Biology subjects

Yuan, J.

Publications and source records attributed to Yuan, J..

At least 163 records · Page 9Linked to original sources

bioRxiv2019

Complete single neuron reconstruction reveals morphological diversity in molecularly defined claustral and cortical neuron types

Ever since the seminal findings of Ramon y Cajal, dendritic and axonal morphology has been recognized as a defining feature of neuronal types. Yet our knowledge concerning the diversity of neuronal morphologies, in particular distal axonal projection patterns, is extremely limited. To systematically obtain single neuron full morphology on a brain-wide scale, we established a platform with five major components: sparse labeling, whole-brain imaging, reconstruction, registration, and classification. We achieved sparse, robust and consistent fluorescent labeling of a wide range of neuronal types by combining transgenic or viral Cre delivery with novel transgenic reporter lines. We acquired high-resolution whole-brain fluorescent images from a large set of sparsely labeled brains using fluorescence micro-optical sectioning tomography (fMOST). We developed a set of software tools for efficient large-volume image data processing, registration to the Allen Mouse Brain Common Coordinate Framework (CCF), and computer-assisted morphological reconstruction. We reconstructed and analyzed the complete morphologies of 1,708 neurons from the striatum, thalamus, cortex and claustrum. Finally, we classified these cells into multiple morphological and projection types and identified a set of region-specific organizational rules of long-range axonal projections at the single cell level. Specifically, different neuron types from different regions follow highly distinct rules in convergent or divergent projection, feedforward or feedback axon termination patterns, and between-cell homogeneity or heterogeneity. Major molecularly defined classes or types of neurons have correspondingly distinct morphological and projection patterns, however, we also identify further remarkably extensive morphological and projection diversity at more fine-grained levels within the major types that cannot presently be accounted for by preexisting transcriptomic subtypes. These insights reinforce the importance of full morphological characterization of brain cell types and suggest a plethora of ways different cell types and individual neurons may contribute to the function of their respective circuits.

neuroscience↗

bioRxiv2019

Alteration of Gut Microbiome in Lung Cancer Patients

Lung cancer is the leading cause of cancer death. Better understanding of factors and pathways involved in lung cancer is needed to improve diagnose and treatment strategies. Recent studies have provided insights into the possible correlation between intestinal dysbiosis and cancer development. Although the immunological relationship between gut and lung had been suggested by many researches, however, to date, no study had investigated the characterization of gut microbiome in treatment naive lung cancer patients, whether it is distinct from that of health individuals and contribute to the onset and development of lung cancer remain unclear. In this study, we investigated whether gut microbiome of lung cancer patients (LC, n=28) is altered compare with that of matched healthy individuals (HC, n=19) by high throughout sequencing of the V3-V4 regions of 16S rDNA in their fecal samples. We also identified microbiota signatures specific for different histological types of lung cancer, including SSC, ADC, and SCLC. The gut microbiome of lung cancer patients is characterized by decreased relative abundance of Prevotella, and increased bacteria groups such as Actinomyces, and Streptococcus, etc. We also detected a mild structural shift in gut microbiome between ADC and SCLC patients. Our results showed that the gut microbiome of lung cancer patients altered significantly compared with healthy individuals. However, the association between microbial dysbiosis and lung cancer is not clearly understood, future studies involving larger cohorts and metagenomics, or metabolomics, may elucidate the correlations between gut microbiota and lung cancer development.\n\nIMPORTANCEThis is the first report to show the alteration of gut microbiome in lung cancer patients. Our results showed that the gut microbiome of lung cancer patients altered significantly compared with healthy individuals.

microbiology↗

bioRxiv2019

metaFlye: scalable long-read metagenome assembly using repeat graphs

Long-read sequencing technologies substantially improved assemblies of many isolate bacterial genomes as compared to fragmented assemblies produced with short-read technologies. However, assembling complex metagenomic datasets remains a challenge even for the state-of-the-art long-read assemblers. To address this gap, we present the metaFlye assembler and demonstrate that it generates highly contiguous and accurate metagenome assemblies. In contrast to short-read metagenomics assemblers that typically fail to reconstruct full-length 16S RNA genes, metaFlye captures many 16S RNA genes within long contigs, thus providing new opportunities for analyzing the microbial \"dark matter of life\". We also demonstrate that long-read metagenome assemblers significantly improve full-length plasmid and virus reconstruction as compared to short-read assemblers and reveal many novel plasmids and viruses.

bioinformatics↗

bioRxiv2019

Redistribution of NORTIA in response to pollen tube arrival facilitates fertilization in Arabidopsis thaliana

During gamete delivery in Arabidopsis thaliana, intercellular communication between the attracted pollen tube and the receptive synergid cell leads to subcellular events in both cells culminating in the rupture of the tip-growing pollen tube and release of the sperm cells to achieve double fertilization. Live imaging of pollen tube reception revealed dynamic subcellular changes that occur in the female synergid cells. Pollen tube arrival triggers the trafficking of NORTIA (NTA) MLO protein from Golgi-associated compartments and the accumulation of endosomes at or near the synergid filiform apparatus, a membrane-rich region that acts as the site of communication between the pollen tube and synergids. Domain swaps and site-directed mutagenesis reveal that NTAs C-terminal cytoplasmic tail with its calmodulin-binding domain influences the subcellular localization and function of NTA in pollen tube reception and that accumulation of NTA at the filiform apparatus is necessary and sufficient for MLO function in pollen tube reception.

plant biology↗

bioRxiv2019

A single-cell reference map for human blood and tissue T cell activation reveals functional states in health and disease

Human T cells coordinate adaptive immunity by localization in diverse tissue sites, though blood T cells are the most readily studied. Here, we used single-cell RNA-seq to define the functional responses of T cells isolated from human lungs, lymph nodes, bone marrow, and blood to TCR-stimulation. We reveal how human T cells in tissues relate to those in blood, and define activation states for CD4+ and CD8+T cells across all sites, including an interferon-response state for CD4+T cells and distinct effector states for CD8+T cells. We further show how profiles of individual tumor-associated T cells can be projected onto this healthy reference map, revealing their functional state.

immunology↗

bioRxiv2019

HMGB1 orchestrates uterine macrophage trafficking to safeguard embryo implantation

A reciprocal communication between the implantation-competent blastocyst and the receptive uterus is essential to implantation. Blastocyst implantation is considered to be a regulated proinflammatory response in the uterus, however the underlining mechanism remains elusive. Here, we provide genetic evidence that High-mobility group protein Box-1 (HMGB1), expressed in uterine cell nuclei, restricts inflammatory responses during the periimplantation period. Conditional deletion of uterine Hmgb1 by using a Pgr-Cre driver (Pgrcre/+Hmgb1f/f) shows substantial infertility because of defective implantation and subsequent adverse ripple effects. These mice accumulate and retain an increased number of macrophages in the stroma on day 4 of pregnancy with a unique enrichment of macrophages in the stroma encircling the blastocyst on day 5, evoking inflammatory responses. These results are in contrast to previous findings that HMBG1 is an internal alarmin. In search for the mechanism, we found that Hmgb1-deleted stromal cells show reduced activation of PR and decreased Hoxa10 expression, providing evidence that PR and Hoxa10 mediated regression of inflammation is mediated by HMGB1. In addition, levels of two macrophage attractants CSF1 and CCL2 are elevated in the stroma and in vitro studies show that CSF1 specifically attracts macrophages which is abrogated if challenged with a CSF1 receptor antagonist. The results suggest that Hmgb1 contributes to successful blastocyst implantation by regulating macrophage trafficking in the stroma to prevent excessive inflammatory responses.

developmental biology↗

bioRxiv2018

HiAlc Klebsiella pneumonia, one of potential chief culprits of non-alcoholic fatty liver disease: through generation of endogenous ethanol

Non-alcoholic fatty liver disease (NAFLD), a prelude of cirrhosis and hepatocellular carcinoma, is the most common chronic liver disease worldwide. NAFLD has been considerated to be associated with the composition of gut microbiota. However, causal relationship between change of gut microbiome and NAFLD remains unclear. Here we show that Klebsiella pneumoniae was significantly associated with NAFLD through inducing generation of endogenous ethanol. A strain of high alcohol-producing Klebsiella pneumoniae (HiAlc Kpn) was initially isolated from fecal samples of patient with non-alcoholic steatohepatitis (NASH) accompanied with auto-brewery syndrome (ABS). Gavage of HiAlc Kpn was capable of inducing murine model of fatty liver disease (FLD) in which had typical pathological changes of hepatic steatosis and similar liver gene expression profiles to those of alcohol intake in mice. Data derived from germ-free mice by gnotobiotic gavage further demonstrated that the HiAlc Kpn is the major cause of the changes in FLD mice. Furthermore, using proteomic and metabolitic analysis, we found that HiAlc Kpn induced generation of endogenous alcohol through the 2,3-butanediol fermentation pathway. More interestingly, the blood alcohol concentration was elevated in FLD mice induced by HiAlc Kpn after glucose intake. Clinical analysis showed that HiAlc Kpn were observed in up to 60% of patients with NAFLD. Our results suggested that HiAlc Kpn make important contribution to NAFLD, possibly through generation of the endogenous alcohol. Thus, targeting these bacteria might provide a novel therapeutic for clinical treatment of NAFLD.\n\nIn BriefFatty liver disease induced by high alcohol-producing Klebsiella pneumoniae\n\nCompeting Financial Interest StatementThe authors declare no conflicts of interest.

microbiology↗

bioRxiv2018

HSCs contribute actively to native multilineage hematopoiesis but with reduced differentiation capacity upon aging

A hallmark of adult hematopoiesis is the continuous replacement of blood cells with limited lifespans. It is well established that adult hematopoietic stem cells (HSCs) are active contributors to these processes after transplantation, yet their role in native hematopoiesis has recently been called into question. Here, we use inducible lineage tracing from genetically marked adult HSCs to explore their roles in the steady state. We show that adult HSCs contribute robustly to all lineages via intermediate progenitor cells, but with neglible production of hematopoietic cells with a known fetal origin. We further reveal that the timing for regeneration of distinct blood lineages varies substantially. Finally, HSC contribution to multilineage hematopoiesis in aged animals declines with increasing age. Therefore, while HSCs are active contributors to native adult hematopoiesis, it appears that the numerical increase of HSCs is a physiologically relevant compensatory mechanism to account for a reduced differentiation capacity with age.

developmental biology↗

bioRxiv2018

COMPASS Family Histone Methyltransferase ASH2L Mediates Corticogenesis via Transcriptional Regulation of Wnt Signalling

Cell fate specification in neural progenitor cells (NPCs) is orchestrated via extrinsic and intrinsic molecular programs, and histone methylation in these decisions has been ascribed to a crucial function regulating gene expression. Here, we show that the COMPASS family histone methyltransferase co-factor ASH2L is required in NPCs proliferation and upper layer cortical projection neurons production and position. Deletion of Ash2l impairs trimethylation of H3K4 and transcriptional machinery specifically for subsets of Wnt-{beta}-catenin signalling, disrupting their transcription and consequently inhibiting the proliferation ability of NPCs in late stages of neurogenesis. Consistently, Ash2l conditional mutants exhibit thinning neocortex with reduced upper layer neurons and altered neuronal position. Moreover, overexpressing {beta}-catenin after Ash2l elimination or knockdown can rescue the proliferation deficiency of NPCs both in vivo and in vitro. These results demonstrate an essential and highly specific role for Ash2l in controlling NPCs proliferation and late-born neurons lamination in corticogenesis via transcriptionally regulating Wnt-{beta}-catenin signalling, and provide clues to how the COMPASS family epigenetic factors coordinate cell fate determination during cortex development.

neuroscience↗

bioRxiv2018

Mate-pair Library Construction with Controlled Polymerization Enables Comprehensive Structural Rearrangement Detection

The diversity of disease presentations warrants one single assay for detection and delineation of various genomic disorders. Herein, we describe a gel-free and biotin-capture-free mate-pair method through coupling Controlled Polymerizations by Adapter-Ligation (CP-AL). We first demonstrated the feasibility and ease-of-use in monitoring DNA nick-translation and primer extension by limiting the nucleotide input. By coupling these two controlled polymerizations by a reported non-conventional adapter ligation reaction 3 branch ligation, we evidenced that CP-AL significantly increased DNA-circularization efficiency (by 4-fold) and was applicable for different sequencing methods but at a faction of current cost. Its advantages were further demonstrated by fully elimination of small-insert-contaminated (by 39.3-fold) with a ~50% increment of physical coverage, and producing uniform genome/exome coverage and the lowest chimeric rate. It achieved single-nucleotide variants detection with sensitivity and specificity up to 97.3 and 99.7%, respectively, compared with data from small-insert libraries. In addition, this method can provide a comprehensive delineation of structural rearrangements, evidenced by a potential diagnosis in a patient with oligo-atheno-terato-spermia. Moreover, it enables accurate mutation identification by integration of genomic variants from different aberration types. Overall, it provides a potential single-integrated solution for detecting various genomic variants, facilitating a genetic diagnosis in human diseases.

genomics↗

bioRxiv2018

Altered Bacteria-Fungi Inter-Kingdom Network in Gut of Ankylosing Spondylitis Patients

Intestinal bacterial dysbiosis has been increasingly linked to Ankylosing Spondylitis (AS), which is a prototypic and best studied subtype of Spondyloarthritis (SpA). Fungi and bacteria coexist in human gut and interact with each other, although they have been shown to contribute actively to health or diseases, no studies have investigated whether fungal microbiota in AS patients is perturbed. In this study, fecal samples of 22 AS patients, with clinical and radiographic assessments, and 16 healthy controls (HCs) were collected to systematically characterize the gut microbiota and mycobiota in AS patients by 16S rDNA and ITS2-based DNA sequencing. The relationships between therapeutic regimens, disease activity, radiographic damage of AS and gut micro/mycobiome were investigated. Our results showed a distinct mycobiota pattern in AS in addition to microbiota dysbiosis. The gut mycobiome of AS patients was characterized by higher taxonomic levels of Ascomycota, especially the class of Dothideomycetes, and decreased abundance of Basidiomycota, which was mainly contributed by the decease of Agaricales. Compared to HCs, changing of the ITS2/16S biodiversity ratio, and bacteria-fungi interkingdom network were observed in AS patients. Alteration of gut mycobiota was associated with different therapeutic regimens, disease activity, as well as different degrees of radiographic damage. Moreover, we unraveled a disease-specific interkingdom network alteration in AS. Finally, we also identified some trends suggesting that different therapeutic regimens may induce changing of both bacterial and fungal microbiota in AS.\n\nIMPORTANCEHuman gut is colonized by diverse fungi (mycobiome), and they have long been suspected in the pathogenesis of Spondyloarthritis (SpA). Our study unraveled a disease-specific interkingdom network alteration in AS, suggesting that fungi, or the interkingdom interactions between bacteria and fungi, may play an essential role in AS development. However, limited by sample size and indeep mechanism studies, further large scale investigations on the characterization of gut mycobiome in AS patients are needed to form a foundation for research into the relationship between mycobiota dysbiosis and AS development.

microbiology↗

bioRxiv2018

Mycobacteria-specific CD4+IFN-γ+ cell expresses naïve-surface markers and confers superior protection against tuberculosis infection compared to central and effector memory CD4+ T cell subsets

Failure of the most recent tuberculosis (TB) vaccine trial to boost BCG mediated anti-TB immunity despite highly durable Th1-specific central (TCM) and effector (TEM) memory cell responses, highlights the importance of identifying optimal T cell targets for protective vaccines. Here we describe a novel, Mycobacterium tuberculosis (Mtb)-specific IFN-{gamma}+CD4+ T cell population expressing surface markers characteristic of naive T cells (TNLM), that were induced in both human (CD45RA+CCR7+CD27+CD95-) and murine (CD62L+CD44-Sca-1+CD122-) systems in response to mycobacteria. In BCG vaccinated subjects and those with latent TB infection, TNLM cells, compared to bonafide naive CD4+ T cells were identified by absence of CD95 expression and had increased expression CCR7 and CD27, the activation markers T-bet, CD69 and PD-1 and the survival marker CD74. Increased TNLM frequencies were noted in the lung and spleen of wild type C57BL6 mice at 2 weeks after infection with Mtb, and progressively decreased at later time points, a pattern not seen in TNF-+CD4+ T cells expressing naive cell surface markers. Importantly, adoptive transfer of highly purified TNLM from vaccinated ESAT-61-20-specific TCR transgenic mice conferred superior protection against Mtb infection in Rag-/- mice when compared with total meory populations (central and effector memory cells). Thus, TNLM cells may represent a memory T cell population that if optimally targeted may significantly improve future TB vaccine responses.

immunology↗

bioRxiv2018

De novo Gene Signature Identification from Single-Cell RNA-Seq with Hierarchical Poisson Factorization

Common approaches to gene signature discovery in single cell RNA-sequencing (scRNA-seq) depend upon predefined structures like clusters or pseudo-temporal order, require prior normalization, or do not account for the sparsity of single cell data. We present single cell Hierarchical Poisson Factorization (scHPF), a Bayesian factorization method that adapts Hierarchical Poisson Factorization [1] for de novo discovery of both continuous and discrete expression patterns from scRNA-seq. scHPF does not require prior normalization and captures statistical properties of single cell data better than other methods in benchmark datasets. Applied to scRNA-seq of the core and margin of a high-grade glioma, scHPF uncovers marked differences in the abundance of glioma subpopulations across tumor regions and subtle, regionally-associated expression biases within glioma subpopulations. scHFP revealed an expression signature that was spatially biased towards the glioma-infiltrated margins and associated with inferior survival in glioblastoma.

systems biology↗

bioRxiv2018

Impact of Premorbid Infection on Onset and Disease Activity of Rheumatoid Arthritis

ObjectiveInfections have been implicated in rheumatoid arthritis (RA) development. However, the impact of premorbid infection on initiation and perpetuation of RA has not been well elucidated. Thus, we sought to conduct a large scale on-site survey to study whether premorbid infection may trigger RA and influence status of the disease.\n\nMethodsPremorbid infectious events were collected in cohort of 902 RA patients from December 2015 to June 2016. Type of infections prior to RA onset and its possible effects on disease status were analyzed.\n\nResultThree hundred and thirty-four out of 902 patients (37.03%) experienced infections within one month preceding RA onset. The most frequent infections were respiratory (16.08%), intestinal (11.09%) and urinary tract (9.87%) infection, respectively. The infection was associated with increased disease activity. Early onset was found in patients with urinary infection. High disease activity risk was increased in patients who pre-exposure to urinary infection (OR=3.813, 95%CI=1.717-12.418) and upper respiratory infection (OR=2.475, 95%CI= 0.971-6.312).\n\nConclusionPre-exposure infections are associated with development of RA. Severe disease status of RA and persistent of active disease status are related to preceding infections.

epidemiology↗

bioRxiv2018

A Genome-Wide Association Study Reveals a Novel Regulator of Ovule Number and Fertility in Arabidopsis thaliana

Ovules contain the female gametophytes which are fertilized during pollination to initiate seed development. Thus, the number of ovules that are produced during flower development is an important determinant of seed crop yield and plant fitness. Mutants with pleiotropic effects on development often alter the number of ovules, but specific regulators of ovule number have been difficult to identify in traditional mutant screens. We used natural variation in Arabidopsis accessions to identify new genes involved in the regulation of ovule number. The ovule numbers per flower of 189 Arabidopsis accessions were determined and found to have broad phenotypic variation that ranged from 39 ovules to 84 ovules per pistil. Genome-Wide Association tests revealed several genomic regions that are associated with ovule number. T-DNA insertion lines in candidate genes from the most significantly associated loci were screened for ovule number phenotypes. The NEW ENHANCER of ROOT DWARFISM (NERD1) gene was found to have pleiotropic effects on plant fertility that include regulation of ovule number and both male and female gametophyte development. Overexpression of NERD1 increased ovule number per fruit in a background-dependent manner and more than doubled the total number of flowers produced in all backgrounds tested, indicating that manipulation of NERD1 levels can be used to increase plant productivity.\n\nAuthor SummaryOvules are the precursors of seeds in flowering plants. Each ovule contains an egg cell and a central cell that fuse with two sperm cells during double fertilization to generate seeds containing an embryo and endosperm. The number of ovules produced during flower development determines the maximum number of seeds that can be produced by a flower. In this paper, we used natural variation in Arabidopsis thaliana accessions to identify regions of the genome that are associated with ovule number. Polymorphisms in the plant-specific NERD1 gene on chromosome 3 were significantly associated with ovule number. Mutant and overexpression analyses revealed that NERD1 is a positive regulator of ovule number, lateral branching, and flower number in Arabidopsis. Manipulation of NERD1 expression levels could potentially be used to increase yield in crop plants.

plant biology↗

bioRxiv2018

An Optically Decodable Bead Array for Linking Imaging and Sequencing with Single-Cell Resolution

Optically decodable beads link the identity of an analyte or sample to a measurement through an optical barcode, enabling libraries of biomolecules to be captured on beads in solution and decoded by fluorescence. This approach has been foundational to microarray, sequencing, and flow-based expression profiling technologies. We have combined microfluidics with optically decodable beads to link phenotypic analysis of living cells to sequencing. As a proof-of-concept, we applied this to demonstrate an accurate and scalable tool for connecting live cell imaging to single-cell RNA-Seq called Single Cell Optical Phenotyping and Expression (SCOPE-Seq).

systems biology↗

bioRxiv2018

β-lactam Antibiotics Stimulate the Pathogenicity of Methicillin-resistant Staphylococcus aureus Via SarA-controlled Tandem Lipoprotein Expression

Methicillin-resistant Staphylococcus aureus (MRSA) is a leading cause of nosocomial infections worldwide. MRSA resists nearly all {beta}-lactam antibiotics that have a bactericidal activity and a signal inducer effect. However, studies have yet to clarify whether the inducer effect of empirically used {beta}-lactams stimulates MRSA pathogenicity in vivo. Here, we showed that a new cluster of tandem lipoprotein genes (tlpps) was upregulated in MRSA in response to the subinhibitory concentrations of {beta}-lactam induction. The increased Tlpps significantly altered immune responses by macrophages with high IL-6 and TNF levels. The deletion of the tlpps mutant (N315{Delta}tlpps) significantly decreased the proinflammatory cytokine levels in vitro and in vivo. The bacterial loads of N315{Delta}tlpps in the mouse kidney were also reduced compared with those of the wild type N315. The {beta}-lactam-treated MRSA exacerbated cutaneous infections with increased lesion size, extended illness, and flake-like abscess-formation compared with those of the nontreatment. The {beta}-lactam antibiotics that promoted the MRSA pathogenicity were SarA dependent, and the increasing expression of tlpps after {beta}-lactam treatment was directly controlled by the global regulator SarA. Overall, our findings suggested that {beta}-lactams should be used carefully because it might lead to a worse outcome of MRSA infection than inaction in the treatment.\n\nAuthor summary{beta}-lactams are widely used in practice to treat infectious diseases, however, {beta}-lactams worsening the outcome of a certain disease is poorly understood. In this study, we have identified a new cluster of tandem lipoprotein genes (tlpps) that is upregulated in the major clinically prevalent MRSA clones in response to the subinhibitory concentrations of {beta}-lactams induction. The major highlight in this work is that {beta}-lactams induce SarA expression, and then SarA directly binds to the tlpp cluster promoter region and upregulates the tlpp expression in MRSA. Moreover, the {beta}-lactam stimulated Tlpps are important virulence factors that enhance MRSA pathogenicity. The deletion of the tlpps mutant significantly decreases the proinflammatory cytokine levels in vitro and in vivo. The {beta}-lactam induced Tlpps enhance the host inflammatory responses by triggering the expression of IL-6 and TNF, thereby promoting bacterial colonization and abscess formation. These data elucidate that {beta}-lactams can worsen the outcome of MRSA infection through the induction of tlpps that are controlled by the global regulator SarA.

pathology↗

bioRxiv2018

Nrf1D is the first candidate secretory transcription factor in the blood plasma, with its precursor existing as a unique redox-sensitive transmembrane CNC-bZIP protein in somatic tissues

Amongst multiple distinct isoforms, Nrf1D is synthesized from translation of an alternatively-spliced transcript of Nrf1 mRNA, with a naturally-occurring deletion of its stop codon-flanking 1466 nucleotides. This molecular event leads to the reading frameshift mutation, which results in a constitutive substitution of the intact Nrf1s C-terminal 72 amino acids (aa, covering the second half of the leucine zipper motif to C-terminal Neh3L domain) by an additional extended 80-aa stretch to generate a unique variant Nrf1D. The C-terminal extra 80-aa region of Nrf1D was identified to fold into a redox-sensitive transmembrane domain that enables it to be tightly integrated within the endoplasmic reticulum (ER) membranes. Notably, the salient feature of Nrf1D confers it to be distinguishable from prototypic Nrf1, such that Nrf1D is endowed with only a less ability than wild-type Nrf1 at mediating target gene expression. Further evidence has been presented revealing that both mRNA and protein levels of Nrf1D were detected to varying extents in somatic tissues. Surprisingly, we also found the existence of Nrf1D-derived isoforms in the blood plasma, implying that it is a candidate secretory transcription factor, although its precursor acts as an integral transmembrane-bound CNC-bZIP protein that entails dynamic topologies, before being unleashed from the ER to enter the blood plasma.

cell biology↗