Biology subjects

Pan, H.

Publications and source records attributed to Pan, H..

98 records · Page 6Linked to original sources

bioRxiv2019

TMEM16F phospholipid scramblase mediates trophoblast fusion and placental development

Cell-cell fusion or syncytialization is fundamental to the reproduction, development and homeostasis of multicellular organisms. In addition to various cell-type specific fusogenic proteins, cell surface externalization of phosphatidylserine (PS), a universal eat-me signal in apoptotic cells, has been observed in different cell-fusion events. Nevertheless, molecular underpinnings of PS externalization and cellular mechanisms of PS-facilitated cell-cell fusion are unclear. Here we report that TMEM16F, a Ca2+-activated phospholipid scramblase (CaPLSase), plays an indispensable role in placental trophoblast fusion by translocating PS to the cell surface independent of apoptosis. Consistent with its essential role in trophoblast fusion, the placentas from TMEM16F-deficient mice exhibit deficiency in syncytialization, placental developmental defects and perinatal lethality. Our findings thus identify a cell-cell fusion mechanism by which TMEM16F CaPLSase-dependent externalization of PS serves as a critical cell fusion signal to facilitate trophoblast syncytialization and placental development.

cell biology↗

bioRxiv2018

Draft genome assembly and population genetics of an agricultural pollinator, the solitary alkali bee (Halictidae: Nomia melanderi)

Alkali bees (Nomia melanderi) are solitary relatives of the halictine bees, which have become an important model for the evolution of social behavior, but for which few solitary comparisons exist. These ground-nesting bees defend their developing offspring against pathogens and predators, and thus exhibit some of the key traits that preceded insect sociality. Alkali bees are also efficient native pollinators of alfalfa seed, which is a crop of major economic value in the United States. We sequenced, assembled, and annotated a high-quality draft genome of 299.6 Mbp for this species. Repetitive content makes up more than one-third of this genome, and previously uncharacterized transposable elements are the most abundant type of repetitive DNA. We predicted 10,847 protein coding genes, and identify 479 of these undergoing positive directional selection with the use of population genetic analysis based on low-coverage whole genome sequencing of 19 individuals. We found evidence of recent population bottlenecks, but no significant evidence of population structure. We also identify 45 genes enriched for protein translation and folding, transcriptional regulation, and triglyceride metabolism evolving slower in alkali bees compared to other halictid bees. These resources will be useful for future studies of bee comparative genomics and pollinator health research.

genomics↗

bioRxiv2018

In vivo assembly and trafficking of olfactory Ionotropic Receptors

lonotropic Receptors (IRs) are a large, divergent subfamily of ionotropic glutamate receptors(iGluRs), with roles in chemosensation, thermosensation and hygrosensation. Analogous to the synaptic targeting mechanisms of their iGluR ancestors, IRs are thought to form complexes of broadly-expressed co-receptors and selectively-expressed tuning receptors to localise to sensory cilia. While tuning receptors extracellular ligand-binding domain (LBD) defines sensory specificity, the role of this domain in co-receptors is unclear. We identify a coreceptor-specific sequence in the LBD, which contains a single N-glycosylation site. Combining molecular genetic and cell biological analyses, we show that this site is dispensable for assembly of IR complexes in olfactory sensory neurons, but essential for endoplasmic reticulum exit of some,but not all, IR complexes. Our data reveal an important role for the IR co-receptor LBD in control of intracellular transport, provide novel insights into the stoichiometry and assembly of IR complexes, and uncover an unexpected heterogeneity in the trafficking regulation of this sensory receptor family.

neuroscience↗

bioRxiv2018

Diagnostic Whole Exome Sequencing in Patients with Short Stature

Short stature is among the most common reasons for children being referred to the pediatric endocrinology clinics. The cause of short stature is broad, in which genetic factors play a substantial role, especially in primary growth disorders. However, identifying the molecular causes for short stature remains as a challenge because of the high heterogeneity of the phenotypes. Here, whole exome sequencing (WES) was used to identify the genetic causes of short stature with unknown etiology for 20 patients aged from 1 to 16 years old. The genetic causes of short stature were identified in 9 of the 20 patients, corresponding to a molecular diagnostic rate of 45%. Notably, in 2 of the 9 patients identified with genetic causes, the diagnosed diseases based on WES are different from the original clinical diagnosis. Our results highlight the clinical utility of WES in the diagnosis of rare, high heterogeneity disorders.

genetics↗

bioRxiv2018

Introduce a New Approach to Detect Genes Associated to Oral Squamous Cell Carcinoma

Oral squamous cell carcinoma (OSCC) represents the most frequent of all oral neoplasms in the world. Genetics plays an important role in the etiopathogenesis of OSCC. However, the investigation of the molecular mechanism of OSCC is still incomplete. In this article, we introduced a new approach to detect OSCC-associated genes, in which we not only compare mean difference, but also variance difference between cases and controls. Based on two OSCC datasets from Gene Expression Omnibus, we identified 456 differentially variable (DV) gene probes, in addition to 2,375 differentially expressed (DE) gene probes. There are 2,193 DE-only probes, 274 DV-only probes, and 182 DE-and-DV probes. DAVID functional analysis showed that genes corresponding to DE-only, DV-only, and DE-and-DV probes were enriched in different KEGG pathways, indicating they play different roles in OSCC. This new approach can be used to investigate the genetic risk factors for other complex human diseases.

genetics↗

bioRxiv2018

The Association between Alcohol Consumption and Telomere Length: A Meta-Analysis Focusing on Observational Studies

BackgroundBoth telomere length and alcohol consumption play important roles in carcinogenesis and biological age. Many efforts have been made to investigate the association between alcohol consumption and telomere length. However, no consensus has been reached yet.\n\nMethodsIn this article, we performed a meta-analysis to integrate the investigation results in the literature about the association between alcohol consumption and telomere length. After searching articles published between 2000 and 2016, 21 articles (including 27 analyses, total sample size 35,891) met our eligibility criteria.\n\nResultsWe found a significant association between alcohol consumption and telomere length (Fishers combined p-value = 3.52E-8 and Liptaks weighted p-value = 8.24E-3). We also found that the significance of the association between alcohol consumption and telomere length varies with study type (cohort, case-control, or cross-sectional) and study population (Europe, Asia, American, or Australia).\n\nConclusionsCombined evidence showed that alcohol consumption is associated with telomere length. The consistent quantifications of alcohol consumption and telomere length would benefit the future aggregation of the evidence from different studies.

cancer biology↗

bioRxiv2018

Epigenetic analysis identifies factors driving racial disparity in prostate cancer

Prostate cancer (PCa) is the second most leading cause of death in men worldwide. African American men (AA) represent more aggressive form of PCa as compared to Caucasian (CA) counterparts. Evidence suggests that genetic and other biological factors could account for the observed racial disparity. We analyzed the cancer genome atlas (TCGA) dataset (2015) for existing epigenetic variation in AA and CA prostate cancer patients, and carried out Reduced Representation Bisulphite Sequencing (RRBS) analysis to identify global methylation changes in AA and CA prostate cancer patients. The TCGA dataset analysis revealed that the epigenetic heterogeneity could be categorized into 4 classes, where AA associated primarily to methylation cluster 1 (p value 0.048), and CA associated to methylation cluster 3 (p value 0.000146). We identified enrichment of Wnt signaling genes in both AA and CA, however they were differentially activated in terms of canonical and non-canonical Wnt signaling pathway activation. This was further validated using the GenomeDx expression data. Our RRBS data also suggested distinct methylation patterns in AA compared to CA, and in part validated our TCGA findings. Survival analysis using the RRBS data suggested hypomethylated genes to be significantly associated with recurrence of prostate cancer in CA (p=6.07x10-6) as well as in AA (p=0.0077). Overall, the observed racial disparity in the molecular mechanism involved in the pathogenesis of prostate cancer suggests diverse heterogeneity that potentially could affect survival and should be considered during prognosis and treatment.

cancer biology↗

bioRxiv2017

The Nuclear And Mitochondrial Genomes Of The Facultatively Eusocial Orchid Bee Euglossa dilemma

Bees provide indispensable pollination services to both agricultural crops and wild plant populations, and several species of bees have become important models for the study of learning and memory, plant-insect interactions and social behavior. Orchid bees (Apidae: Euglossini) are especially important to the fields of pollination ecology, evolution, and species conservation. Here we report the nuclear and mitochondrial genome sequences of the orchid bee Euglossa dilemma Bembe & Eltz. Euglossa dilemma was selected because it is widely distributed, highly abundant, and it was recently naturalized in the southeastern United States. We provide a high-quality assembly of the 3.3 giga-base genome, and an official gene set of 15,904 gene annotations. We find high conservation of gene synteny with the honey bee throughout 80 million years of divergence time. This genomic resource represents the first draft genome of the orchid bee genus Euglossa, and the first draft orchid bee mitochondrial genome, thus representing a valuable resource to the research community.

genomics↗