Biology subjects

Yue, F.

Publications and source records attributed to Yue, F..

At least 19 recordsLinked to original sources

bioRxiv2026

MRI-compatible 3D Soft Carbon Neural Interface Enabled by Versatile Depth-tunable Laser Drawing

Soft neural interfaces are designed to minimize mechanical mismatch with the brain. However, planar and recessed electrode sites remain locally decoupled from the curved and pulsating cortical surface, degrading the fidelity of neural sensing. Here, we report a 3D soft carbon electrode array, enabled by a depth-tunable laser drawing strategy. This laser-driven workflow achieves versatile fabrication of customizable 3D soft carbon neural interfaces, eliminating the reliance on conventional thin-film microfabrication processes. The fully silicone-based electrode structure realize device-scale conformality, and the 3D soft carbon sites promote a non-penetrating, intimate neural-electrode interface. The CNT-3D array combined superior in-vitro electrochemical and in-vivo recording performance compared with Au-2D and CNT-2D controls. Furthermore, in bilateral rabbit cortex implantation, CNT-3D array retained 80.4% of electrocorticography power after 4 months, versus 11.7% for CNT-2D control. Moreover, the 3D sensing sites significantly suppressed line-frequency harmonics and background noise interference. Subsequently, during magnetic resonance imaging, the CNT-3D array exhibits negligible implant-induced artifacts compared to the conventional Pt-Ir metal array. Overall, this work establishes a laser drawing strategy that extends neural interfaces from macro device-scale conformality to micro site-scale coupling, providing a technological pathway for practical and translational soft neurotechnology.

bioengineering↗

bioRxiv2026

POU2AF2/OCA-T1 coactivates POU2F2 and defines a lineage-specific dependency in diffuse large B-cell lymphoma

Lineage-restricted transcriptional programs establish cell identity and can create selective dependencies in cancer. Here, we identify POU2AF2, encoding the transcriptional co-activator OCA-T1, as a critical lineage-specific dependency in a subset of diffuse large B-cell lymphoma (DLBCL). Pan-cancer dependency analyses and patient cohorts reveal elevated POU2AF2 expression in genetically aggressive DLBCL, where its depletion markedly suppresses tumor growth in vitro and in vivo. Mechanistically, POU2AF2 cooperates with the B-cell lineage-defining transcription factor POU2F2 (OCT2) to activate lymphocyte activation gene programs through direct chromatin engagement, thereby sustaining malignant transcriptional networks. We further identified a key epigenetic regulatory axis composed of the lineage-specific transcription factor TCF3 and the histone methyltransferase SET1A-COMPASS that drives POU2AF2 expression downstream of B-cell receptor signaling. Single-cell transcriptomic analysis reveals that POU2AF2 marks and sustains an innate-like B1 B-cell population in vivo, a candidate cell of origin for lymphoma. Together, these findings define a lineage-restricted POU2AF2/POU2F2 transcriptional module, controlled by a TCF3/SET1A epigenetic network, that sustains both innate-like B-cell identity and malignant fitness in DLBCL. Our study uncovers a previously unrecognized lineage-specific transcriptional dependency and highlights POU2AF2 and its associated regulatory circuitry as potential therapeutic targets in aggressive B-cell malignancies.

cell biology↗

bioRxiv2026

Adipocyte Pten Inhibition Improves Metabolic Health Associated with Expanded Lipid Storage Capacity and Reduced Inflammation

Adipose tissue dysfunction drives obesity-associated insulin resistance, but whether expanding adipocyte lipid storage can improve metabolic health remains unclear. Here, we generated adipocyte-specific Pten knockout mice (PtenAKO) using Adipoq-Cre to determine how chronic Pten loss affects adipose tissue remodeling and systemic metabolism. PtenAKO mice exhibit increased adiposity and adipocyte hypertrophy under chow and high-fat diet feeding, yet showing lower blood glucose and insulin levels, enhanced insulin sensitivity, and reduced hepatic lipid accumulation during basal growth and diet-induced obesity without systemic metabolic deterioration. Despite lipid enrichment in brown adipose tissue, Pten-deficient adipocytes maintain UCP1 expression, OXPHOS protein abundance, and mitochondrial ultrastructure. Transcriptomic analysis of inguinal white adipose tissue reveals activation of adipogenesis, lipid metabolism, insulin response, oxidative phosphorylation, lipid storage, vascular and extracellular matrix pathways, together with suppression of immune and inflammatory programs. Mechanistically, Pten deficiency increases Cav1 expression, caveolae abundance, collagen expression, and extracellular matrix remodeling, suggesting coordinated structural adaptation to support adipocyte expansion. These findings demonstrate that adipocyte Pten deficiency promotes metabolically healthy adipose expansion by enhancing lipid storage capacity, preserving adipocyte function, and reducing inflammation.

physiology↗

bioRxiv2026

NRMLncR, a myocyte-enriched long non-coding RNA, enhances myogenesis in mouse

Myogenesis is a stepwise process encompassing myogenic progenitor proliferation, lineage commitment, differentiation, myocyte fusion, and myotube maturation, and it is orchestrated by myogenic regulatory factors (MRFs) together with signaling pathways that coordinate these transitions. Long noncoding RNAs (lncRNAs) have emerged as important regulators of muscle development and regeneration, yet how lncRNAs integrate with canonical signaling networks to shape myogenic progression remains incompletely defined. Here, we identify a novel myocyte-enriched, Notch-repressed myogenic lncRNA (NRMLncR, known as A930003A15Rik), as a previously uncharacterized regulator of mouse myogenesis. The expression of NRMLncR is robustly induced during primary myoblast activation and differentiation. Loss-of-function analyses show that knockdown of NRMLncR impairs myogenic differentiation, accompanied by reduced expression of key myogenic genes. In contrast, adenovirus-mediated overexpression of NRMLncR enhances myogenic differentiation in vitro and is associated with increased muscle fiber size in vivo. Mechanistically, MyoD and MyoG occupy the NRMLncR promoter and promote its transcription during myogenic differentiation. NRMLncR knockdown alerts the transcription of nearby genes, suggesting its function through a cis-regulatory mechanism. RNA pull-down assays further identify an interaction between NRMLncR and the RNA-binding protein CELF1. Together, these findings establish NRMLncR as a novel Notch-associated lncRNA that promotes myogenic differentiation and provide insight into lncRNA-dependent regulation of the myogenic program.

genetics↗

bioRxiv2025

Chondrolectin regulates the sublaminar localization and regenerative function of muscle satellite cells in mice

Skeletal muscle satellite cells (SCs) reside between the myofiber sarcolemma and basal lamina, where extracellular matrix (ECM) interactions are essential for their maintenance and regenerative function. Here, we identify chondrolectin (CHODL), a type I transmembrane protein with a C-type lectin domain, as a critical regulator of SC biology. Single-cell RNA-seq analysis reveals that Chodl is highly enriched in quiescent SCs but downregulated in proliferating myoblasts. Using conditional knockout models, we show that deletion of Chodl in embryonic myoblasts (ChodlMKO) or adult SCs (ChodlPKO) does not affect muscle development but markedly impairs regeneration in both young and aged mice. Chodl-deficient SCs exhibit reduced self-renewal, diminish proliferation, and impair differentiation, leading to defective myofiber repair. In silico network perturbation further predicts disruption of ECM-ligand interactions and Notch signaling, consistent with our observation that a significant fraction of SCs in ChodlPKOmice localize outside the basal lamina and undergo precocious activation. Together, these findings establish CHODL as a key determinant of SC niche localization and regenerative function, uncovering a previously unrecognized mechanism linking ECM interactions to muscle stem cell maintenance and repair.

developmental biology↗

bioRxiv2025

Hepatocyte FAM210A deficiency disrupts mitochondrial function and triggers juvenile steatosis with compensatory repair in adulthood

Mitochondrial dynamics are central to maintaining liver metabolic homeostasis, yet the mechanisms that safeguarding mitochondrial integrity during development and metabolic dysfunction remain poorly defined. Here, we identify Family with sequence similarity 210 member A (FAM210A) as a hepatocyte-enriched mitochondrial regulator essential for postnatal liver maturation. Hepatocyte-specific deletion of Fam210a (Fam210aHKO) in mice caused early growth restriction, reduced body and liver mass, and pronounced hepatic steatosis with glycogen depletion. These defects were accompanied by lower postprandial glucose levels in the fasted-refeeding state, impaired oxidative phosphorylation, reduced mtDNA content, and abnormal cristae architecture. Transcriptomic and proteomic profiling revealed broad suppression of fatty acid, sterol, and bile acid metabolism, with concomitant glutathione stress responses. Mechanistically, FAM210A deficiency disrupted the YME1L-OPA1 axis, driving excessive OPA1 cleavage and cristae destabilization. Strikingly, these juvenile defects were transient and resolved by adulthood, underpinned by enhanced hepatocyte proliferation and mitochondrial biogenesis, consistent with a compensatory stress-adaptive response via the activation of ISR signaling. Together, these findings uncover FAM210A as a developmental safeguard of mitochondrial remodeling in hepatocytes and indicate compensatory programs with therapeutic relevance for chronic liver disease.

physiology↗

bioRxiv2025

Fibro-Adipogenic Progenitors require autocrine IGF-I in homeostatic and regenerating skeletal muscle

Fibro-Adipogenic Progenitors (FAPs) are mesenchymal stem cells that are vital for muscle homeostasis and regeneration but produce fibrosis and intramuscular fat under pathological conditions. Insulin-like Growth Factor-I (IGF-I) is a key regulator of muscle repair, satellite cell activity, macrophage polarization, and extracellular matrix (ECM) remodeling. We generated inducible FAP-specific Igf1 deficient (FID) mice to determine the necessity of FAP IGF-I. After BaCl2 injury, FID mice exhibited impaired muscle regeneration, with fewer Pax7+ cells, increased macrophage accumulation, smaller fibers, reduced ECM, and depressed FAP proliferation. Following glycerol injury, FID muscles exhibited reduced adipocyte accumulation. Primary FAPs isolated from injured FID muscles had blunted growth, upregulation of immune-regulatory genes and downregulation of ECM and cell proliferation genes, with delayed responses to fibrogenic and to adipogenic media. FAP property alterations were already present in homeostatic muscle, indicated by scRNASeq, with decreased indices of protein translation and ECM production as well as increased markers of senescence, confirmed in vivo and in vitro. Overall, FAP IGF-I is a critical autocrine factor, with further paracrine consequences for muscle regenerative capacity.

molecular biology↗

bioRxiv2024

Epigenetic remodeling and 3D chromatin reorganization governed by NKX2-1 drive neuroendocrine prostate cancer

A significant number of castration-resistant prostate cancer (CRPC) evolve into a neuroendocrine (NE) subtype termed NEPC, leading to resistance to androgen receptor (AR) pathway inhibitors and poor clinical outcomes. Through Hi-C analyses of a panel of patient-derived xenograft tumors, here we report drastically different 3D chromatin architectures between NEPC and CRPC samples. Such chromatin re-organization was faithfully recapitulated in vitro on isogenic cells undergoing NE transformation (NET). Mechanistically, neural transcription factor (TF) NKX2-1 is selectively and highly expressed in NEPC tumors and is indispensable for NET across various models. NKX2-1 preferentially binds to gene promoters, but it interacts with chromatin-pioneering factors such as FOXA2 at enhancer elements through chromatin looping, further strengthening FOXA2 binding at NE enhancers. Conversely, FOXA2 mediates regional DNA demethylation, attributing to NE enhancer priming and inducing NKX2-1 expression, forming a feed-forward loop. Single-cell multiome analyses of isogenic cells over time-course NET cells identify individual cells amid luminal-to-NE transformation, exhibiting intermediate epigenetic and transcriptome states. Lastly, NKX2-1/FOXA2 interacts with, and recruits CBP/p300 proteins to activate NE enhancers, and pharmacological inhibitors of CBP/p300 effectively blunted NE gene expression and abolished NEPC tumor growth. Thus, our study reports a hierarchical network of TFs governed by NKX2-1 in regulating the 2D and 3D chromatin re-organization during NET and uncovers a promising therapeutic approach to eradicate NEPC.

cancer biology↗

bioRxiv2024

PRC1 and CTCF-Mediated Transition from Poised to Active Chromatin Loops Drives Bivalent Gene Activation

Polycomb Repressive Complex 1 (PRC1) and CCCTC-binding factor (CTCF) are critical regulators of 3D chromatin architecture that influence cellular transcriptional programs. Spatial chromatin structures comprise conserved compartments, topologically associating domains (TADs), and dynamic, cell-type-specific chromatin loops. Although the role of CTCF in chromatin organization is well-known, the involvement of PRC1 is less understood. In this study, we identified an unexpected, essential role for the canonical Pcgf2-containing PRC1 complex (cPRC1.2), a known transcriptional repressor, in activating bivalent genes during differentiation. Our Hi-C analysis revealed that cPRC1.2 forms chromatin loops at bivalent promoters, rendering them silent yet poised for activation. Using mouse embryonic stem cells (ESCs) with CRISPR/Cas9-mediated gene editing, we found that the loss of Pcgf2, though not affecting the global level of H2AK119ub1, disrupts these cPRC1.2 loops in ESCs and impairs the transcriptional induction of crucial target genes necessary for neuronal differentiation. Furthermore, we identified CTCF enrichment at cPRC1.2 loop anchors and at Polycomb group (PcG) bodies, nuclear foci with concentrated PRC1 and its tethered chromatin domains, suggesting that PRC1 and CTCF cooperatively shape chromatin loop structures. Through virtual 4C and other genomic analyses, we discovered that establishing neuronal progenitor cell (NPC) identity involves a switch from cPRC1.2-mediated chromatin loops to CTCF-mediated active loops, enabling the expression of critical lineage-specific factors. This study uncovers a novel mechanism by which pre-formed PRC1 and CTCF loops at lineage-specific genes maintain a poised state for subsequent gene activation, advancing our understanding of the role of chromatin architecture in controlling cell fate transitions.

genomics↗

bioRxiv2024

Critical roles of Ikaros and HDAC1 in regulation of heterochromatin and tumor suppression in T-cell acute lymphoblastic leukemia

The IKZF1 gene encodes IKAROS - a DNA binding protein that acts as a tumor suppressor in T-cell acute lymphoblastic leukemia (T-ALL). IKAROS can act as a transcriptional repressor via recruitment of histone deacetylase 1 (HDAC1) and chromatin remodeling, however the mechanisms through which Ikaros exerts its tumor suppressor function via heterochromatin in T-ALL are largely unknown. We studied human and mouse T-ALL using a loss-of-function and IKZF1 re-expression approach, along with primary human T-ALL, and normal human and mouse thymocytes to establish the role of Ikaros and HDAC1 in global regulation of facultative heterochromatin and transcriptional repression in T-ALL. Results identified novel Ikaros and HDAC1 functions in T-ALL: Both Ikaros and HDAC1 are essential for EZH2 histone methyltransferase activity and formation of facultative heterochromatin; recruitment of HDAC1 by Ikaros is critical for establishment of H3K27me3 histone modification and repression of active enhancers; and Ikaros-HDAC1 complexes promote formation and expansion of H3K27me3 Large Organized Chromatin lysine (K) domains (LOCKs) and Broad Genic Repression Domains (BGRDs) in T-ALL. Our results establish the central role of Ikaros and HDAC1 in activation of EZH2, global regulation of the facultative heterochromatin landscape, and silencing of active enhancers that regulate oncogene expression.

bioinformatics↗

bioRxiv2024

Downregulations of mRNA expressions in the EPAS1and EGLN1: Unraveling a genetic mechanism for high-altitude hypoxia adaptation in Sherpa highlanders

Sherpa highlanders exhibit unique hypoxia-tolerant traits, likely evolved through natural selection in response to high-altitude conditions. Previous research has implicated EPAS1 and EGLN1 in this adaptation, but their functional mechanisms remain unclear. This study aims to elucidate these mechanisms by exploring mRNA expressions of EPAS1 and EGLN1 in Sherpa highlanders. Field investigations enrolled 54 healthy Sherpa highlanders and 25 non-Sherpa lowlanders in Namche Bazaar (3,440 m) and Kathmandu (1,300 m), respectively. Venous blood was collected for erythropoietin (EPO) measurements, EPAS1 and EGLN1 mRNA expression analyses, and genotyping of single nucleotide polymorphisms (SNPs) rs13419896 and rs4953354 in EPAS1, as well as rs1435166 and rs2153364 SNPs in EGLN1. Comparative analyses were conducted on these elements between highlanders and lowlanders. Despite decreased SpO2 in Sherpa highlanders, EPO concentrations did not elevate at high altitudes. The EPAS1 and EGLN1 mRNA expressions were significantly lower in Sherpa highlanders compared to non-Sherpa lowlanders. Moreover, genotype distributions and allele frequencies of rs13419896 and rs4953354 in EPAS1, as well as rs1435166 and rs2153364 in EGLN1, differed significantly between Sherpa highlanders and non-Sherpa lowlanders. Analyses of the relative mRNA expressions of EPAS1 and EGLN1 by the SNPs suggested that the rs13419896/G and rs4953354/A alleles in EPAS1, as well as the rs1435166/G and rs2153364/A alleles in EGLN1, have down-regulatory effects on the gene mRNA expressions in Sherpa highlanders, contributing to inhibiting the EPO hypoxia response and exhibiting hypoxia-tolerant EPO levels in Sherpa highlanders. Natural selection, driven by high-altitude hypoxia, has encouraged adaptive evolution in Sherpa highlanders, including modifications in EPAS1 and EGLN1 genes. This evolutionary process leads to the downregulation of gene mRNA expressions, effectively tempering EPO responses to hypoxia and thereby enabling adaptation to high-altitude environments.

genetics↗

bioRxiv2024

Multifaceted roles of cohesin in regulating transcriptional loops

Cohesin is required for chromatin loop formation. However, its precise role in regulating gene transcription remains largely unknown. We investigated the relationship between cohesin and RNA Polymerase II (RNAPII) using single-molecule mapping and live-cell imaging methods in human cells. Cohesin-mediated transcriptional loops were highly correlated with those of RNAPII and followed the direction of gene transcription. Depleting RAD21, a subunit of cohesin, resulted in the loss of long-range (>100 kb) loops between distal (super-)enhancers and promoters of cell-type-specific genes. By contrast, the short-range (<50 kb) loops were insensitive to RAD21 depletion and connected genes that are mostly housekeeping. This result explains why only a small fraction of genes are affected by the loss of long-range chromatin interactions due to cohesin depletion. Remarkably, RAD21 depletion appeared to up-regulate genes located in early initiation zones (EIZ) of DNA replication, and the EIZ signals were amplified drastically without RAD21. Our results revealed new mechanistic insights of cohesins multifaceted roles in establishing transcriptional loops, preserving long-range chromatin interactions for cell-specific genes, and maintaining timely order of DNA replication.

genomics↗

bioRxiv2024

Loss of ZNRF3/RNF43 Unleashes EGFR in Cancer

ZNRF3 and RNF43 are closely related transmembrane E3 ubiquitin ligases with significant roles in development and cancer. Conventionally, their biological functions have been associated with regulating WNT signaling receptor ubiquitination and degradation. However, our proteogenomic studies have revealed EGFR as the protein most negatively correlated with ZNRF3/RNF43 mRNA levels in multiple human cancers. Through biochemical investigations, we demonstrate that ZNRF3/RNF43 interact with EGFR via their extracellular domains, leading to EGFR ubiquitination and subsequent degradation facilitated by the E3 ligase RING domain. Overexpression of ZNRF3 reduces EGFR levels and suppresses cancer cell growth in vitro and in vivo, whereas knockout of ZNRF3/RNF43 stimulates cell growth and tumorigenesis through upregulated EGFR signaling. Together, these data highlight ZNRF3 and RNF43 as novel E3 ubiquitin ligases of EGFR and establish the inactivation of ZNRF3/RNF43 as a driver of increased EGFR signaling, ultimately promoting cancer progression. This discovery establishes a connection between two fundamental signaling pathways, EGFR and WNT, at the level of cytoplasmic membrane receptors, uncovering a novel mechanism underlying the frequent co-activation of EGFR and WNT signaling in development and cancer.

cancer biology↗

bioRxiv2023

Breakage fusion bridge cycles drive high oncogene copy number, but not intratumoral genetic heterogeneity or rapid cancer genome change

Oncogene amplification is a major driver of cancer pathogenesis. Breakage fusion bridge (BFB) cycles, like extrachromosomal DNA (ecDNA), can lead to high copy numbers of oncogenes, but their impact on intratumoral heterogeneity, treatment response, and patient survival are not well understood due to difficulty in detecting them by DNA sequencing. We describe a novel algorithm that detects and reconstructs BFB amplifications using optical genome maps (OGMs), called OM2BFB. OM2BFB showed high precision (>93%) and recall (92%) in detecting BFB amplifications in cancer cell lines, PDX models and primary tumors. OM-based comparisons demonstrated that short-read BFB detection using our AmpliconSuite (AS) toolkit also achieved high precision, albeit with reduced sensitivity. We detected 371 BFB events using whole genome sequences from 2,557 primary tumors and cancer lines. BFB amplifications were preferentially found in cervical, head and neck, lung, and esophageal cancers, but rarely in brain cancers. BFB amplified genes show lower variance of gene expression, with fewer options for regulatory rewiring relative to ecDNA amplified genes. BFB positive (BFB (+)) tumors showed reduced heterogeneity of amplicon structures, and delayed onset of resistance, relative to ecDNA(+) tumors. EcDNA and BFB amplifications represent contrasting mechanisms to increase the copy numbers of oncogene with markedly different characteristics that suggest different routes for intervention.

cancer biology↗

bioRxiv2023

EagleC Explorer: A desktop application for interactively detecting and visualizing SVs and enhancer hijacking on Hi-C contact maps

It has been shown that Hi-C can be used as a powerful tool to detect structural variations (SVs) and enhancer hijacking events. However, there has been no existing programs that can directly visualize and detect such events on a personal computer, which hinders the broad adaption of the technology for intuitive discovery in cancer studies. Here, we introduce the EagleC Explorer, a desktop software that is specifically designed for exploring Hi-C and other chromatin contact data in cancer genomes. EagleC Explorer has a set of unique features, including 1) conveniently visualizing global and local Hi-C data; 2) interactively detecting SVs on a Hi-C map for any user-selected region on screen within seconds, using a deep-learning model; 3) reconstructing local Hi-C map surrounding user-provided SVs and generating publication-quality figures; 4) detecting enhancer hijacking events for any user-suggested regions on screen. In addition, EagleC Explorer can also incorporate other genomic tracks such as RNA-Seq or ChIP-Seq to facilitate scientists for integrative data analysis and making novel discoveries.

bioinformatics↗

bioRxiv2023

FAM210A mediates an inter-organelle crosstalk essential for protein synthesis and muscle growth in mouse

Mitochondria are not only essential for energy production in eukaryocytes but also a key regulator of intracellular signaling. Here, we report an unappreciated role of mitochondria in regulating cytosolic protein translation in skeletal muscle cells (myofibers). We show that the expression of mitochondrial protein FAM210A (Family With Sequence Similarity 210 Member A) is positively associated with muscle mass in mice and humans. Muscle-specific Myl1Cre-driven Fam210a knockout (Fam210aMKO) in mice reduces mitochondrial density and function, leading to progressive muscle atrophy and premature death. Metabolomic and biochemical analyses reveal that Fam210aMKO reverses the oxidative TCA cycle towards the reductive direction, resulting in acetyl-CoA accumulation and hyperacetylation of cytosolic proteins. Specifically, hyperacetylation of several ribosomal proteins leads to disassembly of ribosomes and translational defects. Transplantation of Fam210aMKO mitochondria into wildtype myoblasts is sufficient to elevate protein acetylation in recipient cells. These findings reveal a novel crosstalk between the mitochondrion and ribosome mediated by FAM210A.

cell biology↗

bioRxiv2023

Single Nuclei RNA Sequencing of the Gastrocnemius Muscle in Peripheral Artery Disease

BackgroundLower extremity peripheral artery disease (PAD) is a growing epidemic with limited effecOve treatment options. Herein, we provide a single nuclei atlas of PAD limb muscle to facilitate a better understanding of the composition of cells and transcriptional differences that comprise the diseased limb muscle. MethodsWe obtained gastrocnemius muscle specimens from 20 PAD patients and 12 non-PAD controls. Nuclei were isolated and single nuclei RNA sequencing (snRNAseq) was performed. The composition of nuclei was characterized by iteraOve clustering via principal component analysis, differenOal expression analysis, and the use of known marker genes. BioinformaOcs analysis was performed to determine differences in gene expression between PAD and non-PAD nuclei, as well as subsequent analysis of intercellular signaling networks. Additional histological analyses of muscle specimens accompany the snRNAseq atlas. ResultssnRNAseq analysis indicated a fiber type shim with PAD paOents having fewer Type I (slow/oxidaOve) and more Type II (fast/glycolyOc) myonuclei compared to non-PAD, which was confirmed using immunostaining of muscle specimens. Myonuclei from PAD displayed global upregulation of genes involved in stress response, autophagy, hypoxia, and atrophy. Subclustering of myonuclei also idenOfied populations that were unique to PAD muscle characterized by metabolic dysregulation. PAD muscles also displayed unique transcriptional profiles and increased diversity of transcriptomes in muscle stem cells, regeneraOng myonuclei, and fibro-adipogenic progenitor (FAPs) cells. Analysis of intercellular communication networks revealed FAPs as a major signaling hub in PAD muscle, as well as deficiencies in angiogenic and bone morphogeneOc protein signaling which may contribute to poor limb function in PAD. ConclusionsThis reference snRNAseq atlas provides a comprehensive analysis of the cell composition, transcriptional signature, and intercellular communication pathways that are altered in the PAD condition.

genomics↗

bioRxiv2023

Accurate identification of structural variations from cancer samples

Structural variations (SVs) are commonly found in cancer genomes. They can cause gene amplification, deletion, and fusion, among other functional consequences. With an average read length of hundreds of kilobases, nano-channel-based optical DNA mapping is powerful in detecting large SVs. However, existing SV calling methods are not tailored for cancer samples, which have special properties such as mixed cell types and sub-clones. Here we propose the COMSV method that is specifically designed for cancer samples. It shows high sensitivity and specificity in benchmark comparisons. Applying to cancer cell lines and patient samples, COMSV identifies hundreds of novel SVs per sample.

genomics↗