Biology subjects

Jung, S.

Publications and source records attributed to Jung, S..

6 recordsLinked to original sources

bioRxiv2018

Microglial SIRPα regulates the emergence of CD11c+ microglia and demyelination damage in white matter

A characteristic subset of microglia expressing CD11c appears in response to brain damage. However, the functional role of CD11c+ microglia, as well as the mechanism of its induction, are poorly understood. Here we report that the genetic ablation of signal regulatory protein (SIRP), a membrane protein, induced CD11c+ microglia in the brain white matter. Mice lacking CD47, a physiological ligand of SIRP, and microglia-specific SIRP knockout mice exhibited the same phenotype, suggesting the interaction between microglial SIRP and CD47 on neighbouring cells suppressed the emergence of CD11c+ microglia. A lack of SIRP did not cause detectable damage in the white matter, but resulted in the increased expression of genes characteristic of the repair phase after demyelination. In addition, cuprizone-induced demyelination was alleviated by the microglia-specific ablation of SIRP. Thus, microglial SIRP suppresses the induction of CD11c+ microglia that have the potential to accelerate the repair of damaged white matter.

neuroscience↗

bioRxiv2018

Temporally varying isotopic niche overlap of the invasive ctenophore Mnemiopsis leidyi with other zooplanktivores in the western Dutch Wadden Sea

The invasive ctenophore Mnemiopsis leidyi can be a major predator of zooplankton in areas where it has been introduced. In this study, the possible competition of M. leidyi with native macroplankton and nekton in the western Dutch Wadden Sea was investigated in March-August, 2011 by determining and comparing isotopic niches of zooplanktivores. Stable carbon and nitrogen isotope signatures were determined from tissue samples of fish, scyphozoa, hydromedusa, ctenophores, crustaceans and cephalopods.{delta} 15N of M. leidyi was positively related to ctenophore size, suggesting that small ctenophores occupied a lower trophic level than large ones. A cluster analysis showed that in the spring and early summer period, when M. leidyi densities are low, average{delta} 13C and{delta} 15N ratios of the invasive M. leidyi were similar to those of most other gelatinous zooplankton and pelagic fish species sampled. At the beginning of the bloom period in August there was no overlap in isotopic niche of M. leidyi with that of any other pelagic zooplanktivore. During this month the population consisted mainly of larvae and juveniles with lower{delta} 15N ratios. At present, M. leidyi appears not to be a significant competitor for other gelatinous zooplankton and fish species because the period of high diet overlap with other consumers was also the period in which M. leidyi was least abundant.

ecology↗

bioRxiv2018

Updating genome annotation for the microbial cell factory Aspergillus niger using gene co-expression networks

A significant challenge in our understanding of biological systems is the high number of genes with unknown function in many genomes. The fungal genus Aspergillus contains important pathogens of humans, model organisms, and microbial cell factories. Aspergillus niger is used to produce organic acids, proteins, and is a promising source of new bioactive secondary metabolites. Out of the 14,165 open reading frames predicted in the A. niger genome of only 2% have been experimentally verified and over 6,000 are hypothetical. Here we show that gene co-expression network analysis can be used to overcome this limitation. A meta-analysis of 155 transcriptomics experiments generated co-expression networks for 9,579 genes ([~]65%) of the A. niger genome. By populating this dataset with over 1,200 gene functional experiments from the genus Aspergillus and performing gene ontology enrichment, we could infer biological processes for 9,263 of A. niger genes, including 2,970 hypothetical genes. Experimental validation of selected co-expression sub-networks uncovered four transcription factors involved in secondary metabolite synthesis, which were used to activate production of multiple natural products. This study constitutes a significant step towards systems-level understanding of A. niger, and the datasets can be used to fuel discoveries of model systems, fungal pathogens, and biotechnology.

systems biology↗

bioRxiv2018

Engrafted parenchymal brain macrophages differ from host microglia in transcriptome, epigenome and responsiveness to challenge

Microglia are yolk sac-derived macrophages residing in the parenchyma of brain and spinal cord, where they interact with neurons and other glial cells by constantly probing their surroundings with dynamic extensions. Following different conditioning paradigms and bone marrow (BM) / hematopoietic stem cell (HSC) transplantation, graft-derived cells seed the brain and persistently contribute to the parenchymal brain macrophage compartment. Here we establish that these cells acquire over time microglia characteristics, including ramified morphology, longevity, radio-resistance and clonal expansion. However, even following prolonged CNS residence, transcriptomes and epigenomes of engrafted HSC-derived macrophages remain distinct from yolk sac-derived host microglia. Furthermore, BM graft-derived cells display discrete responses to peripheral endotoxin challenge, as compared to host microglia. Also in human HSC transplant recipients, engrafted cells remain distinct from host microglia, extending our finding to clinical settings. Collectively, our data emphasize the molecular and functional heterogeneity of parenchymal brain macrophages and highlight potential clinical implications for patients treated by HSC gene therapy.

immunology↗

bioRxiv2018

Microtubule minus-end aster organization is driven by processive HSET-tubulin clusters

Higher-order structures of the microtubule (MT) cytoskeleton are comprised of two architectures: bundles and asters. Although both architectures are critical for cellular function, the molecular pathways that drive aster formation are poorly understood. Here, we study aster formation by human minus-end directed kinesin-14 (HSET/KIFC1). We show that HSET is incapable of forming asters from pre-formed, non-growing MTs, but rapidly forms MT asters in the presence of soluble tubulin. HSET binds soluble (non-polymer) tubulin via its N-terminal tail domain to form heterogeneous HSET-tubulin \"clusters\" containing multiple motors. Cluster formation induces motor processivity and rescues the formation of asters from non-growing MTs. We then show that excess soluble tubulin stimulates aster formation in HeLa cells overexpressing HSET during mitosis. We propose a model where HSET can toggle between MT bundle and aster formation in a manner governed by the availability of soluble tubulin.

biophysics↗

bioRxiv2018

Atlas of Transcription Factor Binding Sites from ENCODE DNase Hypersensitivity Data Across 27 Tissue Types

There is intense interest in mapping the tissue-specific binding sites of transcription factors in the human genome to reconstruct gene regulatory networks and predict functions for non-coding genetic variation. DNase-seq footprinting provides a means to predict genome-wide binding sites for hundreds of transcription factors (TFs) simultaneously. However, despite the public availability of DNase-seq data for hundreds of samples, there is neither a unified analytical workflow nor a publicly accessible database providing the locations of footprints across all available samples. Here, we implemented a workflow for uniform processing of footprints using two state-of-the-art footprinting algorithms: Wellington and HINT. Our workflow scans the footprints generated by these algorithms for 1,530 sequence motifs to predict binding sites for 1,515 human transcription factors. We applied our workflow to detect footprints in 192 DNase-seq experiments from ENCODE spanning 27 human tissues. This collection of footprints describes an expansive landscape of potential TF occupancy. At thresholds optimized through machine learning, we report high-quality footprints covering 9.8% of the human genome. These footprints were enriched for true positive TF binding sites as defined by ChIP-seq peaks, as well as for genetic variants associated with changes in gene expression. Integrating our footprint atlas with summary statistics from genome-wide association studies revealed that risk for neuropsychiatric traits was enriched specifically at highly-scoring footprints in human brain, while risk for immune traits was enriched specifically at highly-scoring footprints in human lymphoblasts. Our cloud-based workflow is available at github.com/globusgenomics/genomics-footprint and a database with all footprints and TF binding site predictions are publicly available at http://data.nemoarchive.org/other/grant/sament/sament/footprint_atlas.

bioinformatics↗