Biology subjects

Yin, J.

Publications and source records attributed to Yin, J..

151 records · Page 9Linked to original sources

bioRxiv2018

Comprehensive analysis of immune evasion in breast cancer by single-cell RNA-seq

The tumor microenvironment is composed of numerous cell types, including tumor, immune and stromal cells. Cancer cells interact with the tumor microenvironment to suppress anticancer immunity. In this study, we molecularly dissected the tumor microenvironment of breast cancer by single-cell RNA-seq. We profiled the breast cancer tumor microenvironment by analyzing the single-cell transcriptomes of 52,163 cells from the tumor tissues of 15 breast cancer patients. The tumor cells and immune cells from individual patients were analyzed simultaneously at the single-cell level. This study explores the diversity of the cell types in the tumor microenvironment and provides information on the mechanisms of escape from clearance by immune cells in breast cancer.\n\nOne Sentence SummaryLandscape of tumor cells and immune cells in breast cancer by single cell RNA-seq

cancer biology↗

bioRxiv2018

A direct comparison of four high risk human papilloma virus tests versus the cobas test for detecting cervical intraepithelial neoplasia and cervical cancer

This study is to evaluate performances and genotyping capabilities of four human papilloma virus (HR-HPV) tests based on real-time polymerase chain reaction (PCR) technology platforms compared with the cobas test. Discordant results were further analyzed using INNO-LiPA HPV genotyping test, the gold standard laboratory test to determine presence and type of HPV infection. Over 200 samples from Hospital patients were collected and analyzed using five HR-HPV tests. Women with positive test results were referred directly to colposcopy. If a positive result was returned, biopsies were administered for pathological classification. Clinical performances and genotyping capabilities between the four HR-HPV and cobas tests were compared and contrasted. High levels of agreement were observed, though all HR-HPV tests presented discrepancies compared with the cobas test. Cervical intraepithelial neoplasia Grade 2 or higher lesions (CIN2+) was set as the threshold, and all five tests performed with equally high sensitivity. Lower levels of specificity were observed across all five tests. Results suggest the four HR-HPV tests analyzed are as effective as the cobas test in genotyping capacities and diagnosing CIN. Therefore, these test kits should be used for HPV screening, especially in developing nations because they are cost effective and reliable. Minor discrepancies between tests are generally unavoidable though this may add complexity to the clinical decision-making process. As such, we recommend that efforts be made to standardize HPV genotyping tests as well as to optimize clinical sensitivity and specificity. Focusing on these issues will drive the development of HPV detection techniques, therefore save lives.

epidemiology↗

bioRxiv2018

The MarR Family Regulator BmrR is involved in Bile Tolerance of Bifidobacterium longum BBMN68 via Controlling the Expression of an ABC-Transporter

In order to colonize the human gastrointestinal tract and exert their beneficial effects, bifidobacteria must effectively cope with the toxic bile salts in the intestine, but the molecular mechanism underlying bile tolerance is poorly understood. In this study, heterologous expression of a MarR family transcriptional regulator BmrR significantly reduced ox-bile resistance of Lactococcus lactis NZ9000, suggesting that it might play a role in bile stress response. In silico analysis combined with RT-PCR assay demonstrated that bmrR was co-transcribed with bmrA and bmrB, which encoded multidrug resistance (MDR) ABC transporters. Promoter prediction and EMSA assay revealed that BmrR could autoregulate the bmrRAB operon by binding to bmr box (ATTGTTG-6nt-CAACAAT) in the promoter region. Moreover, heterologous expression of bmrA and bmrB in L. lactis showed 20.77-fold higher tolerance to 0.10% ox-bile compared to wild type strain. In addition, ox-bile could disrupt the DNA binding activity of BmrR as a ligand. Taken together, our findings indicate that bmrRAB operon is autoregulated by transcriptional regulator BmrR and ox-bile serves as an inducer to activate the bile efflux transporter BmrAB in response to bile stress in B. longum BBMN68.\n\nImportanceBifidobacteria are natural inhabitants of the human intestinal tract. Some bifidobacterial strains are used as probiotics in fermented dairy production because of their health-promoting effects. Following consumption, bifidobacteria finally colonize the lower intestinal tract where the concentration of bile salts remains nearly 0.05% to 2.0%. Bile salts as detergent-like antimicrobial compounds can cause disruption of the cellular membrane, protein misfolding and DNA damage. Therefore, tolerance to physiological bile stress is indeed essential for bifidobacteria to survive and exert the probiotic effects in gastrointestinal tract. In B. longum BBMN68, the MarR-type regulator BmrR was involved in bile stress response by auto-regulating bmrRAB operon and ox-bile as an inducer could increase the expression of BmrAB transporter to enhance the bile tolerance of BBMN68.This is the first report about functional analysis of bmrRAB operon in bile stress response, which will provide new insight into bile tolerance mechanisms in Bifidobacterium and other bacteria.

microbiology↗

bioRxiv2018

Phylogenetically novel uncultured microbial cells dominate Earth microbiomes

To unequivocally determine a microbes physiology, including its metabolism, environmental roles, and growth characteristics, it must be grown in a laboratory culture. Unfortunately, many phylogenetically-novel groups have never been cultured, so their physiologies have only been inferred from genomics and environmental characteristics. Although the diversity, or number of different taxonomic groups, of uncultured clades has been well-studied, their global abundances, or number of cells in any given environment, have not been assessed. We quantified the degree of similarity of 16S rRNA gene sequences from diverse environments in publicly-available metagenome and metatranscriptome databases, which we show are largely free of the culture-bias present in primer-amplified 16S rRNA gene surveys, to their nearest cultured relatives. Whether normalized to scaffold read depths or not, the highest abundance of metagenomic 16S rRNA gene sequences belong to phylogenetically novel uncultured groups in seawater, freshwater, terrestrial subsurface, soil, hypersaline environments, marine sediment, hot springs, hydrothermal vents, non-human hosts, snow and bioreactors (22-87% uncultured genera to classes and 0-64% uncultured phyla). The exceptions were human and human-associated environments which were dominated by cultured genera (45-97%). We estimate that uncultured genera and phyla could comprise 7.3 x 1029 (81%) and 2.2 x 1029 (25%) microbial cells, respectively. Uncultured phyla were over-represented in meta transcript omes relative to metagenomes (46-84% of sequences in a given environment), suggesting that they are viable, and possibly more active than cultured clades. Therefore, uncultured microbes, often from deeply phylogenetically divergent groups, dominate non-human environments on Earth, and their undiscovered physiologies may matter for Earth systems.

microbiology↗

bioRxiv2018

Functional repair after ischemic injury through high efficiency in situ astrocyte-to-neuron conversion

Mammalian brains have largely lost internal neural regeneration capability except for a few discrete neurogenic niches. After brain injury, the cerebral cortex is especially difficult to repair due to its extremely low rate of adult neurogenesis. Previous studies have converted glial cells into neurons, but the total number of neurons generated is rather limited, casting doubt about its therapeutic potential. Here, we demonstrate that high-efficiency neuroregeneration can be achieved in adult mammalian brains by making use of an engineered AAV Cre-FLEX system to convert a large number of reactive astrocytes into functional neurons. Specifically, using a combination of GFAP::Cre and FLEX-NeuroD1 AAV system, we were able to regenerate enough new neurons from astrocytes to cover about 40% of the neurons lost from an ischemic injury (400 NeuN+ new neurons/mm2), compared to previously reported an average of <1% of cortical neurons (2-8 NeuN+ neurons/mm2) in an ischemic-injured adult mammalian cortex. Importantly, this in situ astrocyte-to-neuron conversion process also improved survival of injured pre-existing neurons, (additional 400 neurons/mm2), leading to a repaired motor cortex with layered cortical structures. Moreover, NeuroD1-converted neurons not only form functional neural circuits but also rescue motor and memory deficits after ischemic injury. Our results establish the proof-of-principle that a highly efficient in situ astrocyte-to-neuron conversion approach provides a novel treatment for neurological disorders that are in need of new neurons.

neuroscience↗

bioRxiv2017

Low-level mitochondrial heteroplasmy modulates DNA replication, glucose metabolism and lifespan in mice

Mutations in mitochondrial DNA (mtDNA) lead to heteroplasmy, i.e. the intracellular coexistence of wild-type and mutant mtDNA strands, which impact a wide spectrum of diseases but also physiological processes, including endurance exercise performance in athletes. However, the phenotypic consequences of limited levels of naturally-arising heteroplasmy have not been experimentally studied to date. We hence generated a conplastic mouse strain carrying the mitochondrial genome of a AKR/J mouse strain (B6-mtAKR) together with a C57BL/6J nuclear genomic background, leading to >20% heteroplasmy in the origin of light-strand DNA replication (OriL). These conplastic mice demonstrate a shorter lifespan as well as dysregulation of multiple metabolic pathways, culminating in impaired glucose metabolism, compared to wild-type C57BL/6J mice carrying lower levels of heteroplasmy. Our results indicate that physiologically relevant differences in mtDNA heteroplasmy levels at a single, functionally important site impair metabolic health and lifespan in mice.\n\nHighlightsO_LIWe identify heteroplasmy of the adenine-repeat variation (9 to 13A) in nt5172 in the origin of light-strand DNA replication (OriL) in inbred mice.\nC_LIO_LIB6-mtAKR mice carry >20% 12A heteroplasmy in the OriL, while B6 mice carry only [~] 10% heteroplasmy.\nC_LIO_LIThe level of 12A heteroplasmy correlates to mtDNA copy number, glucose metabolism, and lifespan in mice.\nC_LIO_LIGiven the established role of mtDNA heteroplasmy in regards to endurance exercise performance in athletes, these findings may impact our understanding of metabolism and aging in humans.\nC_LI

genetics↗

bioRxiv2017

Dark period transcriptomic and metabolic profiling of two diverse Eutrema salsugineum accessions

Eutrema salsugineum is a model species for the study of plant adaptation to abiotic stresses. Two accessions of E. salsugineum, Shandong (SH) and Yukon (YK), exhibit contrasting morphology, biotic, and abiotic stress tolerance. Transcriptome and metabolic profiling from tissue samples collected during the dark period were used to investigate the molecular and metabolic bases of these contrasting phenotypes. RNA sequencing identified 17,888 expressed genes, of which 157 were not in the published reference genome and 65 were detected for the first time. Differential expression was detected for only 31 genes. The RNA sequencing data contained 14,808 single nucleotide polymorphisms (SNPs) in transcripts, 3,925 of which are newly identified. Among the differentially expressed genes, there were no obvious candidates for the physiological or morphological differences between SH and YK. Metabolic profiling indicated that YK accumulates free fatty acids and long-chain fatty acid derivatives as compared to SH; whereas sugars are more abundant in SH. Metabolite levels suggest that carbohydrate and respiratory metabolism, including starch degradation, is more active during the first half of the dark period in SH. These metabolic differences may explain the greater biomass accumulation in YK over SH. The accumulation of 56% of the identified metabolites was lower in F1 hybrids than the mid-parent averages and the accumulation of 17% of the metabolites in F1 plants transgressed the level in both parents. Concentrations of several metabolites in F1 hybrids agree with previous studies and suggest a role for primary metabolism in heterosis. The improved annotation of the E. salsugineum genome and newly-identified high-quality SNPs will permit accelerated studies using the standing variation in this species to elucidate the mechanisms of its diverse adaptations to the environment.

plant biology↗