Biology subjects

Ma, G.

Publications and source records attributed to Ma, G..

At least 19 recordsLinked to original sources

bioRxiv2026

Human brain white matter charts in international populations

Brain charts provide normative references for identifying neurodevelopmental milestones and clinically meaningful deviations. Existing white matter (WM) charts are derived predominantly from European and North American populations, limiting generalizability. Here, we established the first set of population-specific WM charts of 198 morphological and microstructural phenotypes for both Chinese (N=19,215) and Western (N=15,584) populations across the human lifespan. Developmental trajectories and spatial organization of WM maturation and degeneration were broadly conserved across the populations, whereas maturational timing varied across pathways and metrics. The Chinese population showed earlier maturation in several projection and sensorimotor pathways, but more protracted maturation in higher-order association and limbic pathways. Chinese population-matched charts more accurately predicted WM phenotypes and detected more extreme disease-related deviations in brain health in the Chinese population than Western-derived models. Individual deviation patterns further discriminated patients from healthy controls and predicted cognitive performance and plasma biomarkers. Our findings reveal population-specific WM maturation and show that reference-population mismatch can reduce the accuracy and clinical sensitivity of normative brain charts.

neuroscience↗

bioRxiv2026

Ribonucleotide Reductase Inhibition Overcomes FLT3 Inhibitor Resistance in Acute Myeloid Leukemia

Internal tandem duplication mutations in FLT3 (FLT3ITD) occur in approximately 30% of patients with acute myeloid leukemia (AML) and are among the most common genetic alterations in this disease. FLT3ITD is a major driver of AML and is associated with poor clinical outcomes. Although FLT3 inhibitors (FLT3is) have significantly improved outcomes for patients with FLT3ITD+ AML, acquired resistance remains a major barrier to durable clinical benefit. Reactivation of RAS/MAPK signaling, often driven by activating NRAS mutations, is a major mechanism of FLT3i resistance in AML; however, effective strategies to overcome this resistance remain lacking. Here, we identify ribonucleotide reductase (RNR) as a critical therapeutic vulnerability in NRAS-driven FLT3i-resistant FLT3ITD+ AML. Activation of RAS signaling through SPRY3 loss or oncogenic NRAS mutations confers robust resistance to FLT3is, whereas pharmacologic inhibition of RNR with multiple inhibitors, as well as siRNA-mediated RNR suppression, reverses FLT3i resistance and restores FLT3i sensitivity across multiple FLT3ITD+ AML models in vitro. In vivo, clofarabine, an FDA-approved RNR inhibitor (RNRi), significantly overcomes NRAS mutation-driven FLT3i resistance. In combination with FLT3 inhibition, clofarabine markedly suppresses the progression of FLT3i-resistant AML and significantly prolongs survival in cell line-derived xenograft (CDX) models. Importantly, the therapeutic efficacy of the gilteritinib/clofarabine combination was independently validated in two genetically distinct patient-derived xenograft (PDX) models harboring different NRAS mutations, demonstrating robust reduction of leukemia burden and confirming the generalizability of RNR inhibition in primary FLT3i-resistant AML. Together, these findings identify a previously unrecognized therapeutic vulnerability in FLT3i-resistant FLT3mut+ AML and establish RNR inhibition as an effective strategy to overcome FLT3i resistance, providing a strong rationale for the clinical evaluation of RNRis in combination with FLT3is in patients with resistant AML. SignificanceAlthough FLT3 inhibitors (FLT3i) are an important therapeutic advance in FLT3ITD+ AML, resistance commonly develops. We identified ribonucleotide reductase (RNR) as a new key vulnerability in NRAS-driven FLT3i-resistant AML and demonstrated that multiple RNRis, including the FDA-approved agent clofarabine, restore FLT3i sensitivity and enhance antileukemic activity, supporting a clinically actionable combination strategy.

cancer biology↗

bioRxiv2026

Muscle March5 restrains an ATF4-GDF15 endocrine stress axis that modulates feeding and body composition

Skeletal muscle can release endocrine stress signals during aging and wasting, but the upstream mechanisms that restrain this response remain incompletely defined. Here we identify March5 as a muscle proteostatic checkpoint that limits ATF4-dependent GDF15 production. March5 expression declined in aged and atrophic muscle, whereas muscle-specific March5 deletion induced ATF4 accumulation, marked GDF15 elevation, reduced food intake and progressive loss of body, muscle and bone mass. Restoration of feeding, GDF15 neutralization or muscle Atf4 deletion substantially attenuated the wasting phenotype. Mechanistically, March5 interacted with ATF4 and promoted its ubiquitination at K92, thereby limiting ATF4 stability and Gdf15 expression. Conversely, muscle March5 gain-of-function or pharmacological attenuation of ATF4 signaling improved feeding, body composition and physical performance in aged mice. These findings define a March5-ATF4-GDF15 endocrine stress axis linking muscle proteostatic control to feeding suppression and systemic body-composition remodeling.

physiology↗

bioRxiv2026

SALL2 constrains TEAD4 by maintaining repressive chromatin to restrict trophectoderm identity

Embryonic development is marked by the successive restriction of developmental potential and the specification of embryonic and extraembryonic lineages. Yet, how these lineage decisions are established, and how the epigenome is remodelled to promote and restrict cell fate transitions, remains poorly understood. Here, we demonstrate that SALL2 knockdown in primed human pluripotent stem cells (hPSCs) triggers a trophectoderm (TE)-like phenotype, characterized by palisade-like morphology and the up-regulation of TE-associated genes. Mechanistically, SALL2 physically interacts with the key TE driver TEAD4 and maintains bivalent, repressive chromatin (H3K4me3/H3K27me3) at TE-specific loci. Reduced SALL2 led to enhanced TEAD4 occupancy and disrupted H3K27me3 and increased active chromatin marks at TE genes. Importantly, depletion of TEAD4 abolished the TE-like phenotype induced by SALL2 knockdown, demonstrating that TEAD4 is required for the downstream effects of SALL2 loss. In support of this, blastoid-like aggregates can be generated from primed hPSCs with SALL2 knocked down. Together, our findings identify SALL2 as a key epigenetic barrier that restrains TE lineage commitment by limiting TEAD4-dependent activation of the trophoblast transcriptional program. Key findingsO_LISALL2 acts as a molecular barrier to trophectoderm differentiation. C_LIO_LISALL2 suppresses the trophectoderm by maintaining bivalent repressive chromatin at TEAD4-bound loci. C_LIO_LIBlastoid-like structures can be generated from primed-state media when SALL2 was knocked down. C_LI O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=91 SRC="FIGDIR/small/737659v1_ufig1.gif" ALT="Figure 1"> View larger version (20K): org.highwire.dtl.DTLVardef@42cafaorg.highwire.dtl.DTLVardef@11c040borg.highwire.dtl.DTLVardef@4d9ffborg.highwire.dtl.DTLVardef@42546a_HPS_FORMAT_FIGEXP M_FIG C_FIG

cell biology↗

bioRxiv2026

Post-daunorubicin treatment effects on cardiovascular function in the Ts65Dn mouse model of Down syndrome

Adults with Down syndrome (DS) are two times more likely to be diagnosed with chronic heart failure post-anthracycline chemotherapy compared to age and sex-matched adults without DS. They have an elevated lifetime risk of cardiovascular diseases, increasing their likelihood of anthracycline-induced chronic cardiovascular toxicity. We investigated the chronic effects of daunorubicin on the cardiovascular system of the adult Ts65Dn mouse model of DS compared to wild type euploid mice (WT). WT and Ts65Dn mice received two doses of 2mg/kg or 4mg/kg of daunorubicin or saline and were monitored for up to 117 days. Cardiac and vascular function were evaluated using left ventricular catheterization, histology, pulse wave velocity, and cardiac troponin tests. Survival significantly decreased in the Ts65Dn 4mg/kg group compared to saline controls (p<0.001). Further experiments were carried out with the saline and 2mg/kg groups, which exhibited lower mortality, more consistent with chronic toxicity. Body weight (p=0.001), end-diastolic pressure (p=0.016), and left ventricular mass (p=0.021) decreased in treated mice. The effect of treatment differed significantly between strains for ejection fraction (p=0.029). Pulse wave velocity increased over time (p<0.001). A significant interaction between treatment and strain was observed for collagen in both the left ventricles and thoracic aorta (p=0.002 and p<0.001, respectively). There was a strain difference for cardiac troponin I, indicating an increase in Ts65Dn mice (p=0.020). Daunorubicin treatment results in a distinct cardiovascular remodeling phenotype in Ts65Dn mice. More mechanistic studies are warranted to outline the pathophysiology of anthracycline cardiovascular toxicity in DS.

cancer biology↗

bioRxiv2026

Exploration of Orally Disintegrating Tablet for Sublingual Vaccination against Mucosal Bacterial Infection

Oral mucosal bacterial infections impose a substantial global disease burden, yet current clinical management typically reduces microbial load only transiently and rarely establishes durable protection at the oral surface. Analysis of 200 patients with periodontitis revealed that elevated levels of pathogen-specific salivary secretory Immunoglobulin A (sIgA) were strongly associated with reduced bacterial burden and improved clinical periodontal outcomes, identifying sIgA as a key determinant of effective oral protection. Guided by this observation, we developed a sublingual, orally disintegrating tablet vaccine (Capot) that incorporates bacterial extracellular vesicles providing a comprehensive repertoire of native antigens and multiple pathogen-associated molecular patterns, encapsulated within a calcium phosphate nanoshell to enable safe transmucosal delivery to submandibular lymph nodes. The rapidly disintegrating tablet format minimizes inadvertent swallowing and enhances local mucosal bioavailability. In mice and non-human primates, Capot induced robust and long-lasting salivary sIgA responses without overt oral mucosal or gastrointestinal inflammation and conferred strong protection against primary, recurrent, and antibiotic-resistant periodontitis. Together, these findings establish sublingual tablet vaccination as a practical strategy for selectively engaging oral mucosal immunity and preventing chronic bacterial diseases at oral mucosal surfaces.

bioengineering↗

bioRxiv2026

A human gut-BBB-brain microphysiological model for studying neurodegenerative diseases

The gut-brain axis has emerged as a crucial factor in neurodegeneration, with growing evidence linking gut dysbiosis and metabolic dysfunction to Alzheimers disease (AD) progression. Unfortunately, the lack of human-relevant in vitro models limits our ability to effectively explore the mechanism of this axis. To address this gap, we have developed a human induced pluripotent stem cell (iPSC)-derived gut-blood-brain barrier (BBB)-brain microphysiological system that enables systematic investigation of gut-brain interaction in the context of AD under controlled conditions. Our findings reveal that the interaction between gut and brain organoids can promote the maturation of brain organoids, making them more similar to their physiological characteristics in vivo. Additionally, co-culture gut and brain organoids better recapitulates the pathological features of AD. We also discovered that gut organoids of AD can trigger neurodegenerative disease manifestations in healthy brain organoids. In summary, our microphysiological system provides a novel and versatile in vitro platform for studying the interaction between the gut and brain in neurodegenerative diseases.

neuroscience↗

bioRxiv2025

The m6A reader protein YTHDF2 facilitates HTLV-1 infectious and mitotic propagation by stabilizing Tax RNA

N6-methyladenosine (m6A) is one of the important RNA modifications that affect RNA abundance and function and has also been implicated in viral infection. In this study, we identify a number of m6A modification sites within human T-cell leukemia virus type 1 (HTLV-1) RNAs, particularly in the RNA of the Tax oncogene. We demonstrate that YTH domain family, member 2 (YTHDF2), a key m6A reader protein that binds m6A-modified RNAs and influences RNA metabolism, is required for HTLV-1 replication in both de novo and persistently infected cells. Mechanistically, YTHDF2 interacts with and stabilizes Tax RNA in an m6A-dependent manner, thereby promoting Tax-driven HTLV-1 replication. Importantly, YTHDF2 activates oncogenic cellular pathways and promotes proliferation in HTLV-1 infected cells, aligning with the functions of Tax. Overall, our findings characterize YTHDF2 as a host factor critical to HTLV-1 RNA metabolism and viral propagation, offering novel insights into the understanding of HTLV-1 life cycle and the development of targeted interventions. Importancem6A is an RNA modification that plays crucial roles in physiological and pathological conditions; however, its roles in HTLV-1 infection are poorly understood. In this study, we identify that m6A modification is widely present in HTLV-1 RNAs including Tax. We demonstrate that YTHDF2, a prominent m6A reader protein, enhances the stability of Tax RNA, thereby promoting both de novo and persistent HTLV-1 replication. Our findings position YTHDF2 as an essential factor for HTLV-1 persistence and suggest it as a potential therapeutic target for viral clearance.

microbiology↗

bioRxiv2025

Plant Face: Machine learning decodes genetic, environmental and developmental imprints in leaf appearance

Leaf appearance is a crucial plant phenotype. However, traditional methods for extracting this information are inefficient, limiting its full utilization. Deep learning based on convolutional neural networks (CNNs) enables us to capture previously inaccessible information from images. In this study, we made the surprising discovery that the leaf appearance of each individual plant is unique. Using deep learning, leaves from one plant could be efficiently distinguished from those of another plant of the same species and cultivar. We term this phenomenon the "Plant Face" and suggest the potential to develop a "plant face recognition system," analogous to human facial recognition. We also applied similar methods to study the relationship between leaflet appearance and their position on compound leaves, leaf bilateral symmetry, and differences in leaves from twining stems with different chirality. These results collectively indicate that plant genetic characteristics, growth conditions, and developmental features can be stored within their appearance. With appropriate decoding, leaf appearance is poised to play an increasingly important role in phenomics. SignificanceThe saying "no two leaves in the world are identical" holds philosophical significance, as such variation encompasses considerable contingency and randomness. Here, we assert that no two trees have identical leaves; meaning that even for plants of the same species and cultivar, the leaf morphology of each individual plant is distinct at the population level, even though single leaves may overlap in appearance. Genetic, environmental, and developmental information is recorded in some manner within the phenotypic appearance of leaves. With advancements in computational technologies like artificial intelligence, this information can now be decoded. HighlightsO_LIThe leaves of each individual plant are statistically unique. C_LIO_LIThe relationship between leaflet appearances in compound leaves hints at their developmental patterns. C_LIO_LILeaves are not necessarily bilaterally symmetric in a statistical sense. C_LIO_LILeaves from stems with different chirality (twining direction) exhibit distinct appearances. C_LI

plant biology↗

bioRxiv2025

CARP Protects Against Doxorubicin-induced Cardiotoxicity through NRF1-driven Mitochondrial Homeostasis

AimsDoxorubicin (DOX), a highly effective anthracycline chemotherapeutic agent, is limited by its dose-dependent cardiotoxicity. This study investigates the cardioprotective mechanisms of cardiac adriamycin responsive protein (CARP) and its underlying mechanisms in DOX-induced cardiotoxicity (DIC). Methods and resultsCardiac-specific CARP transgenic and wild-type mice were subjected to a DIC model. Cardiac function was assessed via echocardiography, histopathology, and transmission electron microscopy (TEM). In vitro, DOX-treated cardiomyocytes overexpressing CARP were analyzed for oxidative stress (ROS levels), mitochondrial function (mtDNA copy number etc.), and mitochondrial-related proteins (Western blot). CARP-NRF1 interaction was validated by co-immunoprecipitation (Co-IP), and NRF1 siRNA knockdown was performed to assess CARPs role in mitochondrial homeostasis. CARP overexpression markedly alleviated DOX-induced cardiac dysfunction and mitochondrial damage, restoring mitochondrial dynamics and mitophagy. Mechanistically, CARP directly interacted with NRF1, and NRF1 knockdown ameliorated CARP-mediated cardioprotection in DIC. ConclusionCARP safeguards against DIC by maintaining mitochondrial homeostasis via NRF1 signaling, positioning it as a promising therapeutic target for DOX-induced cardiomyopathy.

molecular biology↗

bioRxiv2025

A single-component optogenetic toolkit for programmable control of microtubule

Microtubules (MTs) form dynamic cytoskeletal scaffolds essential for intracellular transport, organelle positioning, and spatial organization of signaling. Their architecture and function are continuously remodeled through the concerted actions of microtubule-associated proteins (MAPs), post-translational modifications (PTMs), and molecular motors. To precisely interrogate these processes in living systems, we developed a genetically encoded optogenetic toolkit for spatiotemporal control of MT organization and dynamics. By replacing native multimerization motifs with a blue light-responsive oligoermization domain, we have engineered single-component probes, OptoMT and OptoTIP, that reversibly label MT polymers or track plus-ends with tunable kinetics from seconds to minutes. When coupled to enzymatic effectors, these modules enable localized tubulin acetylation or detyrosination, directly linking PTMs to MT stability. We further engineered OptoMotor, a light-activatable kinesin platform that reconstitutes tail-dependent cargo transport along MTs, and OptoSAW, a light-triggered severing actuator for controlled MT disassembly. Using these tools, we reveal how local MT integrity governs lysosomal trafficking and ER-associated signaling dynamics. Collectively, this versatile single-component toolkit bridges molecular design with cytoskeletal function, offering new avenues to illuminate how dynamic cytoskeletal architectures coordinate intracellular organization, transport, and signaling.

cell biology↗

bioRxiv2025

Thioredoxin-1 inhibits granulosa cell ferroptosis to rescue ovarian aging through mitophagy-dependent activation of BNIP3L

Ovarian aging is closely associated with a decline in fertility and an increase in reproductive dysfunction. Ovarian granulosa cells (GCs) support oocyte homeostasis and development, yet insight into GC dysfunction during aging is limited. Here, we show that aged GCs of humans and mice have indications of elevated ferroptosis, including increased ferroptosis-related metabolites, lipid peroxidation, and iron accumulation. The ferroptosis inhibitor Ferrostatin-1 reversed ovarian impairment and fertility of aged mice in vivo. We show that the age-related reduction in the expression of TXN (thioredoxin) leads to ferroptosis in human and mouse GCs by blocking BNIP3L-dependent mitophagy. Exogenous activation of TXN could promote mitophagy, thereby clearing excessive ROS and inhibiting ferroptosis. These results suggest that anti-ferroptosis-related treatments may assist in treating aging-related reproductive disorders. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=107 SRC="FIGDIR/small/664497v1_ufig1.gif" ALT="Figure 1"> View larger version (26K): org.highwire.dtl.DTLVardef@1b97e8forg.highwire.dtl.DTLVardef@123f8d0org.highwire.dtl.DTLVardef@a44c61org.highwire.dtl.DTLVardef@92b32e_HPS_FORMAT_FIGEXP M_FIG C_FIG Key pointsO_LIFerroptosis signatures are upregulated in aged GCs from human and mouse ovaries C_LIO_LITXN is deregulated in aged GCs, leading to mitochondrial and ROS metabolic dysfunction C_LIO_LITXN binds to DNA to regulate autophagy and mitophagy genes, including BNIP3L C_LIO_LIInhibition of ferroptosis can ameliorate GC dysfunction C_LI

cell biology↗

bioRxiv2024

Astrocyte-specific secretome profiling reveals its correlation with neurological disorders

Secreted proteins mediate intercellular communication throughout the lives of multicellular organisms. However, due to the lack of new technology for secreted protein capturing, the progress of "secretomics lags behind. Here, we report a two-step secretome enrichment method (tsSEM) combining unnatural amino acid labeling and click chemistry-based biorthogonal reaction, which enables in vitro secretome profiling in the presence of serum. Using this novel method, we systematically investigated the secretome of human iPSCs-derived astrocytes (iAst) in different disease models and identified a panel of astrocyte-secreted proteins that are responsible for its non-cell autonomous toxicity under disease conditions. Furthermore, we validated two astrocytes-derived novel neurotrophic proteins, FAM3C and KITLG, which we identified from disease models, and found that they could boost neurite outgrowth, protect neurons, and promote neural progenitor proliferation. Our study highlights the utility of secretome profiling of iAst and demonstrates its applications in disease study and target identification and validation in drug development.

neuroscience↗

bioRxiv2024

Dissecting the Contribution of Transposable Elements to Interphase Chromosome Structure

Transposable elements (TEs) occupy nearly half of the human genome and play diverse biological roles. Despite their abundance, the extent to which TEs contribute to three-dimensional (3D) genome structure remains unclear. To investigate this, we developed te_hic, a computational pipeline that integrates genomic data with chromatin interactions. Our analysis reveals that TE sequences are responsible for 3D genome structure in interphase nuclei. This phenomenon is mediated by the recruitment of specific transcription factors to TEs, which enables both the formation and disruption of chromatin contacts. We computationally identified known contact-forming proteins (CTCF, RAD21, SMC3) and breaking proteins (RNF2), as well as novel candidate contact-formers (SMARCA4, MAFK). Knockdown of the predicted contact-formers SMARCA4 and MAFK decreased contacts and loops at and between TEs. Notably, SMARCA4 knockdown selectively reduced short-range contacts, highlighting its role in maintaining 3D genome structure mediated by TE binding. Overall, our findings demonstrate that TEs are crucial determinants of 3D genome organization in mammalian cells. Key findingsO_LITEs determine 48% of the 3D genome structure alone, and 70% of heterotypic contacts. C_LIO_LIA/B compartments, TADs, and loop signatures can be retrieved using TE-mapped reads only. C_LIO_LITFs can be divided into contact formers and breakers at TEs. C_LIO_LISMARCA4 and MAFK build chromatin contacts between TE sequences. C_LI

cell biology↗

bioRxiv2024

Integrated temporal profiling of iPSCs-derived motor neurons from ALS patients carrying C9orf72, FUS, TARDBP, and SOD1 mutations

Amyotrophic Lateral Sclerosis (ALS) is a lethal neurodegenerative disease that damages motor neurons in the central nervous system, causing progressive muscle weakness that ultimately leads to death. However, its underlying mechanisms still need to be fully understood, particularly the heterogeneity and similarity between various gene mutants during disease progression. In this study, we conducted temporal RNA-seq profiling in human induced pluripotent stem cells (hiPSCs) and iPSC-derived motor neurons (iMNs) carrying the C9orf72, FUS, TARDBP, and SOD1 mutations from both ALS patients and healthy individuals. We discovered dysregulated gene expression and alternative splicing (AS) throughout iMN development and maturation, and ALS iMNs display enrichment of cytoskeletal defects and synaptic alterations from premature stage to mature iMNs. Our findings indicate that synaptic gene dysfunction is the common molecular hallmark of fALS, which might result in neuronal susceptibility and progressive motor neuron degeneration. Analysis of upstream splicing factors revealed that differentially expressed RNA-binding proteins (RBPs) in ALS iMNs may cause abnormal AS events, suggesting the importance of studying RBP defects in ALS research. Overall, our research provides a comprehensive and valuable resource for gaining insights into the shared mechanisms of ALS pathogenesis during motor neuron development and maturation in iMN models.

neuroscience↗

bioRxiv2024

Cost-effective DNA storage with DNA movable type

In the face of exponential data growth, DNA-based storage offers a promising solution for preserving big-data. However, most existing DNA storage methods, akin to traditional block printing, require costly chemical synthesis for each individual data file, adopting a sequential, one-time-use synthesis approach. To overcome these limitations, we introduce a novel, cost-effective "DNA-Movable-Type Storage" system, inspired by movable type printing. This system utilizes pre-fabricated DNA movable types-short, double-stranded DNA oligonucleotides encoding specific payload, address, and checksum data. These DNA-MTs are enzymatically ligated/assembled into cohesive sequences, termed "DNA movable type blocks", streamlining the assembly process with the automated BISHENG-1 DNA-MT inkjet printer. Using BISHENG-1, we successfully printed, assembled, stored and accurately retrieved 43.7 KB of data files in diverse formats (text, image, audio, and video) in vitro and in vivo, using only 350 DNA-MTs. Notably, each DNA-MT, synthesized once (2 OD), can be used up to 10,000 times, reducing costs to 122 $/MB-outperforming existing DNA storage methods. This innovation circumvents the need to synthesize entire DNA sequences encoding files from scratch, offering significant cost and efficiency advantages. Furthermore, it has considerable untapped potential to advance a robust DNA storage system, better meeting the extensive data storage demands of the big-data era.

bioinformatics↗

bioRxiv2024

Transposable Element Expression and Sub-cellular Dynamics During hPSC Differentiation to Endoderm, Mesoderm, and Ectoderm Lineages

Transposable elements (TEs) are genomic elements that are found in multiple copies in mammalian genomes. TEs were previously thought to have little functional relevance but recent studies have reported TE roles in multiple biological processes, particularly in embryonic development. To investigate the expression dynamics of TEs during human early development, we used long-read sequence data generated from in vitro differentiation of human pluripotent stem cells (hPSCs) to endoderm, mesoderm, and ectoderm lineages to construct lineage-specific transcriptome assemblies and accurately place TE sequences in their transcript context. Our analysis revealed that specific TE types, such as LINEs and LTRs, exhibit distinct expression patterns across different lineages. Notably, an expression outburst was observed in the ectoderm lineage, with multiple TE types showing dynamic expression trajectories. Additionally, certain LTRs, including HERVH and LTR7Y, were highly expressed in hPSCs and endodermal cells, but these HERVH and LTR7Y sequences originated from completely different transcripts. Interestingly, TE-containing transcripts exhibit distinct levels of transcript stability and subcellular localization across different lineages. Moreover, we showed a consistent trend of increased chromatin association of TE-containing transcripts in germ lineage cells compared to hPSCs. This study suggests that TEs contribute to human embryonic development through dynamic chromatin interactions. Key findingsO_LIDifferent loci of the same TEs are independently regulated in different cell states C_LIO_LIEctoderm has the highest frequency of TE-containing transcripts C_LIO_LIThe presence of TEs dynamically drives transcripts to different sub-cellular compartments in different cell states C_LIO_LIhPSCs have the least stable TE transcripts with the weakest TE chromatin association, highlighting loose hPSC chromatin and potential roles in cell differentiation C_LI

genomics↗

bioRxiv2024

Label-Free Electrochemical Imaging of Single Extracellular Vesicles

Extracellular vesicles (EVs) are pivotal in various biological processes and diseases, yet their small size and heterogeneity pose challenges for single EV quantification. We introduce interferometric electrochemical microscopy (iECM), a sensitive label-free technique that combines interferometric scattering and electrochemical impedance imaging. This method enables the quantification of the impedance of single EVs, providing unique insights into their electrochemical properties, and allows for the simultaneous measurement of size and real-time monitoring of antibody binding. Notably, we discovered that the impedance spectra of EVs can serve as unique fingerprints to differentiate EVs from cancerous and healthy cells, offering potential advancements in clinical diagnostics and the profiling of extracellular biomarkers.

biophysics↗