Biology subjects

Cai, Y.

Publications and source records attributed to Cai, Y..

At least 109 records · Page 6Linked to original sources

bioRxiv2024

Genomics-FM: Universal Foundation Model for Versatile andData-Efficient Functional Genomic Analysis

Artificial intelligence (AI) plays a crucial role in functional genomic analysis, offering great potential for comprehending biological phenomena such as heredity, development, diseases, and evolution. However, the development of AI models needs substantial labeled data, and these models are typically task-specific with limited generalizability to various applications. Here, we develop Genomics-FM, a genomic vocabulary driven foundation model that enables versatile and label-efficient functional genomic analysis. Specifically, Genomics-FM is first pretrained with ensemble genomic vocabulary on vast unlabelled data to learn comprehensive and generalizable representations and then finetuned with specific genomic vocabulary on limited labeled data to selectively activate and adapt the pretraining knowledge for specific tasks. We show that Genomics-FM significantly reduces the dependence on labeled data, and demonstrates the capability to outperform existing models across a comprehensive suite of tasks including genome annotation, epigenomic and expression profile prediction, and variant effect assessment. Remarkably, Genomics-FM even shows impressive zero-shot predictive capabilities across diverse species and tissues and exhibits noticeable adaptability to RNA-related tasks. With feasibility in data scarcity and even cross-domain biological scenarios, Genomics-FM will promote the broad application of AI and empower researchers to tackle previously insurmountable challenges, paving the way for groundbreaking research and discoveries.

bioinformatics↗

bioRxiv2024

Dynamin 1-mediated endocytic recycling of glycosylated N-cadherin sustains the plastic mesenchymal state to promote ovarian cancer metastasis

Epithelial-to-mesenchymal transition (EMT) is a key process that confers metastatic plasticity to ovarian cancer cells, enabling them to disseminate aggressively throughout the peritoneal cavity and contributing to poor clinical outcomes for patients. However, a pharmacologically exploitable driver of EMT in ovarian cancer has yet to be identified. To address this, we utilized a master regulators algorithm to prioritize EMT regulators from a dataset of over 8,000 patient samples, including multidimensional omics data from more than 20 cancer types in TCGA. Further analysis identified dynamin-1 (DNM1), an endocytic regulator, as a novel master regulator of EMT in ovarian cancer. Clinically, DNM1 overexpression was found to be associated with the mesenchymal subtype and advanced/metastatic stages of ovarian carcinomas. Molecular assays revealed that DNM1 upregulates N-cadherin, a hallmark mesenchymal marker, by promoting its endocytosis and recycling, thereby inducing cell polarization and motility. In addition, integration of ATAC-seq and RNA-seq analyses uncovered the repression of beta-1,3-galactosyltransferase (B3GALT1), a glycosyltransferase, in metastatic cells. B3GALT1-mediated glycosylation hindered the recycling of N-cadherin. Functional studies demonstrated that depletion of DNM1 or pharmacological inhibition of endocytic recycling significantly impaired cell polarity, migration, and also cancer stemness. Importantly, in vivo experiments showed that the loss of DNM1 significantly suppressed peritoneal metastatic colonization. Interestingly, metastatic cells with elevated DNM1-mediated endocytosis showed increased susceptibility to nanoparticle delivery. Collectively, these results establish the DNM1-N-cadherin axis as an important regulator of EMT-associated ovarian cancer metastasis and suggest its potential as a biomarker for targeted nanodrug therapy.

cancer biology↗

bioRxiv2024

The noncoding circular RNA circHomer1 regulates developmental experience-dependent plasticity in mouse visual cortex

Circular RNAs (circRNAs) are a class of closed-loop, single stranded RNAs whose expression is particularly enriched in the brain. Despite this enrichment and evidence that the expression of circRNAs are altered by synaptic development and in response to synaptic plasticity in vitro, the regulation by and function of the majority of circRNAs in experience-dependent plasticity in vivo remain unexplored. Here, we employed transcriptome-wide analysis comparing differential expression of both mRNAs and circRNAs in juvenile mouse primary visual cortex (V1) following monocular deprivation (MD), a model of experience-dependent developmental plasticity. Among the differentially expressed mRNAs and circRNAs following 3-day MD, the circular and the activity-dependent mRNA forms of the Homer1 gene, circHomer1 and Homer1a respectively, were of interest as their expression changed in opposite directions: circHomer1 expression increased while the expression of Homer1a decreased following 3-day MD. Knockdown of circHomer1 delayed the depression of closed-eye responses normally observed after 3-day MD. circHomer1-knockdown also led to a reduction in average dendritic spine size prior to MD but critically there was no further reduction after 3-day MD, consistent with impaired structural plasticity. circHomer1-knockdown also prevented the reduction of surface AMPA receptors after 3-day MD. Synapse-localized puncta of the AMPA receptor endocytic protein Arc increased in volume after MD but were smaller in circHomer1-knockdown neurons, suggesting that circHomer1 knockdown impairs experience-dependent AMPA receptor endocytosis. Thus, the expression of multiple circRNAs are regulated by experience-dependent developmental plasticity, and our findings highlight the essential role of circHomer1 in V1 synaptic development and experience-dependent plasticity. Significance StatementCircular RNAs (circRNAs) are a class of closed-loop RNAs formed through back-splicing of exon and/or intron junctions. Initially considered as byproducts of aberrant RNA splicing with limited function, recent studies have implicated circRNAs in various neurological disorders. Despite their abundant expression in the brain, the role of circRNAs in experience-dependent plasticity remains poorly understood. We conducted an in vivo transcriptome analysis of circRNAs whose expression was regulated by experience-dependent plasticity in the mouse visual cortex and highlight circHomer1, a circRNA derived from the Homer1 gene, as a circRNA critical for synaptic development and experience-dependent plasticity in vivo.

neuroscience↗

bioRxiv2024

Microglia-specific transduction via AAV11 armed with IBA1 promoter and miRNA-9 targeting sequences

Microglia, as resident immune cells in the central nervous system (CNS), are closely related to human health and the pathogenesis of various CNS diseases, making them compelling targets for therapeutic interventions. However, functional and therapeutic studies of microglia remain significant challenges largely due to the lack of tools capable of efficiently and specifically transducing microglia. Herein, we evaluated the specificity and efficiency of various adeno-associated virus (AAV) vectors armed with the mIBA1 promoter and miRNA-9 targeting sequences in transducing microglia within the caudate putamen (CPu) brain region, and found that AAV11 mediates more specific and efficient transduction of microglia. Subsequently, we further demonstrated that AAV11 also exhibits high transduction specificity for microglia across various brain areas and within the spinal cord. Finally, by reducing the injection dosage, we employed AAV11 for sparse labeling of microglia. This work provides a promising tool for advancing both the functional investigation and therapeutic targeting of microglia.

neuroscience↗

bioRxiv2024

Temporal-spatially metabolic reprogramming rewires the H3K27ac landscape to enable the initiation of liver regeneration

The liver possesses extensive regenerative capacity. Nevertheless, the most proximal events driving the transition from quiescent to proliferative hepatocytes remain largely elusive. Using the combination of spatiotemporal metabolomics and transcriptomics, our study mapped out the temporal-spatial landscape of metabolic reprogramming, epigenetic remodeling, and transcriptomic rewiring from 3 to 12 hours post-partial hepatectomy. Specifically, we identified a profound metabolic shift towards hyperactive fatty acid oxidation (FAO) and suppressed phospholipid biosynthesis during the preparation phase of liver regeneration, which were surprisingly reversed afterwards. FAO-dependent accumulation of Acetyl-CoA particularly remodeled H3K27ac landscape. These metabolic reprograming and epigenetic regulation were spatially specific, aligning with the zonation of hepatocyte proliferation. Blocking FAO in etomoxir-treated or hepatocyte-specific Cpt1a knockout mice, suppressing Acetyl-CoA biosynthesis, and inhibiting histone acetyltransferase all resulted in lethal liver regeneration deficiency. CUT&Tag analysis further revealed that the reshaping of H3K27ac profiles favored the transcription of genes associated with cell cycle transition and mitosis, and rewired the metabolic gene network. Collectively, we highlight a previously underappreciated role of FAO in epigenetic remodeling that is essential for the initiation of liver regeneration, offering exciting opportunity for the rescue of regeneration-deficient livers. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=181 HEIGHT=200 SRC="FIGDIR/small/602368v1_ufig1.gif" ALT="Figure 1"> View larger version (61K): org.highwire.dtl.DTLVardef@8dd836org.highwire.dtl.DTLVardef@6ddb27org.highwire.dtl.DTLVardef@4f1e49org.highwire.dtl.DTLVardef@4d7afe_HPS_FORMAT_FIGEXP M_FIG C_FIG

cell biology↗

bioRxiv2024

Large-scale genome analyses provide insights into Hymenoptera evolution

The order Hymenoptera includes a large number of species with diverse lifestyles and is known for its significant contributions to natural ecosystems. To better understand the evolution of this diverse order, we performed large-scale comparative genomics on 131 species from 13 superfamilies, covering most representative groups. We used these genomes to reveal an overall pattern of genomic change in terms of gene content and evolutionary rate throughout hymenopteran history. We identified genes that possibly contributed to the evolution of several key innovations, such as parasitoidism, wasp-waist, sting, and secondary phytophagy. We also discovered the distinct genomic trajectories between the clade containing major parasitoid wasps (Parasitoida) and stinging species (Aculeata) since their divergence, which are involved in many aspects of genomic change, such as rapidly evolving gene families, gene gain and loss, and metabolic pathway evolution. In addition, we explored the genomic features accompanying the three independent evolution of secondary phytophagy. Our work provides insights for understanding genome evolution and the genomic basis of diversification in Hymenoptera.

genomics↗

bioRxiv2024

BEACON: Benchmark for Comprehensive RNA Tasks and Language Models

RNA plays a pivotal role in translating genetic instructions into functional outcomes, underscoring its importance in biological processes and disease mechanisms. Despite the emergence of numerous deep learning approaches for RNA, particularly universal RNA language models, there remains a significant lack of standardized benchmarks to assess the effectiveness of these methods. In this study, we introduce the first comprehensive RNA benchmark BEACON (BEnchmArk for COmprehensive RNA Task and Language Models). First, BEACON comprises 13 distinct tasks derived from extensive previous work covering structural analysis, functional studies, and engineering applications, enabling a comprehensive assessment of the performance of methods on various RNA understanding tasks. Second, we examine a range of models, including traditional approaches like CNNs, as well as advanced RNA foundation models based on language models, offering valuable insights into the task-specific performances of these models. Third, we investigate the vital RNA language model components from the tokenizer and positional encoding aspects. Notably, our findings emphasize the superiority of single nucleotide tokenization and the effectiveness of Attention with Linear Biases (ALiBi) over traditional positional encoding methods. Based on these insights, a simple yet strong baseline called BEACON-B is proposed, which can achieve outstanding performance with limited data and computational resources. The datasets and source code of our benchmark are available at https://github.com/terry-r123/RNABenchmark.

bioinformatics↗

bioRxiv2024

Inter-cellular mRNA Transfer Alters Human Pluripotent Stem Cell State

Inter-cellular transmission of mRNA is being explored in mammalian species using immortal cell lines (1-3). Here, we uncover an inter-cellular mRNA transfer phenomenon that allows for the adaptation and reprogramming of human primed pluripotent stem cells (hPSCs). This process is induced by the direct cell contact-mediated coculture with mouse embryonic stem cells (mESCs) under the condition impermissible for human primed PSC culture. Mouse-derived mRNA contents are transmitted into adapted hPSCs only in the coculture. Transfer-specific mRNA analysis show the enrichment for divergent biological pathways involving transcription/translational machinery and stress-coping mechanisms, wherein such transfer is diminished when direct cell contacts are lost. After 5 days of mESC culture, surface marker analysis, and global gene profiling confirmed that mRNA transfer-prone hPSC efficiently gains a naive-like state. Furthermore, transfer-specific knockdown experiments targeting mouse-specific transcription factor-coding mRNAs in hPSC show that mouse-derived Tfcp2l1, Tfap2c, and Klf4 are indispensable for human naive-like conversion. Thus, inter-species mRNA transfer triggers cellular reprogramming in mammalian cells. Our results support that episodic mRNA transfer can occur in cell cooperative and competitive processes(4), which provides a fresh perspective on understanding the roles of mRNA mobility for intra- and inter-species cellular communications.

cell biology↗

bioRxiv2024

Transcranial Direct Current Stimulation over the Posterior Parietal Cortex Increases Non-target Retrieval during Visual Working Memory

Accurate visual working memory (VWM) requires precise content-context binding. Previous studies have revealed a close relationship between the posterior parietal cortex (PPC) and feature binding during VWM, this study further examined their causal relationship through three transcranial direct current stimulation (tDCS) experiments. In Experiment 1 (N = 57), participants underwent three sessions of tDCS separately, including PPC stimulation, occipital cortex stimulation, and sham stimulation, and completed a series of delayed estimation tasks for orientations before and after stimulation. Results showed that tDCS over PPC selectively prolonged recall response time (RT) and increased the probability of non-target responses (a.k.a. failure of feature binding). In Experiment 2 (N = 29), combining metacognition estimation during the task, we further investigated whether the effects of PPC stimulation on RT and increased probability of non-target responses were attributed to more mis-binding (i.e., participants self-reported "remembered" in non-target responses) or informed guessing (participants self-reported "forgotten" in non-target responses). We replicated the main findings in Experiment 1, and we also observed greater tDCS effects of PPC on RT in informed guessing trials than mis-binding trials while comparable effects on non-target response rates in these two types of trials. In Experiment 3 (N = 28), we then examined whether the effects of tDCS over PPC specifically influenced the memory retrieval process by using a change detection task. We found that PPC stimulation did not influence the recognition RT or accuracy. Together, this study provides causal evidence supporting the involvement of PPC in feature binding during VWM retrieval. Significance StatementVisual working memory (VWM) enables humans to temporarily store and process visual information, which requires accurate binding of items to their unique context. Accumulating studies posited that the posterior parietal cortex (PPC) is closely related to this binding process, the current study further examined their causal relationship. Through three strictly within-subject well-designed non-invasive neural stimulation experiments, we found that PPC stimulation selectively increased response time (RT) and binding error during VWM. Moreover, we found these changes were modulated by individual metacognition and only occurred during memory recall instead of recognition. Together, our results provided strong evidence that PPC is causally involved in the binding process during visual working memory retrieval.

neuroscience↗

bioRxiv2024

Maternal Immunoglobulin A regulates the development of the neonatal microbiota and intestinal microbiota-specific CD4+ T cell responses

Breast milk is a complex mixture of nutrients and bioactives that promote infant development and decrease the incidence of chronic inflammatory disease. We investigated the role of one milk-derived bioactive, Immunoglobulin A (IgA) on the developing small intestinal microbiota and immune system. We demonstrate that early in life, milk-derived IgA suppressed colonization of the small intestine by Enterobacteriaceae and regulated the maturation of the small intestinal epithelium and the development of intestinal IL-17-producing CD4+ T cells. Enterobacteriaceae- specific CD4+ T cells, induced in the first weeks of life in the absence of milk-derived IgA, persisted in the intestine as memory T cells that can contribute to inflammatory disease later in life. Our study suggests that milk-derived IgA shapes mucosal immunity by regulating the neonatal microbiota thus preventing the development of long-lived intestinal microbiota-specific T cells.

immunology↗

bioRxiv2024

Microglia replacement effectively attenuates the disease progress of ALSP in the mouse model and human patient

Microglia play critical roles in the brain physiology and pathology. CSF1R is primarily expressed in microglia. The mono-allelic CSF1R mutation causes adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP), a lethal neurological disease and no rational cure in clinical trials. There are no animal models mimicking human ALSP. In this study, we first developed mouse models based on human ALSP hotspot mutations. We then utilized microglia replacement by bone marrow transplantation (Mr BMT) to replace the Csf1r-deficient microglia in ALSP mice by Csf1r-normal donor cells. With pathogenic gene correction, Mr BMT efficiently attenuated the pathologies. Previously, an ALSP patient received traditional bone marrow transplantation (tBMT) due to a misdiagnosis of metachromatic leukodystrophy. The disease progress was halted for 15 years with unknown reasons. We demonstrated that tBMT in ALSP is equivalent to or close to Mr BMT, achieving efficient microglia replacement and therefore attenuating the ALSP progress in the mouse model. Next, we applied tBMT to replace CSF1R-deficient microglia in human patients. Our clinical results show that after microglia replacement, the ALSP course is effectively halted. Together, microglia replacement corrects the pathogenic gene and thus halts the disease progress in the mouse model and human patients. This study strongly demonstrates clinical potentials of microglia replacement in neurological disease treatments.

neuroscience↗

bioRxiv2024

The Role of ADGRA3 in Adipose Thermogenesis: A Potential Therapeutic Target for Obesity

The induction of adipose thermogenesis plays a critical role in maintaining body temperature and improving metabolic homeostasis to combat obesity. {beta}3-adrenoceptor ({beta}3-AR) is widely recognized as a canonical {beta}-adrenergic G protein-coupled receptor (GPCR) that plays a crucial role in mediating adipose thermogenesis in mice. Nonetheless, the limited expression of {beta}3-AR in human adipocytes restricts its clinical application. The objective of this study was to identify a GPCR that is highly expressed in human adipocytes and to explore its potential involvement in adipose thermogenesis. Our research findings have demonstrated that the adhesion G protein-coupled receptor A3 (ADGRA3), an orphan GPCR, plays a significant role in adipose thermogenesis through its constitutively active effects. ADGRA3 exhibited high expression levels in human adipocytes and mouse brown fat. Furthermore, the knockdown of Adgra3 resulted in an exacerbated obese phenotype and a reduction in the expression of thermogenic markers. Conversely, Adgra3 overexpression activated the adipose thermogenic program and improved metabolic homeostasis without an exogenous ligand supplementation. We found that ADGRA3 facilitates the biogenesis of beige adipocytes through the Gs-PKA-CREB axis. Moreover, hesperetin was identified as a potential agonist of ADGRA3, capable of inducing adipocyte browning and ameliorating insulin resistance. In conclusion, our study demonstrated that the overexpression of constitutively active ADGRA3 or the activation of ADGRA3 by hesperetin can induce adipocyte browning by Gs-PKA-CREB axis. These findings indicate that the utilization of hesperetin and the selectively overexpression of ADGRA3 in adipose tissue could serve as promising therapeutic strategies in the fight against obesity.

cell biology↗

bioRxiv2024

Amygdala engages non-emotional multi-item working memory maintenance through amygdala-hippocampus interaction

Retaining information in working memory (WM) is an active process that requires neural activity within and between regions. The human amygdala (AMY) and hippocampus (HPC) are known to play crucial roles in WM processing. Although electrophysiological studies have revealed that the HPC supports multi-item maintenance in a load-dependent manner, the characteristics of the AMY and the circuit-level mechanisms underlying AMY-HPC interactions remain largely unexplored. To address this knowledge gap, intracranial EEG recordings from the AMY and HPC in nine epileptic patients were employed to evaluate intraregional neural representations and interregional communications during maintenance under different non-emotional WM loads. High load enhanced low-frequency power and intraregional theta-gamma phase-amplitude coupling (PAC) in the AMY and HPC. At the network level, a high load elicited an increase in the strength of the HPC theta phase modulation, which entrains the AMY gamma amplitude. Furthermore, a high load increased AMY-anterior HPC (aHPC) theta phase synchrony and directional connectivity strength from the aHPC to the AMY. Conversely, posterior HPC (pHPC)-AMY synchrony was not affected by load variations. Overall, these findings highlight the importance of the AMY in non-emotional WM tasks and provide new insights into the neurophysiological basis of AMY-HPC interactions during WM maintenance.

neuroscience↗

bioRxiv2024

Genome sequencing of 'Fuji' apple clonal varieties reveals evolutionary history and genetic mechanism of the spur-type morphology

Somatic variations arising during asexual reproduction can lead to the emergence of bud sports exhibiting advantageous traits, forming the basis for bud sport breeding in perennial plants. Here, we report a near-complete, fully phased genome assembly of Fuji apple, enabling comprehensive identification of somatic variants across 74 clonally propagated Fuji varieties. Phylogenetic analysis of Fuji sport varieties indicates that the emergence of spur-type and early maturation traits results from multiple independent formation events. A number of putative functional somatic variants are identified, including one spur-type specific deletion located in the promoter of the TCP transcription factor gene MdTCP11. DNA methylation level of the deletion-associated miniature inverted-repeat transposable element is lower in the spur-type varieties compared to the standard-type varieties, while the expression of MdTCP11 is significantly higher. Overexpression of MdTCP11 in apple decreases the plant height, highlighting its important role in the development of spur-type apple varieties. This study sheds light on the 80-year cloning history of Fuji and provides valuable candidate causative mutations for apple breeding.

plant biology↗

bioRxiv2024

Vesicle-mediated mitochondrial clearance underlies an actionable metabolic vulnerability in triple-negative breast cancer

Selective autophagy of mitochondria is known to promote survival and progression of cancer cells in various malignancies including triple-negative breast cancer (TNBC). Here, we aimed to identify the essential metabolic adaptations that support mitochondrial quality control with the goal to uncover actionable metabolic vulnerabilities with therapeutic potential. Using an integrated approach of proteomics and untargeted and stable-isotope resolved metabolomics, coupled with functional experimental analyses, we define an alternative mechanism to mitophagy enabled by an onco-metabolic program of heightened extracellular sphingomyelin salvaging in TNBC that facilitates extracellular vesicle (EV)-mediated intracellular clearance of mitochondrial damage. Targeting of the cancer cell sphingolipid onco-metabolic pathway via repurposing of eliglustat, a selective small molecule inhibitor of glucosylceramide synthase (UGCG), resulted in ceramide-induced lethal mitophagy and attenuated tumor growth and prolonged overall survival at clinically achievable doses in an orthotopic syngeneic mouse model of TNBC. Our study defines a mechanism of aberrant sphingolipid metabolism that underlies an actionable metabolic vulnerability for anti-cancer treatment.

cancer biology↗

bioRxiv2024

The Interplay Between Nutrition and the Midgut Microbiome of the Mosquito Aedes aegypti Reveals Putative Symbionts.

Blood meals are crucial for the reproductive cycle of Aedes aegypti and represent the means by which arboviruses are transmitted to its hematophagy hosts. It also has been postulated that feeding on blood may modulate the mosquito microbiome, but the compositional shifts in microbial diversity and function remain elusive. In this paper, we analyzed the modulation of the midgut microbiome in 60 females of Aedes aegypti throughout the digestive period, 12, 24, and 48 hours after blood or sugar meals using whole-genome shotgun sequencing. Microbial transstadial transmission between larvae and adults was also assessed. This approach provided a high coverage of the midgut metagenome, allowing microbial taxonomic assignments at the species level and gene-based functional profiling. Females at later hours post-feeding and larvae display low microbiome diversities and little evidence of transstadial transmission. However, a striking proliferation of Enterobacterales was observed during early hours of digestion in blood-fed mosquitoes. The compositional shift was concomitant with a predicted functional change in genes associated with carbohydrate and protein metabolism. The observed shifts in blood-fed females midguts are restored to a sugar-fed-like microbial profile after 48h, when blood digestion is completed. Conversely, as in all blood-fed females, a high abundance of the opportunistic human pathogen Elizabethkingia anophelis (Flavobacteriales) takes place in this post-digestion stage. This bacterial species has also been described as a symbiont of mosquitoes of the genus Anopheles (Culicidae). This work is the first report of the adaptation of the midgut microbiome of A. aegypti to a digestive role after a blood meal, at the expense of the proliferation of potential symbionts. Significance statementThe findings in this paper can contribute to a better understanding of the dynamics of the mosquito microbiome during digestion and its potential implications for host physiology and metabolism, also informing the future development of sustainable methods for insect-borne diseases control based on microbial components that might influence vectorial capacity and pathogen transmission by A. aegypti.

microbiology↗

bioRxiv2024

Transcranial Photobiomodulation on the Left Prefrontal Cortex Enhances Mandarin Chinese L1 and L2 Complex Sentence Processing Performances

This study investigated the causal effect of transcranial photobiomodulation (tPBM) over the left prefrontal cortex (LPFC) on syntactically complex Mandarin Chinese first language (L1) and second language (L2) sentence processing performances. Two (L1 and L2) groups of participants (thirty per group) were recruited to receive the double-blind, sham-controlled tPBM intervention, followed by the sentence processing, the verbal working memory (WM), and the visual WM tasks. Results revealed a consistent pattern for both groups: (a) tPBM enhanced sentence processing performance but not verbal WM and visual WM performance; (b) Participants with lower sentence processing performances under sham tPBM benefited more from active tPBM. Taken together, the current study substantiated that tPBM enhanced L1 and L2 sentence processing ability directly without verbal WM interference, and would serve as a promising and cost-effective noninvasive brain stimulation (NIBS) tool for future applications on upregulating the human language faculty. HighlightsO_LIThe first study that applies tPBM to (complex) sentence processing. C_LIO_LItPBM enhances sentence processing performances in both Mandarin L1 & L2 speakers. C_LIO_LItPBM directly enhances sentence processing without the interference of verbal WM. C_LIO_LIA causal role of LPFC for sentence processing through active tPBM. C_LIO_LIOpening up the promising application prospect for tPBM on sentence processing. C_LI

neuroscience↗

bioRxiv2024

Embryonic origins of forebrain oligodendrocytes revisited by combinatorial genetic fate mapping

Multiple embryonic origins give rise to forebrain oligodendrocytes (OLs), yet controversies and uncertainty exist regarding their differential contributions. We established intersectional and subtractional strategies to genetically fate map OLs produced by medial ganglionic eminence/preoptic area (MGE/POA), lateral/caudal ganglionic eminences (LGE/CGE) and dorsal pallium. We found that, contrary to the canonical view, LGE/CGE-derived OLs make minimum contributions to the neocortex and corpus callosum, but dominate piriform cortex and anterior commissure. Additionally, MGE/POA-derived OLs, instead of being entirely eliminated, make small but sustained contribution to cortex with a distribution pattern distinctive from those derived from the dorsal origin. Our study provides a revised and more comprehensive view of cortical and white matter OL origins, and established valuable new tools and strategies for future OL studies.

neuroscience↗