAC triphosphate (CNDAC-TP) levels and CNDAC toxicity. Enzymatic assays and crystallisation studies confirmed CNDAC-TP to be a SAMHD1 substrate. In 24 CNDAC-adapted acute myeloid leukaemia (AML) sublines, resistance was driven by DCK (catalyses initial nucleoside phosphorylation) loss. CNDAC-adapted sublines displayed cross-resistance only to other DCK substrates (e.g. cytarabine, decitabine). Cell lines adapted to drugs not affected by DCK or SAMHD1 remained CNDAC sensitive. In cytarabine-adapted AML cells, increased SAMHD1 and reduced DCK levels contributed to cytarabine and CNDAC resistance. ConclusionIntrinsic and acquired resistance to CNDAC and related nucleoside analogues are driven by different mechanisms. The lack of cross-resistance between SAMHD1/ DCK substrates and non-substrates provides scope for next-line therapies after treatment failure.

pharmacology and toxicology↗

bioRxiv2021

Based on the identification of tumor antigens and immune subtypes in renal clear cell carcinoma for mRNA vaccine development

BackgroundCancer vaccine based on mRNA is considered as a promising strategy and has become a new hot spot in cancer immunotherapy. However, its application to KIRC is not clear. A growing body of research has shown that immunotyping can reflect the comprehensive immune status and immune microenvironment of tumor, which is closely related to treatment response and vaccination potential. The aim of this study was to identify the potential antigens of KIRC for the development of anti-KIRC mRNA vaccines, and to further differentiate the immune subtypes of KIRC to construct an immune landscape for the selection of appropriate patients for vaccination. MethodsGene expression profiles and corresponding clinical information of 265 KIRC patients and RNA-seq data of 539 KIRC patients were retrieved from were collected from GEO and TCGA. cBioPortal was used to visualize and compare genetic alterations, while GEPIA2 was used to calculate the prognostic index of selected antigens. The relationship between the infiltration of antigen presenting cells and the expression of the identified antigen was visualized with TIMER, and consensus clustering analysis was used to determine the immune subtypes. Finally, the immune landscape of KIRC is visualized through the dimensionality reduction analysis based on graph learning. ResultsTwo tumor antigens associated with prognostic and antigen-presenting infiltrating cells were identified in KIRC, including LRP2, and DOCK8. KIRC patients were classified into six immune subtypes based on different molecular, cellular, and clinical characteristics. Patients with IS5 and IS6 tumors had an immune "hot" and immunosuppressive phenotype, which was associated with better survival compared to other subtypes, whereas patients with IS1-4 tumors had an immune "cold" phenotype, which was associated with a higher tumor mutation burden. In addition, the expression of immune checkpoints and immunogenic cell death modulators differed significantly in different immunosubtypes of tumors. Finally, the immune landscape of KIRC shows a high degree of heterogeneity across patients. ConclusionsLRP2 and FEM2 are potential KIRC antigens for mRNA vaccine development, and patients with immune subtypes IS1-4 are suitable for vaccination.

bioinformatics↗

bioRxiv2021

Callosal fiber length scales with brain size according to functional lateralization, evolution, and development

Brain size significantly impacts the organization of white matter fibers. Fiber length scaling - the degree to which fiber length varies according to brain size - was overlooked. We investigated how fiber lengths within the corpus callosum, the most prominent white matter tract, vary according to brain size. The results showed substantial variation in length scaling among callosal fibers, replicated in two large healthy cohorts ([~]2000 individuals). The underscaled callosal fibers mainly connected the precentral gyrus and parietal cortices, whereas the overscaled callosal fibers mainly connected the prefrontal cortices. The variation in such length scaling was biologically meaningful: larger scaling corresponded to larger neurite density index but smaller fractional anisotropy values; cortical regions connected by the callosal fibers with larger scaling were more lateralized functionally as well as phylogenetically and ontogenetically more recent than their counterparts. These findings highlight an interaction between interhemispheric communication and organizational and adaptive principles underlying brain development and evolution. Significance StatementBrain size varies across evolution, development, and individuals. Relative to small brains, the neural fiber length in large brains is inevitably increased, but the degree of such increase may differ between fiber tracts. Such a difference, if it exists, is valuable for understanding adaptive neural principles in large versus small brains during evolution and development. The present study showed a substantial difference in the length increase between the callosal fibers that connect the two hemispheres, replicated in two large healthy cohorts. Altogether, our study demonstrates that reorganization of interhemispheric fibers length according to brain size is intrinsically related to fiber composition, functional lateralization, cortical myelin content, evolutionary and developmental expansion.

neuroscience↗

bioRxiv2021

Comparative genomics reveals evolutionary drivers of sessile life and left-right shell asymmetry in bivalves

Bivalves are species-rich mollusks with prominent protective roles in coastal ecosystems. Across these ancient lineages, colony-founding larvae anchor themselves either by byssus production or by cemented attachment. The latter mode of sessile life is strongly molded by left-right shell asymmetry during larval development of Ostreoida oysters such as Crassostrea hongkongensis. Here, we sequenced the genome of C. hongkongensis in high resolution and compared it to reference bivalve genomes to unveil genomic determinants driving cemented attachment and shell asymmetry. Importantly, loss of the homeobox gene antennapedia (Antp) and broad expansion of lineage-specific extracellular gene families are implicated in a shift from byssal to cemented attachment in bivalves. Evidence from comparative transcriptomics shows that the left-right asymmetrical C. hongkongensis plausibly diverged from the symmetrical Pinctada fucata in expression profiles marked by elevated activities of orthologous transcription factors and lineage-specific shell-related gene families including tyrosinases, which may cooperatively govern asymmetrical shell formation in Ostreoida oysters.

genomics↗

bioRxiv2021

Direct sulphate-TOR signalling controls transcriptional reprogramming for shoot apex activation in Arabidopsis

Photosynthetic plants play a primary role for the global sulphur cycle in the earth ecosystems by reduction of inorganic sulphate from the soil to organic sulphur-containing compounds. How plants sense and transduce the sulphate availability in soil to mediate their growth remains largely unclear. The target of rapamycin (TOR) kinase is an evolutionarily conserved master regulator of nutrient sensing and metabolic signalling to control cell proliferation and growth in all eukaryotes. Here, we discovered that inorganic sulphate exhibits higher potency than organic cysteine and glutathione for activation of TOR and cell proliferation in the leaf primordium to promote true leaf development in Arabidopsis. Chemical genetic analyses further revealed that this sulphate activation of TOR is independent of the sulphate-assimilation process and glucose-energy signalling. Significantly, tissue specific transcriptome analyses uncovered previously unknown sulphate-orchestrating genes involved in DNA replication, cell proliferation, autophagy and various secondary metabolism pathways, which are completely depending on TOR signalling. Systematic comparison between the sulphate- and glucose-TOR controlled transcriptome further revealed that, as the central growth integrator, TOR kinase can sense different upstream nutrient signals to control both shared and unique transcriptome networks, therefore, precisely modulate plant proliferation, growth and stress responses.

plant biology↗

bioRxiv2021

NF-kB-repressed Sirt3 mediates testicular cholesterol metabolism and cytoskeleton assembly by P450scc/SOD2 deacetylation

Testicular homeostasis requires the balanced interplay between specific molecules in Sertoli cells, Leydig cells, germ cells. Loss of this coordination can lead to the disruption of spermatogenesis, even male infertility. By operating the upregulation and downregulation of Sirt3 in our male subfertility rats model and two testicular cells models, we indicated that Sirt3 overexpression and activator ameliorated cholesterol metabolism via P450scc deacetylation in Leydig cells, and cytoskeleton assembly via PDLIM1 with SOD2 deacetylation in Sertoli cells and elongating spermatids. In terms of the upstream regulator of Sirt3, the phosphorylation of NF-{kappa}B p65Ser536 stimulated the nuclear translocation of NF-{kappa}B subunits (p50, p65, RelB), which bound to TFBS1 and TFBS2 synchronously in the promoter of Sirt3, repressing Sirt3 transcription. This study demonstrates that NF-{kappa}B-repressed SIRT3 acts directly on cholesterol metabolism of Leydig cells and cytoskeleton assembly of Sertoli cells via P450scc/SOD2 deacetylation to regulate sperm differentiation, influencing spermatogenesis, even male fertility. Research organism: Rat, mouse

developmental biology↗