Biology subjects

Hu, S.-Y.

Publications and source records attributed to Hu, S.-Y..

6 recordsLinked to original sources

bioRxiv2026

Gradual evolution of multiplexed spatial coding within a conserved hippocampal scaffold

The hippocampus constructs spatial maps for navigation, yet their format differs markedly across species. Whether divergences reflect ecological adaptation, phylogenetic architecture, or flexible coding strategy within a conserved circuit has been difficult to disentangle. We recorded CA1 in rats and tree shrews (Tupaia belangeri chinensis), a mammal phylogenetically and ecologically between rodents and primates, using identical tasks and analyses. Unlike the position-dominant code of rats, tree shrew CA1 exhibited a hybrid representation: weaker position selectivity, stronger non-positional tuning, and prevalent multiplexing approaching primate characteristics. Multiplexed populations decoded location as accurately as rat position populations while using fewer neurons, suggesting computational advantages of high-dimensional coding. Despite this representational shift, proximo-distal gradient, pattern completion, and global remapping persisted. Representational format can be tuned without altering the underlying circuit. Tree shrews occupy an evolutionary intermediate in which ancestral network dynamics are repurposed for efficient multiplexed coding, tracing a transition toward primate-like spatial representations.

neuroscience↗

bioRxiv2025

Dentate gyrus drives pattern separation in proximal CA3 during rate, but not global, remapping

The dentate gyrus (DG) transforms overlapping experiences into discrete memory traces, yet how DG output shapes population coding within the hippocampus remains unclear. We combined selective DG lesions with large-scale recordings across the CA3 proximo-distal axis as rats explored environments varying in contextual similarity. Global remapping in CA3 remained robust following DG lesion, whereas rate-based contextual coding was substantially attenuated, most strongly in proximal CA3 and attenuating distally, paralleling mossy-fiber topography. Granule cells and mossy cells additionally coded complementary aspects of local objects and mediated CA3 responses to object manipulation. These data causally link the enhanced rate coding of proximal CA3 to its preferential DG innervation and support a dual organization of contextual discrimination: categorical changes in environmental identity are signaled independently of the DG, whereas fine-grained discrimination is facilitated by DG-mediated rate modulation. By selectively amplifying rate-coded discrimination of subtle contextual differences, the DG sharpens the hippocampal network's capacity to resolve overlapping experiences into distinct representations.

neuroscience↗

bioRxiv2024

Comprehensive profiling of transcriptional regulation in cartilage reveals pathogenesis of osteoarthritis

Cartilage damage is a leading cause of osteoarthritis (OA) etiology, however, the underlying mechanism governing gene expression regulation in this progress is poorly understood. Here, we described a comprehensive profiling of transcriptional regulation of 235 primary human cartilage samples. We identified 3,352 independent significant expression quantitative trait loci (eQTLs) for 3,109 genes. We explored the candidate casual SNP and its underlying regulatory mechanism using our established functional fine-mapping pipeline by integrating the cartilage-specific ATAC-seq data. We identified 117 causal eQTLs that display allele-specific open chromatin (ASoC) and 547 transcription factor binding-disruption (TBD) eQTLs. We conducted cell type-interaction eQTL (ci-eQTL) analyses based on speculated chondrocyte subtype proportions and revealed the regulation relationship of 120 eQTL-gene pairs showed cell type dependency. Further, by integrating with genome-wide association studies (GWASs) data of OA, we nominated 43 candidate effector genes for OA risk loci. We verified that the T allele of the OA risk variant rs11750646 increased the AR binding affinity to an open chromatin region and promoted the expression of an OA-related gene PIK3R1. Altogether, our findings provide new insights into the unique regulatory landscape of cartilage and elucidate potential mechanisms underlying the OA pathogenesis.

genetics↗

bioRxiv2024

Ternary representation of contextual information along the CA1 transverse axis

Episodic memory refers to the recollection of personally experienced events anchored in spatial contexts. Salient objects within a navigation environment serve as both landmarks and event cues; however, the nuanced integration of these elements during episodic memory formation is not well understood. The mnemonic functions of the hippocampal CA1 region are partially organized along its transverse axis, with proximal and distal subregions preferentially processing spatial and non-spatial information, respectively. Based on comprehensive analysis of neuronal responses along the CA1 proximodistal axis to manipulations of environmental cues and object features, we identified an event-like population coding within CA1 following object displacement. In addition, the neuronal responses at both initial and relocated object locations were shaped by distinct convergent inputs. These findings highlight the specific roles that objects may play in spatial navigation and memory encoding, providing novel insights into the selective processing of object-related information within the entorhinal-hippocampal network. Significance StatementSalient objects within a navigation environment serve as both landmarks and event cues critical for episodic memory. However, the enigmatic contribution of objects to the "where" and "what" components of episodic memory remains poorly understood. Here we comprehensively analyzed the neuronal responses in the hippocampal CA1 region along its transverse axis, to manipulations of environmental cues and object features. Our results revealed an event-like population coding within CA1 following object displacement, suggesting a minimal landmark role these objects play during memory formation. This study provides novel insights into the selective and flexible processing of object-related information within the entorhinal-hippocampal network.

neuroscience↗

bioRxiv2022

Extensive RNA editing in tomato nuclear genes

MicroTom tomato has a short growth cycle and high transformation efficiency, and is a prospective model plant for studying organ development, metabolism, and plant-microbe interactions. Here, with a newly assembled reference genome for this tomato cultivar and abundant RNA-seq data derived from tissues of different organs/developmental stages/treatments, we constructed multiple gene co-expression networks, which will provide valuable clues for the identification of important genes involved in diverse regulatory pathways during plant growth, e.g., arbuscular mycorrhizal symbiosis and fruit development. Additionally, non-coding RNAs, including miRNAs, lncRNAs and circRNAs were also identified, together with their potential targets. Interacting networks between different types of non-coding RNAs (miRNA-lncRNA), and non-coding RNAs and genes (miRNA-mRNA and lncRNA-mRNA) were constructed as well. Our results and data will provide valuable information for the study of organ differentiation and development of this important fruit. Lastly, we established a database (http://eplant.njau.edu.cn/microTomBase/) with genomic and transcriptomic data, as well as details of gene co-expression and interacting networks on microTom, and this database should be of great value to those who wants to adopt microTom as a model plant for research.

genomics↗

bioRxiv2019

Lineage-Specific Epigenomic and Genomic Activation of the Oncogene HNF4A Promotes Gastrointestinal Adenocarcinomas

BackgroundsGastrointestinal adenocarcinomas (GIACs) of the tubular GI tract including esophagus, stomach, colon and rectum comprise most GI cancers and share a spectrum of genomic features. However, the unified epigenomic changes specific to GIACs are less well-characterized.We applied mathematical algorithms to large-scale DNA methylome and transcriptome profiles to reconstruct transcription factor (TF) networks using 907 GIAC samples from The Cancer Genome Atlas (TCGA). Complementary epigenomic technologies were performed to investigate HNF4A activation, including Circularized Chromosome Conformation Capture (4C), Chromatin immunoprecipitation (ChIP) sequencing, Whole Genome Bisulfite Sequencing (WGBS), and Assay for Transposase-Accessible Chromatin (ATAC) sequencing. In vitro and in vivo cellular phenotypical assays were conducted to study HNF4A functions.\n\nResultsWe identified a list of functionally hyperactive master regulator (MR)TFs shared across different GIACs. As the top candidate, HNF4A exhibited prominent genomic and epigenomic activation in a GIAC-specific manner. We further characterized a complex interplay between HNF4A promoter and three distal enhancer elements, which was coordinated by GIAC-specific MRTFs including ELF3, GATA4, GATA6 and KLF5. HNF4A also self-regulated its own promoter and enhancers. Functionally, HNF4A promoted cancer proliferation and survival by transcriptionally activating many downstream targets including HNF1A and factors of Interleukin signaling in a lineage-specific manner.\n\nConclusionWe use a large cohort of patient samples and an unbiased mathematical approach to highlight lineage-specific oncogenic MRTFs, which provide new insights into the GIAC-specific gene regulatory networks, and identify potential therapeutic strategies against these common cancers.

cancer biology↗