Biology subjects

Wang, B.-J.

Publications and source records attributed to Wang, B.-J..

5 recordsLinked to original sources

bioRxiv2026

Regulatory divergence and effector turnover shape species-specific bacterial clearance in Drosophilidae

Innate immunity has been dissected in exquisite detail in Drosophila melanogaster, yet how immune systems diversify between species remains largely unknown. Here we compare responses to bacterial infection across five drosophilid species spanning 60 million years of divergence, from D. melanogaster to Scaptodrosophila lebanonensis. Seven-day survival after Gram-negative infection ranges from 19% to 99% and tracks inversely with bacterial load in a phylogenetically corrected model, indicating that clearance rather than tolerance drives these differences. RNA sequencing of all five species after sterile wounding or infection reveals strongly species-biased transcriptional responses to the same pathogen, together with numerous uncharacterized lineage-restricted genes, including predicted antimicrobial peptides. We chemically synthesized candidate peptides and confirmed their activity in vitro: Athelas (CG43920), Mtkl and the S. lebanonensis-specific Athelas-like are active against bacteria and fungi, while Daisho2, previously described as antifungal, also kills Gram-positive and Gram-negative bacteria. De novo assembly and machine-learning prediction recover further candidate peptides from intronic and intergenic regions missed by current annotation. Rewiring of conserved genes and turnover of young, often unannotated effectors therefore act together to diversify antibacterial defense within a single insect family.

evolutionary biology↗

bioRxiv2024

Gene regulatory networks and essential transcription factors for de novo originated genes

The regulation of gene expression is crucial for the functional integration of evolutionarily young genes, particularly those that emerge de novo. However, the regulatory programs governing the expression of de novo genes remain unknown. To address this, we applied computational methods to single-cell RNA sequencing data, identifying key transcription factors likely instrumental in regulating de novo genes. We found that transcription factors do not have the same propensity for regulating de novo genes; some transcription factors contain more de novo genes than others in their regulon. Leveraging genetic and genomic tools in Drosophila, we further examined the role of two key transcription factors and the regulatory architecture of novel genes. Our findings identify key transcription factors associated with the expression of de novo genes and provide new insights into how modifications in existing transcription factors enable the emergence, maintenance, and regulation of de novo genes.

evolutionary biology↗

bioRxiv2024

Identification of a specialized lipid barrier for Drosophila metamorphosis

In many terrestrial insects, the onset of metamorphosis marks a transition from humid to dry environments. Yet how metamorphosing insect pupae protect themselves against the threat of dehydration remains unclear. Here, we identify the chemical composition and biosynthetic origins of a lipid desiccation barrier specific to the pupal and sexually-immature adult stages of Drosophila melanogaster. This barrier comprises unisex hyper-long hydrocarbons, 29-37 carbons in length, which are synthesized by larval oenocytes and stored in the larval fat body before being deployed on the pupal and young adult cuticles. We show that the fatty acid elongase EloHL is required for the biosynthesis of hyper-long hydrocarbons that are essential for the barrier to water loss during metamorphosis. Across the Drosophila genus, many species express unisex profiles of hyper-long hydrocarbons and, as young adults, transition to sex-specific shorter hydrocarbons with known pheromonal functions. The desert species D. mojavensis, however, retains hyper-long hydrocarbons during adulthood likely as an adaptation to an arid environment. Our study reveals how the cuticular lipid barrier is tuned to meet changing environmental pressures during insect development and evolution.

developmental biology↗

bioRxiv2023

Pannexin 1 modulates angiogenic activities of human endothelial colony-forming cells through IGF-1 mechanism and is a marker of senescence

BACKGROUNDWe examined the role of pannexins in human endothelial progenitor cell (EPC) senescence. METHODSYoung and replication-induced senescent endothelial colony-forming cells (ECFCs) derived from human circulating EPCs were used to examine cellular activities and senescence-associated indicators after transfection of siRNA specific to Panx1 or lentivirus-mediated Panx1 overexpression. Hindlimb ischemia mice were used as in vivo angiogenesis model. Protein and phospho-kinase arrays were used to determine underlying mechanisms. RESULTSPanx1 was the predominant pannexin isoform in human ECFCs and up-regulated in both replication-induced senescent ECFCs and circulating EPCs from aged mice and humans. Cellular activities of the young ECFCs were enhanced by Panx1 down-regulation, but attenuated by its up-regulation. In addition, reduction of Panx1 in the senescent ECFCs could rejuvenate cellular activities with reduced senescence-associated indicators, including senescence-associated {beta}-galactosidase activity, p16INK4a, p21, acetyl-p53, and phospho-Histone H2A.X. In mouse ischemic hindlimbs injected senescent ECFCs, blood perfusion ratio, salvaged limb outcome, and capillary density were all improved by Panx1 knockdown. Insulin-like growth factor 1 (IGF-1) was significantly increased in the supernatant from senescent ECFCs after Panx1 knockdown. The enhanced activities and paracrine effects of Panx1 knockdown senescent ECFCs were completely inhibited by anti-IGF-1 antibodies. FAK, ERK and STAT3 were activated in senescent ECFCs with Panx1 knockdown, in which the intracellular calcium level was reduced, and the activation was inhibited by supplemented calcium. The increased IGF-1 in Panx1-knockdown ECFCs was abrogated respectively by inhibitors of FAK (PF562271), ERK (U0126), and STAT3 (NSC74859), and supplemented calcium. CONCLUSIONSPanx1 expression is up-regulated in human ECFCs/EPCs with replication-induced senescence and during aging. Angiogenic potential of senescent ECFCs is improved by Panx1 reduction through increased IGF-1 production via activation of FAK-ERK axis following calcium influx reduction. Our findings provide new strategies to evaluate EPC activities and rejuvenate senescent EPCs for therapeutic angiogenesis.

cell biology↗

bioRxiv2020

Many bat species are not potential hosts of SARS-CoV and SARS-CoV-2: Evidence from ACE2 receptor usage

Bats are the suggested natural hosts for severe acute respiratory syndrome coronavirus (SARS-CoV) and SARS-CoV-2, the latter of which caused the coronavirus disease 2019 (COVID-19) pandemic. The interaction of viral Spike proteins with their host receptor angiotensin-converting enzyme 2 (ACE2) is a critical determinant of potential hosts and cross-species transmission. Here we use virus-host receptor binding and infection assays to show that ACE2 orthologs from 24, 21, and 16 of 46 phylogenetically diverse bat species - including those in close and distant contact with humans - do not support entry of SARS-CoV, SARS-CoV-2, and both of these coronaviruses, respectively. Furthermore, we used genetic and functional analyses to identify genetic changes in bat ACE2 receptors associated with viral entry restrictions. Our study demonstrates that many - if not most - bat species are not potential hosts of SARS-CoV and SARS-CoV-2, and provides important insights into pandemic control and wildlife conservation.

ecology↗