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Tang, M.

Publications and source records attributed to Tang, M..

At least 19 recordsLinked to original sources

scRBP infers cell-specific RNA-binding protein regulons from single-cell transcriptomes at gene and isoform resolution

Single-cell regulatory network inference remains dominated by transcription factors, despite RNA-binding proteins (RBPs) orchestrating major aspects of transcriptional regulation. We present scRBP, a framework that infers motif-supported RBP regulons from short- and long-read single-cell transcriptomes at gene and isoform resolution, resolves targets by transcript region (5'UTR, CDS, intron, 3'UTR), scores regulon activity in individual cells, and tests common- and rare-variant association against matched empirical nulls. From 20,746 motifs for 616 RBPs, scRBP recovered experimentally defined targets across 223 ENCODE eCLIP datasets at gene and isoform level. Across 30 tissues, transcript-region preferences separated 3'UTR-associated stability factors from intron-dominant splicing regulators. In published genome-scale CRISPRi Perturb-seq data, scRBP-inferred targets were over-represented among genes responding to RBP knockdown (1.4-2.5-fold across 161 RBPs; FDR<2x10-4). Across 6.2 million cells and 50 traits, scRBP prioritized cell-specific post-transcriptional programs linking human genetic risk to development and disease.

genetics↗

Cryptosporidium sex employs a complex male fertilization apparatus that is required for continued infection

Most apicomplexan parasites replicate asexually to colonize their mammalian hosts, and sexually in the context of transmission. In contrast, for Cryptosporidium sex is essential to sustain intestinal infection in vivo and therefore is a promising opportunity to prevent and treat the disease. However, the mechanism of sex, which occurs within host enterocytes, is poorly understood, limiting the discovery of targets for such intervention. Here we identify an elaborate fertilization apparatus and numerous of its molecular components in male gametes. We discern two elements, one displayed on the apex, that makes intimate contact with host cells containing female parasites, and a second internal structure, that harbors the membrane fusogen HAP2. Ablation of HAP2 by conditional mutagenesis blocked fertilization and oocyst production, rapidly cured infected mice and left them with enhanced resistance to subsequent challenge. Our studies provide insights into a remarkable fertilization mechanism and highlight specific molecules as targets for translation.

microbiology↗

Non-canonical IL-2 signaling facilitates peripheral regulatory T cell differentiation

Non-canonical IL-2 signaling, termed Monoclonal antibody or Matrix-directed Alternative Cytokine Signaling (MACS), is mediated by a CD25-chemokine receptor complex and operates in concert with the canonical JAK-STAT5 pathway; however, its role in T cell homeostasis remains poorly defined. Here, we uncover a role for MACS in regulatory T cell (Treg) differentiation and functional specification. We generated Il2E66K/E66K mice in which CD25-CCR7 assembly is disrupted and IL-2-induced STAT5 phosphorylation is preserved. Immunophenotyping analysis by flow cytometry revealed that MACS deficiency reduces the accumulation of Nrp1- Foxp3+ Tregs in gut-associated lymphoid tissues from 24-weeks-old Il2E66K/E66K mutant mice. Single-cell transcriptomics, functional suppression assays, and in vitro differentiation revealed that MACS engagement drives Treg differentiation and sustains effector Treg programs - marked by robust IL-10 expression - in part via an AP-1-dependent transcriptional network. These findings establish IL-2 MACS as a distinct signal directing peripheral immune tolerance and highlight a potential node for targeted immunomodulation.

immunology↗

Refinement of the Pathogenic T Cell Receptor Motif Suggests Type 17 CD8+ T Cells Initiate HLA-B*27-associated Autoimmunity

Human leukocyte antigen B*27 (HLA-B*27) is a major risk factor for autoimmune diseases such as axial spondyloarthritis (axSpA), acute anterior uveitis (AAU), and psoriatic arthritis (PsA). HLA-B*27 presents bacterial and self-antigens to disease-associated CD8+ T cells, however, how this leads to a pathogenic IL-17-mediated disease remains unclear. We performed mutational experiments in an established disease-associated TCR and demonstrated that the pathogenic motif encompasses a wider range of TCR sequences than previously appreciated. We next leveraged computational pairing of alpha/beta TCR sequencing (TCR-seq) to demonstrate that the broadened pathogenic motif distinguishes axSpA and AAU patients from healthy controls. Paired single-cell RNA sequencing and single-cell TCR sequencing datasets demonstrated that the pathogenic cells have a distinct transcriptional signature. We find a coupling of pathogenic TCRs to this transcriptional signature in public datasets from axSpA and PsA joint fluid and AAU ocular fluid. Finally, we detect the pathogenic CD8+ T cells in the gut and demonstrate that they express a Type 17 program. Our findings suggest that HLA-B*27+ axSpA, AAU, and PsA are initiated by HLA-B*27-restricted pathogenic CD8+ T cells that undergo Type 17 differentiation in response to intestinal antigens.

immunology↗

Autism genes converge on three functional programs organized by neuronal subclass, developmental timing, and cortical patterning

Our companion sequencing study uncovered 253 genes robustly associated with autism spectrum disorder (ASD), yet the biological programs they impact, and the cellular, developmental, and spatial contexts in which they converge, remain unresolved. Here we systematically contextualize genes associated with ASD across neurodevelopment and cortical areas, integrating developmental single-cell and spatial atlases with gene- and isoform co-expression, regulatory, proteomic, and synaptic networks. Genetic burden concentrates within temporally-resolved neuronal subclasses: newborn excitatory neurons, immature interneurons, and maturing intratelencephalic lineages. Genes associated with ASD converge on three functional programs--gene regulation, neuronal morphogenesis, and synaptic transmembrane signaling machinery--resolved from 28 ASD-associated networks, several of which are directly regulated by ASD genes including MEF2C, SOX11, and FOXP2. These programs are spatially patterned, with risk genes exhibiting an increasing anterior-to-posterior cortical expression gradient, anchored in the primary visual cortex and driven by excitatory neuron gene-regulatory programs. Finally, ASD risk genes associated with more severe developmental phenotypes show broader excitatory neuron enrichment and less interneuron involvement. Together, these findings anchor ASD genetic vulnerability to specific neurodevelopmental lineages, epochs, and molecular substrates, and delineate the features that distinguish ASD from comorbidities with broader developmental impacts.

genomics↗

Transcriptomic analysis of human induced pluripotent stem cell cardiomyocytes and myocardial tissue reveals novel role for miR-9-5p in hypertrophic cardiomyopathy

Hypertrophic cardiomyopathy (HCM) is an inherited disease characterized by the thickening of the heart muscle. Mutations in genes encoding contractile proteins, such MYBPC3 and MYH7 account for over half of patients with familial HCM. MicroRNAs (miRNAs) are pivotal regulators of gene expression that may influence disease progression. Despite their potential significance, there is a scarcity of published data on miRNAs in HCM. Induced pluripotent stem cells (iPSCs) have emerged as valuable tools for modeling various cardiovascular diseases, including HCM. However, the miRNA expression profiles associated with HCM remain largely unexplored within iPSC models. Investigating the differential expression of miRNAs in HCM patients offers a promising avenue to identify potential therapeutic targets for individuals affected by this condition. In this study, we performed an unbiased screen using a microarray (NanoString Technologies) that contained 798 miRNAs to identify differentially expressed miRNAs in iPSC-cardiomyocytes (CM) and myocardial tissues derived from healthy donors and HCM patients with MYBPC3 and MYH7 mutations, identifying miR-9-5p as significantly downregulated in all HCM iPSC-CM and myectomy tissue compared to control. KEGG pathway analysis of gene targets using miRTarBase and g:Profiler revealed that miR-9-5p regulates genes in the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor resistance pathway, which is involved in hypercontractility associated with HCM. Modulation of miR-9-5p expression in vitro using mimics significantly reduced cardiomyocyte size and contractility of MYBPC3 mutant iPSC-CMs whereas healthy control iPSC-CMs treated with antagomiRs exhibited hypertrophy. Our findings identify miR-9-5p as a regulator of cardiomyocyte hypertrophy and contractility, and suggest the miR-9-5p/EGFR tyrosine kinase inhibitor resistance axis as a potential therapeutic target to mitigate hypertrophy and hypercontractility exhibited in HCM.

molecular biology↗

A direct, MFRN-independent Fe(II) transfer pathway at mitochondria-lysosome contacts

Mitochondrial iron homeostasis is fundamental to respiration and redox balance, and its dysregulation is implicated in neurodegeneration, cardiomyopathy, and metabolic diseases. Although lysosomes harbor the major cellular iron reservoir, the prevailing model holds that mitochondria acquire Fe(II) directly from the cytosolic labile iron pool (LIP) via MFRN transporters. Here, we challenge the canonical view by identifying a direct, MFRN-independent Fe(II) transfer pathway at mitochondria-lysosome contacts (MLCs). This VPS39/TOMM22/SFXN1-coordinated pathway enables lysosome-to-mitochondria Fe(II) flux bypassing the cytosolic LIP. Using live-cell structured illumination microscopy (SIM), we visualize direct Fe(II) transfer specifically occurring at MLCs. Multiple lines of evidence confirm that VPS39 and TOMM22 stabilize MLCs, while SFXN1 serves as the core effector protein for this MLC-dependent Fe(II) transport. Notably, SFXN1 knockdown markedly reduces mitochondrial Fe(II) levels independent of its established serine transport function. This pathway reveals a major route for mitochondrial Fe(II) acquisition to support redox homeostasis.

cell biology↗

Chromatin Landscape of Cancer Cell Lines Identifies Enhancer Subtypes

Epigenetic aberrations are a hallmark of cancer; however, systematic chromatin state maps of cancer cells are unavailable. We generated and analyzed 803 histone mark profiles in 142 cancer cell lines and 114 human tumors belonging to 9 solid tumor types. Irrespective of their cell-of-origin, cancer cells segregate from normal tissues based on their enhancer patterns, suggesting enhancer deregulation is a fundamental epigenetic feature in cancer. Enhancer based clustering defined 5 distinct subgroups of cancer cells (EpiC1-5) with unique developmental trajectories, molecular features and dependencies. Importantly, we define a set of core TFs that are critical for EpiC-specific enhancer patterns and survival. Notably, EpiC4 represented a predominantly epigenetic, pan-cancer subtype that displays poor survival, activation and dependence on a FN1-CAV1-SRC-PI3K-AKT signaling network. Together, these data uncover enhancer heterogeneity in pan-cancer systems with identification of a novel enhancer-based subtype and identify potential new therapeutic targets associated with unique epigenetic features.

cancer biology↗

FXR-mediated recruitment of PPP1CB suppresses SMAD2/3 phosphorylation to mitigate pulmonary fibrosis

Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal interstitial lung disease with limited treatment options and poorly understood molecular underpinnings. Dysregulated TGF-{beta}/SMAD signaling is a key driver of fibrotic remodeling, promoting persistent myofibroblast activation and excessive extracellular matrix deposition. Here we identify the Farnesoid X receptor (FXR), a bile acid activated nuclear receptor, as a previously unrecognized suppressor of pulmonary fibrosis. FXR expression is significantly reduced in lung tissues from patients with PF and in myofibroblasts derived from BLM-induced mouse models, correlating inversely with fibrosis severity. Genetic ablation of FXR exacerbates BLM-induced pulmonary fibrosis by promoting fibroblast hyperactivation and dysregulation of the TGF-{beta}/SMAD signaling pathway. Mechanistically, we identify PPP1CB as a previously unrecognized FXR-interacting protein in primary myofibroblasts derived from IPF patients. We further show that FXR both increases chromatin accessibility at the PPP1CB locus and assembles a functional complex with PPP1CB, which in turn promotes SMAD2/3 dephosphorylation and suppresses their nuclear translocation. Notably, the clinical-stage FXR agonist TERN101 exhibits potent therapeutic efficacy in a BLM-induced mouse pulmonary fibrosis model. These findings establish FXR as a critical antifibrotic regulator in lung tissue and suggest that pharmacological activation of FXR may offer a promising therapeutic strategy for IPF.

cell biology↗

A novel AR molecular glue degrader via bivalent engagement of the N-terminal domain and RNF213-UBE2J2 complex

Targeted protein degradation enables the elimination of disease-relevant proteins through induced proximity between E3 ligases and substrates. Current androgen receptor (AR) therapies act via the ligand-binding domain (LBD) but fail against constitutively active LBD mutants or splice variants such as AR-V7. Here, we identify GZL626, a small-molecule degrader that induces proteasome-dependent degradation of both full-length AR and AR-V7. GZL626 suppresses AR transcriptional activity, inhibits proliferation of AR-positive prostate cancer cells, and blocks SARS-CoV-2 infection. Mechanistically, GZL626 binds the intrinsically disordered AR N-terminal domain (NTD) and promotes formation of a noncanonical RNF213-UBE2J2-AR ternary complex that drives AR ubiquitination and degradation. The AR DNA-binding domain (DBD) acts as a structural hub within this assembly. Distinct from PROTACs or classical molecular glues, GZL626 engages both AR and RNF213 bivalently, remodeling protein interactions to stabilize a functional E3-E2-substrate complex. These findings establish GZL626 as a first-in-class NTD degrader with potential to overcome resistance in advanced prostate cancer.

biophysics↗

Learning complex temporal dependencies via local synaptic plasticity

The ability to extract and exploit temporal structure across diverse tasks is central to human cognition. Neuroscientists have typically relied on recurrent neural networks (RNNs) trained with backpropagation through time (BPTT) when modelling neural and behavioural processes such as decision-making and motor control. However, this algorithm has limited biological plausibility, hence the computational principles underlying efficient learning of temporal dependencies remain unresolved. Here, we investigate temporal predictive coding (tPC), a recently proposed framework that extends predictive coding to the temporal domain while preserving local Hebbian update rules. We analyse and extend tPC to establish its relationship with several influential computational models of learning in RNNs, including BPTT, reservoir computing, and eligibility propagation (e-prop). We first demonstrate a functional equivalence between tPC and tBPTT1, a variant of BPTT in which gradients are propagated only one time step into the past. We then show that tPC can leverage reservoir dynamics to encode short-range temporal context, and simultaneously sculpt neural trajectories in state space to support downstream readout. We further demonstrate that hierarchical recurrent dynamics can facilitate learning of more complex temporal dependencies, while additionally conferring robustness to strong distractors. Finally, we show that tPC networks can be augmented with biologically inspired eligibility traces to solve temporally extended context-dependent tasks. Together, these results reveal that relatively simple recurrent networks governed by local plasticity can support temporal learning in more complex settings than previously appreciated. Author summaryTo navigate the world, our brains must constantly track how events unfold over time, whether we are predicting the next word in a sentence or timing a tennis swing. Neuroscientists often use artificial neural networks to study how the brain learns these sequences. However, these models are often not biologically realistic, since they adjust neuronal connections using information that individual neurons would not have access to in the brain. Here, we examine an alternative framework called temporal predictive coding, which is designed to better reflect how brain networks may be organised. We show that these biologically inspired networks are surprisingly powerful: they can remember recent context and, when arranged in layers, can learn increasingly complex patterns. We also show that they work better when equipped with a memory-like mechanism that helps neurons link recent events across time. Overall, our findings suggest that relatively simple, biologically inspired networks may capture how we process sequential events better than previously thought.

neuroscience↗

ROS Impair Mitophagy via PARylation of PINK1

Mitophagy is the process of selective autophagic clearance of damaged mitochondria and is closely implicated in neurodegenerative disease. PTEN-induced kinase 1 (PINK1) and a RBR E3 ubiquitin-protein ligase (Parkin) constitute a positive feedback loop in mitophagy initiation. It is known that reactive oxygen species (ROS) modulate mitophagy, while the exact regulatory mechanism remains largely elusive. Here, we found that exogenously applied ROS effectively block mitophagy induced by acute mitochondrial damage agents, which could be reversed by antioxidants. Mechanistically, ROS activate poly(ADP-ribose) polymerase 1 (PARP1), and suppression of PARP1 eliminates the inhibitory effect of ROS on mitophagy. Notably, PARP1 directly interacts with PINK1 and mediates its PARylation at residue E417, thereby negatively regulating PINK1 function. Collectively, our study identifies PARylation as a new form of post-translational modification of PINK1 and reveals a novel mechanism underlying the regulatory role of ROS in mitophagy by PARP1 activation and PARylation of PINK1. In briefGao et al. demonstrate that exogenous ROS inhibit mitophagy. Mechanistically, ROS activate PARP1, which mediates PARylation of PINK1, a central regulator of mitophagy, leading to its functional impairment. This study reveals a novel regulatory mechanism of ROS on mitophagy through PARP1 activation and identifies PARylation as a novel form of post-translational modification of PINK1. HighlightsO_LIROS block PINK1-Parkin-mediated mitophagy. C_LIO_LIROS activate PARP1. C_LIO_LIPARP1 suppression eliminates the inhibitory effect of ROS on mitophagy. C_LIO_LIPARylation of PINK1 by PARP1 impairs its activity and mitophagy. C_LI

Cell Biology↗

A Sandwich-Structured Silk Fibroin Mesh with ROS-Responsive and Immunoregulatory Functions for Pelvic Floor Repair

Current biodegradable meshes for pelvic floor repair are constrained by a limited ability to actively modulate the hostile immune microenvironment following implantation. To address these challenges, we developed a functionalized degradable silk fibroin mesh (SFM) integrated with a reactive oxygen species (ROS)-responsive nanocomposite hydrogel. The resulting composite mesh, SFM@Gel-NP, features a "hydrogel-mesh-hydrogel" sandwich structure, wherein the hydrogel layers are loaded with self-assembled nanoparticles (NP-H-CRFP) for the co-delivery of the STING inhibitor H-151 and the ROS-scavenging agent catechin. This design provides immediate mechanical reinforcement while enabling microenvironment-triggered drug release. In vitro, NP-H-CRFP demonstrated efficient cellular uptake, significant ROS clearance, and effective attenuation of macrophage inflammation and apoptosis. In vivo, SFM@Gel-NP remodeled the local immune milieu by inhibiting the ROS/cGAS-STING/NF-{kappa}B axis, thereby promoting a shift from pro-inflammatory M1 toward pro-regenerative M2 macrophage polarization. This immunomodulatory effect, coupled with enhanced and well-organized collagen deposition--particularly of early type III collagen--resulted in improved tissue integration and repair. This work presents a novel strategy that combines structural reinforcement with active immune regulation, offering a promising next-generation solution for durable and functional pelvic floor reconstruction.

bioengineering↗

IgA Targeting in the Infant Gut Is Modulated by Diet and Increasingly Directed Towards Persistent Species

BackgroundIgA is the dominant antibody in the human gut and a key regulator of host-microbe interactions. Infants begin to produce IgA at around 6 months old and receive large quantities of IgA via human milk, but technical limitations have prevented species-level characterization of IgA binding in early life. This has left basic knowledge gaps about which species are targeted by IgA in infancy, and how modifiable lifestyle factors like breastfeeding and complementary feeding impact IgA targeting. ResultsHere we adapt Metagenomic Immunoglobulin Sequencing (MIg-Seq) for low-biomass infant fecal samples and apply this optimized protocol to 32 longitudinal samples from 16 infants enrolled in the MINT trial, a four-arm randomized controlled trial comparing meat-based, dairy-based, plant-based, and reference complementary feeding patterns, with fecal sampling at 6 and 12 months (pre and post intervention). Infant IgA targeting mirrors adults at the phylum level, with both age groups showing significantly higher IgA targeting of Pseudomonadota and lower targeting of Bacteroidota relative to other phyla. During the substantial microbiome compositional shifts noted between 6 and 12 months, IgA targeting is significantly more stable than the microbiome itself. Among persistent colonizers, IgA targeting strengthens significantly from 6 to 12 months, with the most pronounced effect observed for Bifidobacterium, a finding robust across all dietary arms and feeding modes. The feeding arm to which infants were enrolled was not significantly associated with IgA binding, but several nutrient-specific associations were discovered. Animal-derived nutrients, particularly cholesterol, are strongly positively correlated with IgA targeting of Bifidobacterium longum, while plant-derived carotenoids are positively associated with IgA targeting of Flavonifractor plautii and Ruminococcus gnavus. ConclusionsThis study introduces an experimental and computational framework for species-level IgA profiling in the infant gut. The progressive strengthening of IgA targeting of Bifidobacterium and other beneficial persistent colonizers suggests a role for IgA in reinforcing beneficial microbes during infancy. The nutrient-specific dietary effects on IgA targeting reveal the immunological consequences of the complementary feeding period, and highlight a contrast between animal-versus plant-based diets. Together, these findings point to early nutritional interventions and IgA-based therapeutics as promising tools for promoting healthy immune-microbiome development.

microbiology↗

AM-DMF-SCP-pro: An Ultrafast and Streamlined Nanolitre-Scale Lab-on-a-Chip Platform for Single-Cell Proteomics and Tumor Microenvironment Profiling

Single-cell proteomics (SCP) remains constrained by slow sample preparation and background interference in low-input, multistep workflows, limiting its broader practical use in complex biological samples. Here we report AM-DMF-SCP-pro, a streamlined active-matrix digital microfluidic workflow that enables rapid on-chip lysis and digestion in 6 nL droplets within a closed nanolitre-confined microenvironment. AM-DMF-SCP-pro reduces total sample-preparation time to as little as 30 min, including a 15 min digestion step, while maintaining quantitative reproducibility and digestion performance. Systematic optimization of mass spectrometry acquisition and nanolitre-scale digestion conditions enables deeper, more sensitive and lower-background proteome profiling from ultra-low peptide inputs. In murine tumor samples, AM-DMF-SCP-pro reliably resolves immune and tumor compartments, identifies treatment-associated tumor cell states and enables quantitative analysis of neutrophil-associated proteomic signatures. These results establish AM-DMF-SCP-pro as a practical workflow for rapid, low-background single-cell proteome profiling in complex biological samples.

systems biology↗

Physics-informed self-supervised learning enables spectra-free multiplexed imaging on standard fluorescence microscopes

Multiplexed fluorescence imaging is limited by spectral overlap and the small number of excitation or emission channels available on standard microscopes, restricting most laboratories to low-plex imaging. Here we introduce physics-informed spectra-free multiplexed imaging (PhySMI), a self-supervised framework for underdetermined spectral unmixing that enables highly multiplexed imaging without dense spectral measurements after training. By embedding the spectral forward-mixing process into a self-consistent architecture, PhySMI recovers physically plausible source decompositions from unlabeled data without paired ground-truth labels while suppressing stochastic acquisition noise. PhySMI resolves five subcellular structures from only three excitation channels, overcoming the conventional channel-number limit while preserving spectral fidelity and minimizing crosstalk (<0.5%). The framework also generalizes across imaging systems, enabling zero-shot deployment on standard fluorescence microscopes. In live cells, PhySMI enables fast five-color imaging of dynamic multi-organelle interactions with improved temporal resolution and reduced photobleaching and phototoxicity relative to conventional spectral imaging. These results establish a general strategy for physics-informed learning in underdetermined imaging inverse problems and represent a step toward a general-purpose framework for highly multiplexed fluorescence imaging on standard microscopy platforms.

biophysics↗

Identification of a neural circuit that enables safe, long-term torpor in mice

Torpor, a state of regulated hypothermia and hypometabolism, is a critical survival strategy in certain mammals. Previous studies established the primacy of neuron control in initiating acute torpor. However, whether neuromodulation can safely sustain torpor over the long term, and the specific governing pathways, remain unanswered challenges limiting its translational potential. Here we identify a distinct preoptic neuronal population expressing General control nonderepressible 2 ( G neurons) in mice that is essential and sufficient for torpor induction. Strikingly, sustained and selective activation of G neurons induces a stable, weeks-long torpid state (G neuron-driven long-term torpor, GLT), from which animals arouse without obvious behavioral deficits or tissue pathology. In contrast, long-term torpor driven by pan-neuronal activation of the same brain region (PLT) causes multiple post-recovery damages, underscoring the unique safety profile of selective pathway of G neurons. In a mouse cancer model, GLT directly suppressed tumor proliferation and markedly sensitized tumors to chemotherapy, achieving profound therapeutic outcomes. Together, we delineate a distinct neuronal population safely enabling prolonged torpor. This establishes a specific paradigm for inducing a stable and sustained hypometabolic state, providing a transformative platform for fundamental physiological research and pioneering clinical strategies against chronic pathologies such as cancer.

neuroscience↗

The tongue-brain axis mediates a hidden amino acid appetite

Selecting a diet containing all essential amino acids (EAAs) is critical for health. Following EAA deprivation, animals can select a nutritiously complete food source; however, the underlying mechanisms in vertebrates remain unclear. In mice, we show that leucine deficiency activates hypothalamic agouti-related protein (AgRP) neurons, which project to the paraventricular thalamus (PVT) via {gamma}-aminobutyric acid and are required for EAA deficiency-induced leucine appetite in mice. Furthermore, the peripheral tongue amino acid sensor general control nonderepressive-2 (GCN2) mediates acute EAA appetite via AgRP neurons. Together, these findings identify a tongue-AgRP-PVT circuit underlying EAA appetite, which is important for the rapid and accurate selection of essential nutrients.

neuroscience↗