Biology subjects

Fan, P.

Publications and source records attributed to Fan, P..

At least 19 recordsLinked to original sources

bioRxiv2026

WUSCHEL modulates jasmonate signaling to control the balance between growth and defense in the shoot apical meristem

The growth-defense trade-off is an essential survival strategy for plants under environmental stress. However, how this balance is maintained at the meristematic level remains unclear. Here, we show that wounding of rosette leaves systemically inhibits inflorescence stem growth, associated with reduced cell proliferation in the inner cell layers of the shoot apical meristem (SAM), but not in the apical stem cell domain. Mechanistically, this selective cell behavior is dependent on the interplay between the growth-repressing jasmonate (JA) signaling and the growth-promoting stem cell regulator WUSCHEL (WUS). WUS mitigates wounding-induced growth inhibition by repressing JA-responsive gene expression via promoting the accumulation of JASMONATE-ZIM DOMAIN 3 (JAZ3), which encodes a JA signaling repressor. WUS on the one hand induces JAZ3 mRNA accumulation and on the other hand directly competes with the JA receptor CORONATINE INSENSITIVE1 (COI1) for JAZ3 binding, thereby inhibiting JAZ3 protein degradation. Our findings identify a WUS-JAZ3-COI1 regulatory module that coordinates the growth-defense balance in the SAM upon systemic wounding, revealing a cell-type-specific mechanism for sustaining developmental robustness of the meristem during stress response.

plant biology↗

bioRxiv2025

Genomic Evidence for Males of Exceptional Reproductive Output (ERO) in Apes and Humans

It is widely suspected that a small percentage of males have exceptional reproductive output (ERO) but progeny numbers of males are rarely measurable, even in humans. If we define the variance ratio of reproductive-output in males and females as = VM/VF, the ERO hypothesis would predict >>1. Since autosomal, X, and Y chromosomes are found in males 1/2, 1/3, and 100% of the time, their DNA diversities can inform about . For example, autosomal and Y-linked diversities are governed, respectively, by (VM+VF)/2 and VM. When comparing the chromosomal diversities, appears to be near 20 for chimpanzees and orangutans, and 1-10 for gorillas. The exception is bonobos with < 1. In humans, the extensive genomic data are coupled to a theory, developed herein, that can filter out selection influences on Y-linked diversities. Hence, the estimation of is rigorous, yielding values near or above 20, depending on the population. When >10, the presence of ERO males is very likely. These analyses can be applied more generally to species with XY sex determination.

evolutionary biology↗

bioRxiv2025

Multimodal brain cell atlas across the adult macaque lifespan

High-throughput single-cell omics of non-human primate tissues present a remarkable opportunity to study primate brain aging. Here, we introduce a transcriptomic and chromatin accessibility landscape of 1,985,317 cells from eight brain regions of 13 cynomolgus female monkeys spanning adult lifespan including exceptionally old individuals up to 29-years old. This dataset uncovers dynamic molecular changes in critical brain functions such as synaptic communication and axon myelination, exhibiting a high degree of cell type and brain region specificity. We identify the multicellular networks of the pons and medulla as a previously unrecognized hotspot for aging. Furthermore, comparative analyses with human neurodegeneration datasets highlight both shared and distinct mechanisms contributing to aging and disease. In addition, we uncover transcription factors implicated in monkey brain aging and pinpoint aging-regulated loci linked to longevity and neurodegeneration. This spatiotemporal atlas will advance our understanding of primate brain aging and its broader implications for health and disease.

neuroscience↗

bioRxiv2024

Early-life antibiotic exposure leads to gut microbial dysbiosis associated with neurodevelopment and neuroregeneration

Early-life is a critical period for neurodevelopment and establishment of gut microbiota, which are highly susceptible to antibiotic exposure. Here, we aimed to investigate association between gut microbiota and metabolites with neurodevelopment and neuroregeneration in early-life after antibiotic exposure. To induce microbial dysbiosis in offspring, a broad-spectrum antibiotic cocktail was administered to mice dams. The prefrontal lobe, spinal cord tissues and gut sample of offspring were collected at different time with or without spinal cord crush injury. 16S rRNA sequencing and metabolomics were performed to analyze the gut microbiota and metabolites. NG2 glia were cultured and treated by mitochondrial fusion and fission compounds and metabolites. Maternal antibiotic exposure significantly affected neuronal maturation, NG2 glia proliferation, prefrontal cortex myelination and injured spinal cord neuroregeneration of offspring. Mice in antibiotic exposure group exhibited disruption of gut microbiota and metabolites, along with lower Ace, Chao and Shannon indexes, higher relative abundance of Enterobacter and Escherichia_Shigella, lower lactobacillus and Streptococcus genus, and downregulated Cyclo(Arg-Gly-Asp-D-Phe-Val), Ampicilloyl, DG(8:0/i-19:0/0:0), Petasinine and 6-Hydroxymelatonin glucuronide. These metabolites were enriched in alpha-Linolenic acid metabolism, phenylalanine, tyrosine and tryptophan biosynthesis, linoleic acid metabolism. 6-Hydroxymelatonin glucuronide, PC(20:3/0:0), PC(20:2/0:0), Ameltolide, DG(8:0/i-19:0/0:0), Inproquone, and Chorismate were the cores of networks between gut microbiota and metabolites and negatively associated with neurodevelopment and neuroregeneration. Additionally, gut microbiota metabolites promoted NG2 glia differentiation, partly through reversing the effects of mitochondrial fusion/fission compounds. Totally, antibiotic exposure in early-life changed the composition, abundance, and metabolites of gut microbiota in offspring, which was associated with neurodevelopment and neuroregeneration.

microbiology↗

bioRxiv2024

Predictive power of different Akkermansia phylogroups in clinical response to PD-1 blockade against non-small cell lung cancer

Immune checkpoint blockade has emerged as a promising form of cancer therapy. However, only some patients respond to checkpoint inhibitors, while a significant proportion of patients do not, calling for the discovery of reliable biomarkers. Recent studies reported the importance of the gut microbiome in the clinical response to PD-1 blockade against non-small cell lung cancer (NSCLC), highlighting Akkermansia muciniphila as a candidate biomarker. Motivated by the genomic and phenotypic differences across Akkermansia muciniphila strains and Akkermansia (Akk) phylogroups (AmIa, AmIb, AmII, AmIII and AmIV), we analyzed fecal metagenomic sequencing data from four publicly available NSCLC cohorts (n = 575). Encouragingly, we found that patients responses to PD-1 blockade are significantly different across different Akk phylogroups, highlighting the relatively stronger association between AmIa and positive responses than the other phylogroups. Importantly, we also highlight the importance of considering the clinical heterogeneity among independent cohorts in across validation analysis. We built a machine learning model based on Akk gene profiles, which shed light on a group of Akk genes that may be associated with the response to PD-1 blockade. In summary, our study underlines the benefits of high-resolution analysis of Akk genomes in the search for biomarkers that may improve the prediction of patients responses to cancer immunotherapy.

genomics↗

bioRxiv2023

Dorsal hippocampal oxytocin receptor regulates adult peer bonding in rats

Healthy social relationships are beneficial whereas their breakdown is often linked to psychiatric disorders. Parental care and bonding between sexual partners have been well studied both at the level of behavioral analysis and underlying neuronal mechanisms. By contrast, little is known about the neural and molecular basis of peer bonding, defined as social bonds formed between unrelated individuals of the same sex, due to the lack of a suitable experimental paradigm. We found that adult Sprague Dawley (SD) rats of the same sex form strong peer bonds with each other following co-housing. Peer bonded rats exhibit affiliative displays toward their cagemates who are distressed whereas they exhibit agonistic behaviors toward strangers in these situations. Using innovative, genetic strategies in rats, we show that both oxytocin receptor (OXTR) bearing neurons and Oxtr signaling in the dorsal hippocampus are essential for peer bonds to form. Together, we have developed a new platform for studying peer bonding and demonstrate a neural pathway that governs this behavior.

neuroscience↗

bioRxiv2023

Nitric Oxide controls shoot meristem activity via regulation of DNA methylation

Despite the importance of Nitric Oxide (NO) as signaling molecule in both plant and animal development1-7, the regulatory mechanisms downstream of NO remain largely unclear. Here, we show that NO is involved in Arabidopsis shoot stem cell control via modifying expression and activity of ARGONAUTE 4 (AGO4), a core component of the RNA directed DNA Methylation (RdDM) pathway. Mutations in components of the RdDM pathway cause meristematic defects, and reduce responses of the stem cell system to NO signaling. Importantly, we found that the stem cell inducing WUSCHEL transcription factor directly interacts with AGO4 in an NO dependent manner, explaining how these two signaling systems may converge to modify DNA methylation patterns. Taken together, our results reveal that NO signaling plays an important role in controlling plant stem cell homeostasis via the regulation of de novo DNA methylation.

plant biology↗

bioRxiv2023

Haplotype-phased genome revealed the butylphthalide biosynthesis and hybrid origin of Ligusticum chuanxiong

Butylphthalide, one type of phthalides, is one of the first-line drugs for ischemic stroke therapy, while no enzyme involved in its biosynthesis pathway has been reported. Here, we present the first haplotype-resolved genome of Ligusticum chuanxiong Hort., a long-cultivated and phthalide-rich medicinal plant in Apiaceae. Based on comprehensive candidate gene screening, four Fe (II)- and 2-oxoglutarate-dependent dioxygenases (2OGDs) and two CYPs were mined and further biochemically verified as phthalide C-4/C-5 desaturase (P4,5Ds) that converts senkyunolide A to l-n-butylphthalide (l-NBP) and ligustilide to butylidenephthalide. The substrate promiscuity and functional redundancy featured for P4,5Ds may contribute to the high phthalide diversity in L. chuanxiong. Notably, comparative genomic evidence supported L. chuanxiong as a diploid hybrid with L. sinense as a potential parent. The two haplotypes demonstrated exceptional structure variance and diverged around 3.42 million years ago (Ma). Our study is an icebreaker for the dissection of phthalide biosynthesis pathway and reveals the hybrid origin of L. chuanxiong. These findings will facilitate the future metabolic engineering for l-NBP production and breeding efforts for L. chuanxiong.

synthetic biology↗

bioRxiv2023

Phylogenomics reveals pervasive ancient introgression in the radiation of macaques

The genus Macaca, with 23 species assigned into four to seven species groups, exhibits the largest geographic range and represents the most successful adaptive radiation of nonhuman primates. Here, we conducted phylogenomic analyses of 16 newly generated and eight published macaque genomes and found a strong support for the division of this genus into seven species groups. Both ancient hybrid and incomplete lineage sorting (ILS) have contributed to the radiation and evolution of macaques. Particularly, the contradicting phylogenetic positions among silenus/nigra, fascicularis/mulatta and arctoides/sinica lineages were likely resulted from high level of ILS and potential hybridization between the ancestors of the arctoides/sinica and silenus/nigra lineages. Furthermore, an integrated scenario for macaque radiation is reconstructed by the help of the dated phylogenetic tree combined with documented history records. This study provides insights into ancient introgression involved in the radiation of macaques, which may help us to understand the rapid speciation of nonhuman primates.

evolutionary biology↗

bioRxiv2022

A plant virus causes symptoms through the deployment of a host-mimicking protein domain to attract the insect vector

Viruses are obligate intracellular parasites with limited proteomes that heavily rely on the cell molecular machinery for their multiplication and spread. Plant viruses frequently cause symptoms through interference with host developmental programs. Despite the agricultural relevance of symptom development in virus-infected crops, the molecular mechanisms underlying these viral effects remain elusive. Here, we show that the symptoms triggered by tomato yellow leaf curl virus (TYLCV) depend on the physical interaction between the host-mimicking domain of a virus-encoded protein, C4, and a plant-specific family of RCC1-like domain-containing (RLD) proteins. C4 outcompetes endogenous interactors of RLDs, disrupting RLD function in the regulation of endomembrane trafficking and polar auxin transport, ultimately leading to the developmental alterations recognized as symptoms of the viral infection. Importantly, symptoms do not have a detectable effect on the performance of the virus in the plant host, but they serve as attractants for the viral insect vector, the whitefly Bemisia tabaci, hence promoting pathogen spread. Our work uncovers the molecular underpinnings of the viral manipulation that leads to symptom development in the TYLCV-tomato pathosystem, and suggests that symptoms have evolved as a strategy to promote viral transmission by the insect vector. Given that most plant viruses are insect-transmitted, the principles described here might have broad applicability to crop-virus interactions.

plant biology↗

bioRxiv2021

Cell transcriptomic atlas of the non-human primate Macaca fascicularis

Studying tissue composition and function in non-human primates (NHP) is crucial to understand the nature of our own species. Here, we present a large-scale single-cell and single-nucleus transcriptomic atlas encompassing over one million cells from 43 tissues from the adult NHP Macaca fascicularis. This dataset provides a vast, carefully annotated, resource to study a species phylogenetically close to humans. As proof of principle, we have reconstructed the cell-cell interaction networks driving Wnt signalling across the body, mapped the distribution of receptors and co-receptors for viruses causing human infectious diseases and intersected our data with human genetic disease orthologous coordinates to identify both expected and unexpected associations. Our Macaca fascicularis cell atlas constitutes an essential reference for future single-cell studies in human and NHP.

cell biology↗

bioRxiv2021

Effects of Guangzhou seasonal climate change on the development of Aedes albopictus and its susceptibility to DENV-2

The susceptibility of Asian tiger mosquitoes to DENV-2 in different seasons was observed in simulated field environments as a reference to design dengue fever control strategies in Guangzhou. The life table experiments of mosquitoes in four seasons were carried out in the field. The susceptibility of Ae. albopictus to dengue virus was observed in both environments in Guangzhou in summer and winter. Ae. albopictus was infected with dengue virus by oral feeding. On day 7 and 14 after infection, the viral load in the head, ovary, and midgut of the mosquito was detected using real-time fluorescent quantitative PCR. Immune-associated gene expression in infected mosquitoes was performed using quantitative real-time reverse transcriptase PCR. The hatching rate and pupation rate of Ae. albopictus larvae in different seasons differed significantly. The winter hatching rate of larvae was lower than that in summer, and the incubation time was longer than in summer. In the winter field environment, Ae. albopictus still underwent basic growth and development processes. Mosquitoes in the simulated field environment were more susceptible to DENV-2 than those in the simulated laboratory environment. In the midgut, viral RNA levels on day 7 in summer were higher than those on day 7 in winter (F = 14.459, P = 0.01); ovarian viral RNA levels on day 7 in summer were higher than those on day 7 in winter (F = 8.656, P < 0.001), but there was no significant difference in the viral load at other time points (P > 0.05). Dicer-2 mRNA expression on day 7 in winter was 4.071 times than that on day 7 in summer: the viral load and Dicer-2 expression correlated moderately. Ae. albopictus could still develop and transmit dengue virus in winter in Guangzhou. Mosquitoes under simulated field conditions were more susceptible to DENV-2 than those under simulated laboratory conditions. Author summaryAe. albopictus is the only vector of dengue fever in Guangzhou. Observational data of Ae. albopictus development under natural conditions is important for monitoring vector population expansion, dengue virus transmission, and disease outbreak prevention. We found that Ae. albopictus could still develop in winter in Guangzhou. In addition, the viral load of mosquitoes in the simulated winter environment was lower than that in summer on the 7th day after infection; however, the difference in the viral load of mosquitoes in winter and summer on the 14th day after infection was not statistically significant. Mosquitoes in simulated field conditions were more susceptible to DENV-2 than those in simulated laboratory conditions. The results suggested that Ae. albopictus retains the ability to transmit dengue virus in winter in Guangzhou, and that improved dengue epidemic prevention and control measures are required. The findings of this study represent an important reference for the design of dengue fever control strategies in Guangzhou in response to global climate change.

ecology↗

bioRxiv2021

Combinatorial interactions between viral proteins expand the functional landscape of the viral proteome

As intracellular parasites, viruses need to manipulate the molecular machinery of their host cells in order to enable their own replication and spread. This manipulation is based on the activity of virus-encoded proteins. The reduced size of viral genomes imposes restrictions in coding capacity; how the action of the limited number of viral proteins results in the massive cell reprogramming observed during the viral infection is a long-standing conundrum in virology. In this work, we explore the hypothesis that combinatorial interactions expand the multifunctionality of viral proteins, which may exert different activities individually and when in combination, physical or functional. We show that the proteins encoded by a plant-infecting DNA virus physically associate with one another in an intricate network. Our results further demonstrate that these interactions can modify the subcellular localization of the viral proteins involved, and that co-expressed interacting viral proteins can exert novel biological functions in planta that go beyond the sum of their individual functions. Based on this, we propose a model in which combinatorial physical and functional interactions between viral proteins enlarge the functional landscape of the viral proteome, which underscores the importance of studying the role of viral proteins in the context of the infection.

plant biology↗

bioRxiv2021

Thinopyrum intermedium TiAP1 interacts with a chitin deacetylase from Blumeria graminis f. sp. tritici and increases the resistance to Bgt in wheat

The biotrophic fungal pathogen Blumeria graminis f. sp. tritici (Bgt) is a crucial factor causing reduction of global wheat production. Wild wheat relatives, e.g. Thinopyrum intermedium, is one of the wild-used parents in wheat disease-resistant breeding. From T. intermedium line, we identified the aspartic acid protein gene, TiAP1, which involved in resistance against Bgt. TiAP1 is a secreted protein that accumulates in large amounts at the infection sites of powdery mildew and extends to the intercellular space. Yeast two-hybrid showed that it interacted with the chitin deacetylase (BgtCDA1) of Bgt. The yeast expression, purification, and invitro test confirmed the chitin deacetylase activity of BgtCDA1. The bombardment and VIGS mediated host-induced gene silencing showed BgtCDA1 promotes the invasion of Bgt. Transcriptome analysis showed the cell wall xylan metabolism, lignin biosynthesis-related, and defence genes involved in the signal transduction were upregulated in the transgenic TiAP1 wheat induced by Bgt. The TiAP1 in wheat may inactivate the deacetylation function of BgtCDA1, cause chitin oligomers expose to wheat chitin receptor, then trigger the wheat immune response to inhibit the growth and penetration of Bgt, and thereby enhance the tolerance of wheat to pathogens.

plant biology↗

bioRxiv2020

A potent neutralizing human antibody reveals the N-terminal domain of the Spike protein of SARS-CoV-2 as a site of vulnerability

The pandemic of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) presents a global public health threat. Most research on therapeutics against SARS-CoV-2 focused on the receptor binding domain (RBD) of the Spike (S) protein, whereas the vulnerable epitopes and functional mechanism of non-RBD regions are poorly understood. Here we isolated and characterized monoclonal antibodies (mAbs) derived from convalescent COVID-19 patients. An mAb targeting the N-terminal domain (NTD) of the SARS-CoV-2 S protein, named 4A8, exhibits high neutralization potency against both authentic and pseudotyped SARS-CoV-2, although it does not block the interaction between angiotensin-converting enzyme 2 (ACE2) receptor and S protein. The cryo-EM structure of the SARS-CoV-2 S protein in complex with 4A8 has been determined to an overall resolution of 3.1 Angstrom and local resolution of 3.4 Angstrom for the 4A8-NTD interface, revealing detailed interactions between the NTD and 4A8. Our functional and structural characterizations discover a new vulnerable epitope of the S protein and identify promising neutralizing mAbs as potential clinical therapy for COVID-19.

biochemistry↗

bioRxiv2020

Targeted genome editing in Nicotiana tabacum using inducible CRISPR/Cas9 system

Targeted genome editing has been achieved in multiple plant species using the clustered regularly interspaced short palindromic repeats (CRISPR)-associated protein 9 (CRISPR/Cas9) system, in which the Cas9 gene is usually driven by constitutive promoters. However, constitutive expression of Cas9 is not necessary and can be harmful to plant development. In this study, we developed an estrogen-inducible CRISPR/Cas9 system by taking advantage of the chimeric transcription activator XVE and tested the efficacy of this inducible system in Nicotiana tabacum by targeting the phytoene desaturase (NtPDS) gene, whose mutation resulted in albino phenotypes. Treatment of four independent transgenic lines with exogenous estradiol successfully induced targeted mutagenesis in NtPDS. Sanger sequencing assay uncovered the presence of indel mutations (nucleotides insertions or deletions) at the target site as expected, and at least two types of mutations were identified for each line. Transgenic plants with mutated NtPDS gene after estradiol treatment exhibited pale green or incomplete albino leaves. Moreover, the expression of Cas9 in transgenic plants was strongly induced by estradiol treatment. Our results demonstrate the efficacy of XVE-based CRISPR/Cas9 system in N. tabacum, and the system reported here promises to be a useful approach for conditional genome editing, which would facilitate the study of genes of interest, especially those developmentally important genes.

plant biology↗

bioRxiv2020

Evolution of a plant gene cluster in Solanaceae and emergence of metabolic diversity

Plants produce phylogenetically and spatially restricted, as well as structurally diverse specialized metabolites via multistep metabolic pathways. Hallmarks of specialized metabolic evolution include enzymatic promiscuity, recruitment of primary metabolic enzymes and genomic clustering of pathway genes. Solanaceae plant glandular trichomes produce defensive acylsugars, with aliphatic sidechains that vary in length across the family. We describe a tomato gene cluster on chromosome 7 involved in medium chain acylsugar accumulation due to trichome specific acyl-CoA synthetase and enoyl-CoA hydratase genes. This cluster co-localizes with a tomato steroidal alkaloid gene cluster forming a supercluster, and is syntenic to a chromosome 12 region containing another acylsugar pathway gene. We reconstructed the evolutionary events leading to emergence of this gene cluster and found that its phylogenetic distribution correlates with medium chain acylsugar accumulation across the Solanaceae. This work reveals dynamics behind emergence of novel enzymes from primary metabolism, gene cluster evolution and cell-type specific metabolite diversity.

plant biology↗

bioRxiv2020

Within and cross species predictions of plant specialized metabolism genes using transfer learning

Plant specialized metabolites mediate interactions between plants and the environment and have significant agronomical/pharmaceutical value. Most genes involved in specialized metabolism (SM) are unknown because of the large number of metabolites and the challenge in differentiating SM genes from general metabolism (GM) genes. Plant models like Arabidopsis thaliana have extensive, experimentally derived annotations, whereas many non-model species do not. Here we employed a machine learning strategy, transfer learning, where knowledge from A. thaliana is transferred to predict gene functions in cultivated tomato with fewer experimentally annotated genes. The first tomato SM/GM prediction model using only tomato data performs well (F-measure=0.74, compared with 0.5 for random and 1.0 for perfect predictions), but from manually curating 88 SM/GM genes, we found many mis-predicted entries were likely mis-annotated. When the SM/GM prediction models built with A. thaliana data were used to filter out genes where the A. thaliana-based model predictions disagreed with tomato annotations, the new tomato model trained with filtered data improved significantly (F-measure=0.92). Our study demonstrates that SM/GM genes can be better predicted by leveraging cross-species information. Additionally, our findings provide an example for transfer learning in genomics where knowledge can be transferred from an information-rich species to an information-poor one.

plant biology↗