Biology subjects

Su, P.

Publications and source records attributed to Su, P..

At least 19 recordsLinked to original sources

bioRxiv2026

Telomerase RNA regulates the epigenome primed for human lineage commitment

Telomerase RNA (TERC) is known as the essential template for telomere elongation. Here, we report an unexpected role for TERC in regulating chromatin accessibility, which is primed for determining the cell fate of human embryonic stem cells (hESCs). TERC-deficient hESCs retain critical markers for pluripotency but fail to undergo lineage differentiation as shown by standard in vivo teratoma formation as well as in vitro differentiation assays, which is consistent with repressed transcription during differentiation into the three germ lineages. Notably, transient re-introduction of TERC into TERC-deficient hESCs rescued lineage differentiation capacity without restoring telomere length. TERC binds to the promoters and enhancers of developmental genes marked by H3K27ac to maintain an open chromatin state. Loss of TERC reduces H3K27ac deposition and decreases chromatin accessibility through the remodelling of three-dimensional genome organization, including TAD boundary insulation and compartment switching. Collectively, our findings reveal that TERC is a chromatin-associated noncoding RNA that regulates the epigenomic architecture that governs cell fate for lineage commitment during development.

cell biology↗

bioRxiv2026

Biosynthesis of bisbenzylisoquinoline alkaloids

Bisbenzylisoquinoline alkaloids (bisBIAs) are pharmacologically valuable plant metabolites with complex stereochemical architectures, yet the catalytic principles governing their assembly have remained largely unclear. Here, we elucidate the enzymatic pathway to cyclic bisBIAs and uncover a non-canonical redox-mediated mechanism for post-assembly stereochemical control. We identify cytochrome P450 enzymes that catalyze regioselective oxidative dimerization and macrocyclization of benzylisoquinoline monomers, establishing the macrocyclic scaffold. Subsequent stereochemical specification is achieved by a paired oxidase-reductase module that selectively epimerizes a single stereocenter through a transient imine formation, converting (R,S)-configured intermediates to (S,S)-products. Reconstitution of the pathway in yeast enabled production of both native bisBIAs and non-natural analogs, demonstrating pathway modularity and engineering potential. These results establish the biochemical principle underlying bisBIA biosynthesis and provide a framework for programmable biosynthesis of these complex natural products.

biochemistry↗

bioRxiv2025

An inherent T cell-activating mRNA delivery platform for in vivo CAR T generation

The clinical success of CAR T cell therapy has underscored the need for scalable, non-invasive strategies for in vivo T cell engineering. Although mRNA delivery offers a promising alternative, current lipid-based vectors lack intrinsic T cell tropism and often rely on antibody conjugation, complicating manufacturing and raising safety concerns. Here we present an inherent T cell-activating polymer-lipid nanoparticle (ERTLNPs) that enable ligand-free, efficient mRNA transfection and activation of T cells in vivo. ERTLNPs, composed of p-toluenesulfonyl arginine (RT)-functionalized polyethylenimine (denoted as PEI-RT) and helper lipids, preferentially accumulate in the spleen following systemic administration. Without exogenous stimulation, ERTLNPs intrinsically activate T cells, triggering robust mRNA expression and proliferation. Mechanistically, ERTLNPs engage the PI3K/AKT/mTOR signaling axis to reprogram T cell metabolism, promoting expansion while restraining exhaustion. Systemic delivery of mRNA encoding fibroblast activation protein chimeric antigen receptor (mFAP CAR) via ERTLNPs leads to in situ generation of functional CAR T cells, which efficiently eliminate pathological fibroblasts in models of cancer and fibrosis, with minimal off-target effects. This ligand-free, metabolically reprogramming mRNA delivery platform provides a clinically translatable approach for in vivo CAR T cell generation and broadens the landscape of non-viral immunotherapeutic engineering.

bioengineering↗

bioRxiv2025

A multi-tissue atlas of genetic regulatory effects in sheep

Characterizing the impact of genomic variants on genome function and ultimately complex traits in livestock is essential for the development of sustainable precision agriculture and comparative genomics. Here, as part of the Farm animal Genotype-Tissue Expression (FarmGTEx) project, we present the pilot phase of the SheepGTEx resource through analyzing 6,761 RNA-sequencing samples of 51 primary tissues in a multi-breed population of sheep. We identify millions of regulatory variants associated with seven types of molecular phenotypes, and fine-map 322,468 primary and 114,017 non-primary effects, revealing a high degree of regulatory allelic heterogeneity. We systematically characterize the pleiotropic effects of these variants on molecular phenotypes, assess their context-specific regulatory patterns across tissues, breeds, sexes, and developmental stages, as well as explore their evolutionary constraints across mammals. Finally, we demonstrate the substantial potential of the SheepGTEx resource (https://sheepgtex.farmgtex.org), by providing examples of regulatory mechanisms underpinning 34 complex traits, population divergence between European and Asian breeds, and adaptive evolution in sheep over the past ten millennia.

genomics↗

bioRxiv2025

scRNA + TCR + BCR-seq Reveals the proportion and characteristics of dual TCR T cells and dual BCR B cells in mice infected with Echinococcus granulosus

Cystic echinococcosis (CE) is a zoonotic parasitic disease caused by Echinococcus granulosus, and the T and B cell responses and regulatory mechanisms in CE remain unclear. In this study, we analyzed the data of peripheral blood and spleen of mice infected with Echinococcus granulosus(EG) by scRNA+TCR+BCR-seq, and made the following novel findings: (1) Peripheral blood of Echinococcus granulosus (EG)-infected mice contained a higher proportion of dual TCR(T cell receptor) T cells with higher clonality than uninfected mice; (2) There was a bias in V gene usage between single TCR T and dual TCR T cells, as well as between single BCR(B cell receptor) B cells and dual BCR B cells in EG-infected mice; (3) Dual TCR Tregs, dual TCR effector CD8 T cells, dual BCR Bregs, and dual BCR memory/dividing B cells exhibited relatively high clonal expansion in EG-infected mice; (4) Shared CDR3 sequences and consistently highly expressed mRNA molecules exist between single receptor T/B and dual receptor T/B cells in EG-infected mice. KEGG enrichment analysis revealed that dual BCR B cells are closely related to the expression of factors associated with pathways such as "Th1/Th2 differentiation" and "antigen processing and presentation". These results suggest that dual TCR T and dual BCR B cells may be involved in the specific responses and regulation of EG-infected mice, providing a novel perspective for the adaptive immune response mechanisms and targeted therapy of parasitic infections. Author summaryEchinococcosis is a zoonotic disease currently prevalent mainly in various parts of Africa. At present, it cannot be completely cured; treatment relies solely on medication to alleviate symptoms. The immunoregulatory mechanisms underlying the disease remain unclear. Using single-cell RNA sequencing, we have identified a novel T- and B-cell subpopulation that may play a role in the immune response to the parasite. This finding opens a new avenue for researchers investigating parasitic diseases.

immunology↗

bioRxiv2025

Direct Readout of Multivalent Chromatin Reader-Nucleosome Interactions by Nucleosome Mass Spectrometry

Histone post-translational modifications (PTMs) often serve as distinct recognition sites for the recruitment of chromatin-associated proteins (CAPs) for epigenome regulation. While CAP-PTM interactions have been extensively studied using histone peptides, this cannot consider the regulatory potential of multi-site binding on intact nucleosomes. To overcome this limitation, we applied Nucleosome Mass Spectrometry (Nuc-MS), a native Top-Down MS approach that enables controlled disassembly of intact CAP:nucleosome (CAP:nuc) complexes to provide a direct readout of the contained histone proteoforms. As proof of principle, we show the BPTF PHD-BD native tandem reader requires coincident H3K4me3K9acK14acK18ac for effective nucleosome engagement. We extend our approach to explore how the BRD4 (native BD1-BD2), DNMT3A-MPP8 (chimeric PWWP-CD), and PtSHL (native BAH-BD) tandem readers interact with endogenous nucleosomes. Each reveals distinct enrichment profiles: BRD4 favoring di- and tri-acetylated histone H4 proteoforms, whereas DNMT3A-MPP8 and PtSHL preferentially interact with hypermethylated H3 proteoforms. Of note the latter enriches combinatorial {H3K4me3K27me3} on the same histone tail in HeLa chromatin, and thus expands the potential biology of this widely studied bivalent signature. By directly characterizing CAP:nuc complex composition with combinatorial PTM information in a single readout, Nuc-MS serves as a new approach to discover the modifications driving binding, and therefore primary candidates to explore for structural biology and genomic studies. O_FIG O_LINKSMALLFIG WIDTH=199 HEIGHT=200 SRC="FIGDIR/small/651740v1_ufig1.gif" ALT="Figure 1"> View larger version (32K): org.highwire.dtl.DTLVardef@8815e9org.highwire.dtl.DTLVardef@5685b5org.highwire.dtl.DTLVardef@643881org.highwire.dtl.DTLVardef@1b9bc20_HPS_FORMAT_FIGEXP M_FIG O_FLOATNOFor TOC only.C_FLOATNO Synopsis. Nuc-MS provides the ability to control the disassembly of chromatin-associated protein-nucleosome complexes (CAP-nuc) and delineate the histone proteoforms driving tandem reader domain binding. C_FIG

biochemistry↗

bioRxiv2024

Ecological Scaling of Temporal Fluctuations with Bacterial Abundance in Gut Microbiota Depends on Functional Properties of Individual Microbial Species and Bacterial Communities

Macroecological relationships that describe various statistical associations between species abundances, their spatial, and temporal variability are among the most general laws in ecology and biology. One of the most commonly observed relationships is a power-law scaling between means and variances of temporal species abundances, known in ecology as Taylors law. Taylors law has been observed across many ecosystems, from diverse plant and animal ecosystems to complex microbial communities. While many mathematical models have been proposed to explain the potential origins of Taylors law, what determines its scaling exponents across species and ecosystems is not understood. Here, we use temporal trajectories of human and baboon gut microbiota to analyze the relationship between functional properties of individual bacterial species and microbial communities with the scaling of species-specific and community-level Taylors law. The species Taylor law characterizes - for each individual species - the relationship between the species temporal abundance means and temporal abundance variances across host organisms. On the other hand, community-level Taylors law characterizes - in each host organism - the scaling across multiple species between their temporal abundance means and temporal abundance variances. For community Taylors law, we find that the power law scaling is strongly associated with the microbiota abundance of certain nutrient-degrading enzymes in the gut. Notably, our results demonstrate that the availability of enzymes metabolizing starch glycogen significantly increases Taylors law scaling. We also find that species Taylors law depends on the individual species functional properties. Specifically, we observe lower Taylors law scaling for species with larger metabolic networks, for species that are able to grow on a larger number of carbon sources, and for species with particular metabolic functions, such as glutamine and folate metabolism. Overall, our study reveals that Taylors law scaling is strongly associated with the functional capabilities of bacterial communities and individual microbial species biosynthetic properties, which are likely related to their ecological roles in the gut microbiota.

microbiology↗

bioRxiv2024

Correlative Imaging for Comprehensive Molecular Mapping of Individual Cell Types in Biological Tissues

Mass spectrometry imaging (MSI) is a powerful technique for label-free spatial mapping of multiple classes of biomolecules in tissue sections. However, differences in desorption and ionization efficiency of different classes of molecules make it challenging to simultaneously map biomolecules at each omics layer in the same tissue sample. Herein, we present a correlative imaging method using nanospray desorption electrospray ionization (nano-DESI) MSI, which enables the spatial mapping of lipids, metabolites, peptides, and proteins with cellular-level spatial resolution in a single tissue section. We demonstrate the molecular profiling of specific cell types and identify truncated peptides in mouse pancreatic tissue. Distinct chemical gradients of peptides and lipids extending from endocrine cells to exocrine cells indicate their different roles in endocrine-exocrine crosstalk and intracellular signaling. The results underscore the power of the developed imaging approach for spatial multi-omics analysis that provides deep insights into cellular diversity and the intricate molecular interactions that occur within heterogenous biological tissues.

biochemistry↗

bioRxiv2024

The role of conscious attention in statistical learning: evidence from patients with impaired consciousness

The debate over whether conscious attention is necessary for statistical learning has produced mixed and conflicting results. Testing individuals with impaired consciousness may provide some insight, but very few studies have been conducted due to the difficulties associated with testing such patients. In this study, we examined the ability of patients with varying levels of consciousness disorders (DOC), including coma, unresponsive wakefulness syndrome, minimally conscious patients, and emergence from minimally conscious state patients, to extract statistical regularities from an artificial language composed of four randomly concatenated pseudowords. We used a methodology based on frequency tagging in EEG, which was developed in our previous studies on speech segmentation in sleeping neonates. Our study had two main objectives: firstly, to assess the automaticity of the segmentation process and explore correlations between the level of covert consciousness and the abilities to extract statistical regularities, second, to explore a potential new diagnostic indicator to aid in patient management by examining the correlation between successful statistical learning markers and consciousness level. We observed that segmentation abilities were preserved in some minimally conscious patients, suggesting that statistical learning is an inherently automatic low-level process. Due to significant inter-individual variability, word segmentation may not be a sufficiently robust candidate for clinical use, unlike temporal accuracy of auditory syllable responses, which correlates strongly with coma severity. Therefore, we propose that frequency tagging of an auditory stimulus train, a simple and robust measure, should be further investigated as a possible metric candidate for DOC diagnosis.

neuroscience↗

bioRxiv2023

The Natural Products Discovery Center: Release of the First 8490 Sequenced Strains for Exploring Actinobacteria Biosynthetic Diversity

Actinobacteria, the bacterial phylum most renowned for natural product discovery, has been established as a valuable source for drug discovery and biotechnology but is underrepresented within accessible genome and strain collections. Herein, we introduce the Natural Products Discovery Center (NPDC), featuring 122,449 strains assembled over eight decades, the genomes of the first 8490 NPDC strains (7142 Actinobacteria), and the online NPDC Portal making both strains and genomes publicly available. A comparative survey of RefSeq and NPDC Actinobacteria highlights the taxonomic and biosynthetic diversity within the NPDC collection, including three new genera, hundreds of new species, and [~]7000 new gene cluster families. Selected examples demonstrate how the NPDC Portals strain metadata, genomes, and biosynthetic gene clusters can be leveraged using genome mining approaches. Our findings underscore the ongoing significance of Actinobacteria in natural product discovery, and the NPDC serves as an unparalleled resource for both Actinobacteria strains and genomes.

microbiology↗

bioRxiv2023

High clonal diversity and spatial genetic admixture in early prostate cancer and surrounding normal tissue

Somatic copy number alterations (SCNAs) are pervasive in advanced human cancers, but their prevalence and spatial distribution in early-stage, localized tumors and their surrounding normal tissues are poorly characterized. Here, we performed multi-region, single-cell DNA sequencing to characterize the SCNA landscape across multiple tumor-rich and normal tissue regions ([~]125 mm3 tissue cubes) obtained from prostatectomy performed in two patients with localized prostate cancer. We identified two distinct populations of cells with abnormal karyotypes, one marked by sparse deletions or amplifications ( pseudo-diploid cells) and the second characterized by genome-wide copy number changes reminiscent of monster cells previously described in colorectal cancer. Pseudo-diploid cells formed numerous small-sized subclones ranging from highly spatially localized to broadly spread subclones mainly featuring (sub-)chromosomal arm deletions. In contrast, monster cells harbored whole-chromosome gains and losses and were mostly singular events detected throughout the prostate, including normal tissue regions. Targeted deep sequencing of cancer-associated genes revealed a more confined pattern of mutations overlapping with tumor-rich regions, although we also detected mutations in regions deemed normal based on morphological assessment and bulk RNA-seq. Highly localized pseudo-diploid subclones were confined within tumor-rich regions and typically carried deletions involving chromosome (chr) 6 and 13, resulting in simultaneous loss of multiple tumor-suppressor genes, including FOXO1 and FOXO3 encoding two transcription factors belonging to the Forkhead family previously implicated in prostate carcinogenesis. Tumor-rich regions also contained mutations in genes frequently mutated in prostate cancer, including FOXA1, LRP1B, SPOP, and SPTA1. Our study reveals that SCNAs are widespread in both normal and tumor regions across the prostate gland of patients with localized prostate cancer and suggests that a subset of pseudo-diploid cells harboring chromosomal deletions that result in the loss of specific tumor-suppressor genes drive tumorigenesis in the aging prostate.

cancer biology↗

bioRxiv2023

Top-down Proteomics of 10,000 Single Brain Cells

We introduce single-cell Proteoform imaging Mass Spectrometry (scPiMS), which realizes the benefit of direct analysis of intact proteins to process 10,836 single cells from the rat hippocampus. This new platform addresses the throughput bottleneck for single cell proteomics using mass spectrometry, boosting cell processing rates by >20-fold in the field. We identified 169 proteoforms <70 kDa from single brain cells and classified 2758 of them as neurons, astrocytes or microglia cell types.

biochemistry↗

bioRxiv2023

Apolipoprotein B and Interleukin 1 Receptor Antagonist: Reversing the Risk of Coronary Heart Disease

BackgroundEpidemiological evidence for the link of interleukin 1 (IL-1) and its inhibition with coronary heart disease (CHD) remains controversial. We aim to investigate the cardiovascular effects of IL-1 receptor antagonist (IL-1Ra) and underlying mechanisms, as well as the potential interaction with lifestyle factors. MethodsA comprehensive multivariable Mendelian randomization study was performed. Genetic variants identified from a genome-wide association study involving 30,931 individuals were used as instrumental variables for the serum IL-1Ra concentrations. Genetic associations with CHD (60,801 cases and 123,504 controls) were extracted from the CARDIoGRAMplusC4D consortium. Inverse-variance weighted method was utilized to derive effect estimates, while supplementary analyses employing various statistical approaches. ResultsGenetically determined IL-1Ra level was associated with increased risk of CHD (odds ratio (OR), 1.07; 95% CI: 1.03-1.17) and myocardial infarction (OR, 1.13; 95% CI: 1.04-1.21). The main results remained consistent in supplementary analyses. Besides, IL-1Ra was associated with circulating levels of various lipoprotein lipids, apolipoproteins and fasting glucose. Interestingly, observed association pattern with CHD was reversed when adjusting for apolipoprotein B (OR, 0.84; 95%CI: 0.71-0.99) and slightly attenuated on accounting for other cardiometabolic risk factors. Appropriate lifestyle intervention was found to lower IL-1Ra concentration and mitigate the heightened CHD risk it posed. ConclusionsApolipoprotein B represents the key driver, and a potential target for reversal of the causal link between serum IL-1Ra and increased risk of CHD/MI. The combined therapy involving IL-1 inhibition and lipid-modifying treatment aimed at apolipoprotein B merit further exploration.

genetics↗

bioRxiv2022

Concurrent measurement of perfusion parameters related to small blood and lymphatic vessels in the human brain using dynamic dual-spin-echo perfusion (DDSEP) MRI

PURPOSEAccumulating evidence from recent studies has indicated the importance of studying the interaction between the microvascular and lymphatic systems in the brain. To date, most imaging methods can only measure blood or lymphatic vessels separately, such as dynamic-susceptibility-contrast (DSC) MRI for blood vessels and DSC MRI in the CSF (cDSC MRI) for lymphatic vessels. An approach that can measure both blood and lymphatic vessels in a single scan will offer the advantages such as halved scan time and contrast dosage. Based on previous works on DSC and cDSC MRI, this study proposes an MRI approach for concurrent measurement of perfusion parameters related to small blood and lymphatic vessels in the brain within one single scan. METHODSBloch simulations were performed to optimize a dual-echo sequence for the measurement of gadolinium(Gd)-induced blood and CSF signal changes using a short and a long echo time, respectively. MRI experiments were performed in healthy subjects to evaluate the dual-echo approach by comparing it with existing separate methods. RESULTSThe proposed method showed consistent results in human brains as previous studies using separate methods. Signal changes from small blood vessels occurred faster than lymphatic vessels after intravenous Gd-injection. CONCLUSIONGd-induced signal changes in blood and CSF can be detected simultaneously in healthy subjects with the proposed sequence. To the best of our knowledge, this may be the first study in which the temporal difference in Gd-induced signal changes from small blood and lymphatic vessels after intravenous Gd-injection was measured in the same human subjects.

neuroscience↗

bioRxiv2022

Ethylene augments root hypoxia tolerance through amelioration of reactive oxygen species and growth cessation

Flooded plants experience impaired gas diffusion underwater, leading to oxygen deprivation (hypoxia). The volatile plant hormone ethylene is rapidly trapped in submerged plant cells and is instrumental for enhanced hypoxia acclimation. However, the precise mechanisms underpinning ethylene-enhanced hypoxia survival remain unclear. We studied the effect of ethylene pre-treatment on hypoxia survival of primary Arabidopsis thaliana root tips. Both hypoxia itself and re-oxygenation following hypoxia are highly damaging to root tip cells and ethylene pre-treatments reduced this damage. Ethylene pre-treatment alone altered the abundance of transcripts and proteins involved in hypoxia responses, root growth, translation and reactive oxygen species (ROS) homeostasis. Through imaging and manipulating ROS abundance in planta, we demonstrate that ethylene limits excessive ROS formation during hypoxia and subsequent re-oxygenation and improves oxidative stress survival. In addition, we show that ethylene leads to rapid root growth cessation and this quiescence behaviour contributes to enhanced hypoxia tolerance. Collectively, our results show that the early flooding signal ethylene modulates a variety of processes that all contribute to hypoxia survival.

plant biology↗

bioRxiv2021

Escape Steering by Cholecystokinin Peptidergic Signaling

Escape is an evolutionarily conserved and essential avoidance response. Considered to be innate, most studies on escape responses focused on hard-wired circuits. We report here that peptidergic signaling is an integral and necessary component of the Caenorhabditis elegans escape circuit. Combining genetic screening, electrophysiology and calcium imaging, we reveal that a neuropeptide NLP-18 and its cholecystokinin receptor CKR-1 enable the escape circuit to execute a full omega ({Omega}) turn, the last motor step where the animal robustly steers away from its original trajectory. We demonstrate in vivo and in vitro that CKR-1 is a Gq protein coupled receptor for NLP-18. in vivo, NLP-18 is mainly secreted by the gustatory sensory neuron (ASI) to activate CKR-1 in the head motor neuron (SMD) and the turn-initiating interneuron (AIB). Removal of NLP-18, removal of CKR-1, or specific knockdown of CKR-1 in SMD or AIB neurons lead to shallower turns hence less robust escape steering. Consistently, elevation of head motor neuron (SMD)s Ca2+ transients during escape steering is attenuated upon the removal of NLP-18 or CKR-1. in vitro, synthetic NLP-18 directly evokes CKR-1-dependent currents in oocytes and CKR-1-dependent Ca2+ transients in SMD. Thus, cholecystokinin signaling modulates an escape circuit to generate robust escape steering.

neuroscience↗

bioRxiv2021

Direct Imaging and Identification of Proteoforms up to 70 kDa from Human Tissue

Imaging of proteoforms in human tissues is hindered by low molecular specificity and limited proteome coverage. Here, we introduce proteoform imaging mass spectrometry (PiMS), which increases the size limit for proteoform detection and identification by 4-fold compared to reported methods, and reveals tissue localization of proteoforms at <80 m spatial resolution. PiMS advances proteoform imaging by combining ambient nanospray desorption electrospray ionization (nano-DESI) with ion detection using individual ion mass spectrometry (I2MS). We demonstrate the first proteoform imaging of human kidney, identifying 169 of 400 proteoforms <70 kDa using top-down mass spectrometry and database lookup from the human proteoform atlas, including dozens of key enzymes in primary metabolism. PiMS images reveal distinct spatial localizations of proteoforms to both anatomical structures and cellular neighborhoods in the vasculature, medulla, and cortex regions of the human kidney. The benefits of PiMS are poised to increase proteome coverage for label-free protein imaging of tissues. TeaserNano-DESI combined with individual ion mass spectrometry generates images of proteoforms up to 70 kDa.

biochemistry↗

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↗