Biology subjects

He, Z.

Publications and source records attributed to He, Z..

298 records · Page 17Linked to original sources

bioRxiv2018

Cyclin B3 is specifically required for metaphase to anaphase transition in mouse oocyte meiosis I

Meiosis, a cell division to generate gametes for sexual reproduction in eukaryotes, executes a single round of DNA replication and two successive rounds of chromosome segregation [1]. The extraordinary reliability of the meiotic cycle requires the activities of cyclin-dependent kinases (Cdks) associated with specific cyclins [2-4]. Cyclins are the regulatory subunits of protein kinases, which are the main regulators of maturation promoting factor or mitosis promoting factor (MPF) [5, 6] and anaphase-promoting complex/cyclosome (APC/C) [7, 8] in eukaryotic cell division. But how cyclins collaborate to control meiosis is still largely unknown. Cyclin B3 (Ccnb3) shares homology with A- and B-type cyclins [9], and is conserved during higher eukaryote evolution [10-17]. Previous studies have shown that Ccnb3-deleted females are sterile with oocytes unable to complete meiosis I in Drosophila [18], implying that Ccnb3 may have a special role in meiosis. To clarify the function of Ccnb3 in meiosis in mammalian species, we generated Ccnb3 mutant mice by CRISPR/Cas9, and found that Ccnb3 mutation caused female infertility with the failure of metaphase-anaphase transition in meiosis I. Ccnb3 was necessary for APC/C activation to initiate anaphase I, but not required for oocytes maturation, meiosis II progression, or early embryonic development. Our study reveals the differential cell cycle regulation between meiosis I and meiosis II, as well as meiosis between males and females, which shed light on the cell cycle control of meiosis.\n\nHighlightsO_LIIdentification of a female meiosis-specific cyclin in mouse\nC_LIO_LICyclin B3 is required for metaphase-anaphase transition in oocyte meiosis I\nC_LIO_LICyclin B3 is not essential for oocyte maturation and sister chromosome segregation\nC_LIO_LICyclin B3 is necessary for APC/C activation and MPF kinase activity through Cdk1\nC_LI

cell biology↗

bioRxiv2018

Interleukin 22 mediates interleukin 23-induced pathology in newborn mice by disrupting the function of intestinal and pancreatic cells

Mice expressing IL-23 constitutively in the intestine or skin fail to grow and die prematurely. These phenotypes are associated with marked changes in the levels of circulating cytokines and with changes in the transcriptome of the pancreas and intestine. Marked changes are observed in the expression of molecules involved in digestion and absorption of carbohydrates, proteins, and lipids, resulting in a malabsorptive condition. Genetic ablation of IL-22, or one of the subunits of the IL-22R in mice expressing IL-23, restores normal growth and increases the life span of the animals. Mechanistically, IL-22 acts directly at the level of pancreatic acinar cells to decrease expression of the pancreas associated transcription factor 1a (Ptfla), an important transcription factor controlling expression of genes encoding pancreatic enzymes, and acinar cell identity. The results indicate that dysregulated expression of IL-23 and IL-22 has severe consequences in newborns and reveal an unsuspected role for IL-22 in controlling pancreatic enzyme secretion and food absorption.

immunology↗

bioRxiv2018

Enhanced Synthesis of Poly Gamma Glutamic Acid by Increasing the Intracellular Reactive Oxygen Species in the Bacillus licheniformis Δ1-pyrroline-5-carboxylate Dehydrogenase Gene ycgN Deficient Strain

Poly gamma glutamic acid ({gamma}-PGA) is an anionic polyamide with numerous applications. Proline metabolism influences the formation of reactive oxygen species (ROS), and is involved in a wide range of cellular processes. However, the relation between proline metabolism and{gamma} -PGA synthesis has not yet been analyzed. In this study, our results indicated that the deletion of {Delta}1-pyrroline-5-carboxylate dehydrogenase encoded gene ycgN resulted in 85.22% higher yield of{gamma} -PGA in B. licheniformis WX-02. But the deletion of proline dehydrogenase encoded gene ycgM had no effect on{gamma} -PGA synthesis. Meanwhile, a 2.92-fold higher level of P5C was detected in ycgN deficient strain WX{Delta}ycgN, while the P5C levels in WX{Delta}ycgM and double mutant strain WX{Delta}ycgMN remained the same, compared to WX-02. The ROS level of WX{Delta}ycgN was 1.18-fold higher than that of WX-02, and the addition of n-acetylcysteine (antioxidant) into medium could decrease its ROS level, further reduced the{gamma} -PGA yield. Our results showed that proline catabolism played an important role in maintaining ROS homeostasis, and the deletion of ycgN caused P5C accumulation, which induced a transient ROS signal to promote{gamma} -PGA synthesis in B. licheniformis.\n\nImportance{gamma}-PGA is an anionic polyamide with various applications in biomedical and industrial fields. Proline metabolism influences the intracellular reactive oxygen species (ROS) and is involved in a wide range of cellular processes. Here, we report the effects of proline metabolism on{gamma} -PGA synthesis. Our results indicated that deletion of ycgN promoted the synthesis of{gamma} -PGA by increasing the intracellular levels of {Delta}1-pyrroline-5-carboxylate to generate a transient ROS signal in B. licheniformis WX-02. This study provides the valuable information that enhanced synthesis of{gamma} -PGA by knocking out of ycgN.

microbiology↗

bioRxiv2018

Speciation with gene flow via cycles of isolation and migration: Insights from multiple mangrove taxa

Allopatric speciation requiring an unbroken period of geographical isolation has been the standard model of neo-Darwinism. While doubts have been repeatedly raised, strict allopatry without any gene flow remains a plausible mechanism in most cases. To rigorously reject strict allopatry, genomic sequences superimposed on the geological records of a well-delineated geographical barrier will be necessary. The Strait of Malacca, narrowly connecting the Pacific and Indian Ocean coasts, serves at different times either as a geographical barrier or a conduit of gene flow for coastal/marine species. We surveyed 1,700 plants from 29 populations of five common mangrove species by large scale DNA sequencing and added several whole-genome assemblies. Speciation between the two oceans is driven by cycles of isolation and gene flow due to the fluctuations in sea level leading to the opening/closing of the Strait to ocean currents. Because the time required for speciation in mangroves is longer than the isolation phases, speciation in these mangroves has proceeded through many cycles of mixing-isolation-mixing, or MIM cycles. The MIM mechanism, by relaxing the condition of no gene flow, can promote speciation in many more geographical features than strict allopatry can. Finally, the MIM mechanism of speciation is also efficient, potentially yielding mn (m>1) species after n cycles.\n\nSignificance statementMechanisms of species formation have always been a conundrum. Speciation between populations that are fully geographically isolated, or allopatric speciation, has been the standard solution in the last 50 years. Complete geographical isolation with no possibility of gene flow, however, is often untenable and is inefficient in generating the enormous biodiversity. By studying mangroves on the Indo-Malayan coasts, a global hotspot of coastal biodiversity, we were able to combine genomic data with geographical records on the Indo-Pacific barrier that separates Pacific and Indian Ocean coasts. We discovered a novel mechanism of speciation, that we call mixing-isolation-mixing (MIM) cycles. By permitting intermittent gene flow during speciation, MIM can potentially generate species at an exponential rate, thus combining speciation and biodiversity in a unified framework.

evolutionary biology↗

bioRxiv2018

An inter-chromosomal transcription hub activates the unfolded protein response in plasma cells

Previous studies have indicated that the transcription signature of antibody-secreting cells is closely associated with the induction of the unfolded protein response pathway (UPR). Here we have used genome-wide and single cell analyses to examine the folding patterns of plasma cell genomes. We found that plasma cells adopt a cartwheel configuration and undergo large-scale changes in chromatin folding at genomic regions associated with a plasma cell specific transcription signature. During plasma cell differentiation, Blimp1 assembles into an inter-chromosomal transcription hub with genes associated with the UPR, biosynthesis of the endoplasmic reticulum (ER) as well as a cluster of genes linked with Alzheimers disease. We suggest that the assembly of the Blimp1-UPR-ER transcription hub permits the coordinate activation of a wide spectrum of genes that collectively establish plasma cell identity.

immunology↗

bioRxiv2018

IL-33 regulates gene expression in intestinal epithelial cells independently of its nuclear localization

IL-33 is a cytokine found in the extracellular space (mature IL-33) or in the cell nucleus (full-length IL-33). Nuclear accumulation of IL-33 has been reported in intestinal epithelial cells (IEC) during intestinal inflammation and cancer, but a functional role for this nuclear form remains unclear. To study the role of nuclear IL-33 in IEC, we generated transgenic mice expressing full-length IL-33 in the intestinal epithelium (Vfl33 mice). Expression of full-length IL-33 in the epithelium resulted in accumulation of IL-33 protein in the nucleus and secretion of IL-33. Over-expression of full-length IL-33 by IEC did not promote gut inflammation, but induced expression of genes in the IEC and lamina propria lymphocytes (LPL) that correlated negatively with genes expressed in inflammatory bowel diseases (IBD). Because the IL-33 receptor ST2 is expressed by IEC, there was the potential that both the mature and full-length forms could mediate this effect. To specifically interrogate the transcriptional role of nuclear IL-33, we intercrossed the Vfl33 mice with ST2-deficient mice. ST2 deficiency completely abrogated the transcriptional effects elicited by IL-33 expression, suggesting that the transcriptional effects of IL-33 on IEC are mediated by its mature, not its nuclear form.\n\nHighlightsO_LIExpression of full-length IL-33 in the epithelium resulted in accumulation of IL-33 protein in the nucleus and secretion of IL-33.\nC_LIO_LIFull-length IL-33 induced differential gene expression in IEC and LPL that was negatively associated with intestinal inflammatory diseases\nC_LIO_LIIL-33 regulated gene expression in IEC via its extracellular (mature) form not via its nuclearform.\nC_LI

immunology↗

bioRxiv2018

Diet Modifies Colonic Microbiota and CD4+ T cell Repertoire to Trigger Flares in a Novel Model of Colitis Induced by IL-23

A wealth of experimental data points to immunological and environmental factors in the pathogenesis of inflammatory bowel disease (IBD). Here we study the role of IL-23, the microbiome, and the diet in the development of colitis. To promote IL-23 expression in vivo, we generated a mouse model in which IL-23 was conditionally expressed by CX3CR1+ myeloid cells, upon cyclic administration of tamoxifen in a specific diet (diet 2019). IL-23 expression induced an intestinal inflammatory disease that resembled ulcerative colitis in humans with cycles of acute disease and remission. The relapses were caused by the diet switch from the conventional diet used in our facility (diet 5053) to the diet 2019, and were not dependent on tamoxifen after the first cycle. The switch in the diet modified the microbiota, but did not alter the levels of IL-23. Colitis induction depended on the microbiota and required CD4 T lymphocytes. Colitis-inducing CD4+ T cells were found in the mesenteric lymph node and large intestine during remission and were able to trigger disease when transferred to lymphopenic mice, but only upon diet modification. The CD4 TCR repertoire in the diseased recipient Rag-/- mice had reduced diversity associated with the expansion of dominant T cell clones. These findings reveal a critical role for IL-23 in generation of a CD4+ T cell population in mice that is sensitive to a modification of intestinal bacterial flora subsequent to a dietary manipulation. Dietary changes occurring in the context of altered IL-23 expression may contribute to the onset and progression of IBD.

immunology↗

bioRxiv2017

Increased anxiety and decreased sociability in adulthood following paternal deprivation involve oxytocin in the mPFC

Early adverse experiences often have devastating consequences on adult emotional and social behavior. However, whether paternal deprivation (PD) during the pre-weaning period affects brain and behavioral development remains unexplored in socially mandarin vole (Microtus mandarinus). We found that PD increased anxiety-like behavior and attenuated social preference in adult males and females; decreased prelimbic cortex OT-immunoreactive fibers and paraventricular nucleus OT positive neurons; reduced levels of medial prefrontal cortex (mPFC) OT receptor protein in females and OT receptor and V1a receptor protein in males. Intra-prelimbic cortical OT injections reversed anxiety-like behavior and social preferences affected by PD, whereas injections of OT and OT receptor antagonist blocked this reversal. These findings demonstrate that PD leads to increased anxiety-like behavior and attenuated social preferences with involvement of the mPFC OT system. The prelimbic cortex OT system may be an important target for the treatment of disorders related to early adverse experiences.

neuroscience↗

bioRxiv2017

Identification of functional modules relevant to human neuron maturation and generation of neuron maturity index

BackgroundNeuron maturation is a critical process in neurogenesis, during which neurons gain their morphological, electrophysiological and molecular characteristics for their functions as the central components of the nervous system.\n\nResultsTo better understand the molecular changes during this process, we combined the protein-protein interaction network and public single cell RNA-seq data of mature and immature neurons to identify functional modules relevant to the neuron maturation process in humans. The analysis resulted in 33 discriminable modules which participate in varied functions including energy consumption, synaptic functions and housekeeping functions such as translation and splicing. Based on the identified modules, we trained a neuron maturity index (NMI) model for the quantification of maturation states of single neurons or purified bulk neurons. Applied to multiple single neuron transcriptome data sets of neuron development in humans and mice, the NMI model made estimation of neuron maturity states which were significantly correlated with the neuron maturation trajectories in both species, implying the reproducibility and conservation of the identified transcriptome transition.\n\nConclusionWe identified 33 functional modules whose activities were significantly correlated with single neuron maturity states, which may play important roles in the neuron maturation process.

bioinformatics↗

bioRxiv2017

Worldwide Population Structure Of Escherichia coli Reveals Two Major Subspecies

Recombination is one of the most important mechanisms of prokaryotic species evolution but its exact roles are still in debate. Here we try to infer genome-wide recombination events within a species uti-lizing a dataset of 104 complete genomes of Escherichia coli from diverse origins, among which 45 from world-wide animal-hosts are in-house sequenced using SMRT (single-molecular real time) technology.Two major clades are identified based on evidences of ecological and physiological characteristics, as well as distinct genomic features implying scarce inter-clade genetic exchange. By comparing the synteny of identical fragments genome-widely searched for each genome pair, we achieve a fine-scale map of re-combination within the population. The recombination is rather extensive within clade, which is able to break linkages between genes but does not interrupt core genome framework and primary metabolic port-folios possibly due to natural selection for physiological compatibility and ecological fitness. Meanwhile,the recombination between clades declines drastically as the phylogenetic distance increases, generally 10-fold reduced than those of the intra-clade, which establishes genetic barrier between clades. These empirical data of recombination suggest its critical role in the early stage of speciation, where recombina-tion rate differs according to phylogentic distance. The extensive intra-clade recombination coheres sister strains into a quasi-sexual group and optimizes genes or alleles to streamline physiological activities,whereas shapely declined inter-clade recombination split the population into clades adaptive to divergent ecological niches.\n\nSignificance StatementRoles of recombination in species evolution have been debated for decades due to difficulties in inferring recombination events during the early stage of speciation, especially when recombination is always complicated by frequent gene transfer events of bacterial genomes. Based on 104 high-quality complete E. coli genomes, we infer gene-centric dynamics of recombination in the formation of two E. coli clades or subpopulations, and recombination is found to be rather intensive in a within-clade fashion, which forces them to be quasi-sexual. The recombination events can be mapped among individual genomes in the context of genes and their variations; decreased between-clade and increased intra-claderecombination engender a genetic barrier that further encourages clade-specific secondary metabolic portfolios for better environmental adaptation. Recombination is thus a major force that accelerates bacterial evolution to fit ecological diversity.

microbiology↗