Biology subjects

Nanan, R.

Publications and source records attributed to Nanan, R..

7 recordsLinked to original sources

bioRxiv2024

Multi-organ transcriptomic atlas reveals hallmarks of labor

Pregnancy and labor are dynamic processes involving various rapid biological changes. Previous studies found that during pregnancy there are gradual alterations in immune and metabolic pathways. In contrast, changes linked to labor are less well-known, generally limited to reports on specific differentially expressed genes, lacking a more comprehensive overview of changes of the overall signalling landscapes. Moreover, most previous works were standalone, based on individual organs. Here, we aimed to present a more systematic and holistic overview of the impacts of labor on both the maternal and fetal aspects. For this purpose, we collated a multi-organ transcriptomic atlas to decipher the influences of labor on multiple maternal and fetal compartments, covering the maternal adipose tissues (subcutaneous and visceral fat), peripheral blood, myometrium and placenta and fetal cord blood mononuclear cells (CBMCs), and spanning both physiological and pathological conditions. During labor, activation of pro-inflammatory TNF signaling was found in all maternal compartments except adipose tissues, which, along with myometrium, showed upregulation in glycolysis. Myc signaling, as a critical nexus within the intracellular signaling network, was generally enhanced in labor. Contrarily, fetal CBMCs in labor upregulated the anti-inflammatory TGF{beta} pathway. Importantly, changes in the maternal TNF signaling were conserved across the spectrum of healthy pregnancy of different parities, and pathological conditions like preterm pregnancy and smoking-affected pregnancy. Mechanistically, it might be explained by the reduction in progestin hormonal signals during labor but not by the mechanical stress. Collectively, we present a comprehensive multi-organ transcriptomic atlas elucidating the maternal and fetal immune and metabolic landscapes associated with labor, shedding light on the complex physiology.

physiology↗

bioRxiv2024

High fat low carbohydrate diet is linked to protection against CNS autoimmunity

Multiple sclerosis (MS) is a common central nervous system (CNS) autoimmune disease, and diets and nutrients are emerging as critical contributing factors. However, a comprehensive understanding of their impacts and the underlying mechanisms involved is lacking. Harnessing state-of-the-art nutritional geometry analytical methods, we first revealed that globally, increased carbohydrate supply was associated with increased MS disease burden, while fat supply had an opposite effect. Furthermore, in a preclinical MS mouse model, experimental autoimmune encephalomyelitis (EAE), we found that an isocaloric diet high in carbohydrate aggravated EAE, while a diet enriched in fat was fully protective. This was reflected by reduced neuroinflammation and skewing towards anti-inflammatory phenotypes, which involved transcriptomic, epigenetic and immunometabolic changes. We showcased that manipulating diets is a potentially efficient and cost-effective approach to prevent and/or ameliorate EAE. This exhibits translational potentials for intervention/prevention of MS and possibly other autoimmune diseases.

immunology↗

bioRxiv2024

The maternal and fetal metabolic and immune landscapes of gestational diabetes mellitus

ObjectivesGestational diabetes mellitus (GDM) is the most common pregnancy-related medical complication. It is characterized by the development of hyperglycaemia during pregnancy and is known to lead to higher risk of metabolic disorders and other pathologies in both mothers and offsprings. Some studies probed the impacts of GDM, focusing on specific organs like placenta or adipose tissue, but so far, a systematic overview is lacking. Here, we aimed to curate a comprehensive atlas from currently available transcriptomic data for GDM, to comprehensively unravel how GDM influences the metabolic and immune landscapes in affected pregnancy. MethodsRNA-sequencing (RNA-seq) data for maternal subcutaneous and omental fat, peripheral blood mononuclear cells (PBMCs), and fetal umbilical vein endothelial cells (HUVECs), amniocytes and cord blood mononuclear cells (CBMCs); and single-cell RNA sequencing (scRNA-seq) data for placenta and CBMCs were collated from previous publications. Comparative analyses and gene set enrichment analyses (GSEA) were carried out for the control versus GDM pregnancy. ResultsMaternal metabolic landscapes were consistently shifted by GDM, with reduced oxidative phosphorylation and fatty acid metabolism in maternal adipose tissues and PBMCs. GDM also caused inflammation solely in maternal subcutaneous fat. scRNA-seq analysis of placenta revealed that GDM reduced granulocytes and myelocytes but increased extravillous trophoblast cells. GDM also differentially impacted the metabolic and immune signals in different placental cell subsets. Contrarily, metabolisms in fetal compartments were minimally influenced by GDM. However, they consistently exhibited elevated inflammatory signals. ConclusionGDM differentially reprogrammed the maternal and fetal metabolisms and immunity.

cell biology↗

bioRxiv2023

Breastfeeding enhances intestinal gluconeogenesis in infants

ObjectivesBreastfeeding confers metabolic benefits to the infants, including reducing risks for metabolic syndromes such as obesity and diabetes later in life, but the underlying mechanisms is not yet fully understood. Hence, we aim to investigate the impacts of breastfeeding on the metabolic organs of infants. MethodsPrevious literatures directly studying the influences of breastfeeding on offsprings metabolic organs were comprehensively reviewed. A microarray dataset of intestinal gene expression comparing infants fed on breastmilk versus formula milk was reanalyzed. ResultsReanalysis of microarray data showed that breastfeeding significantly enhanced gluconeogenesis in infants intestine. This resembled observations in other mammalian species where breastfeeding also promoted gluconeogenesis. ConclusionsBreastfeeding enhances intestinal gluconeogenesis in infants, which may underlie its metabolic advantages through finetuning the metabolic homeostasis. Such effect seems to be conserved across species, hinting its biological significance.

physiology↗

bioRxiv2023

A unique human cord blood CD8+CD45RA+CD27+CD161+ T cell subset identified by flow cytometric data analysis using Seurat

Advances in single cell analysis, especially cytometric approaches, have profoundly innovated immunological research. This has resulted in an expansion of high dimensional data, posing great challenges for comprehensive and unbiased analysis. Conventional manual analysis thus becomes untenable, while most computational methods lack flexibility and interoperability, hampering usability. Here, for the first time, we adapted Seurat, a single cell RNA sequencing (scRNA-seq) analysis package, for end-to-end flow cytometric data analysis. We showcased its robust analytical capacity by analyzing the adult blood and cord blood T cell profiles, which was validated by Spectre, another cytometric data analysis package, and manual analysis. Importantly, a unique CD8+CD45RA+CD27+CD161+ T cell subset, was identified in cord blood and characterized using flow cytometry and scRNA-seq analysis from a published dataset. Collectively, Seurat possesses great potential for cytometric data analysis. It facilitates thorough interpretations of high dimensional data using a single pipeline, implementing data-driven investigation in clinical immunology.

immunology↗

bioRxiv2022

Clonal dynamics of SARS-CoV-2-specific T cells in children and adults with COVID-19

Children infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) develop less severe coronavirus disease 2019 (COVID-19) than adults. The mechanisms for the age-specific differences and the implications for infection-induced immunity are beginning to be uncovered. We show by longitudinal multimodal analysis that SARS-CoV-2 leaves a small footprint in the circulating T cell compartment in children with mild/asymptomatic COVID-19 compared to adult household contacts with the same disease severity who had more evidence of systemic T cell interferon activation, cytotoxicity and exhaustion. Children harbored diverse polyclonal SARS-CoV- 2-specific naive T cells whereas adults harbored clonally expanded SARS-CoV-2-specific memory T cells. More naive interferon-activated CD4+ T cells were recruited into the memory compartment and recovery was associated with the development of robust CD4+ memory T cell responses in adults but not children. These data suggest that rapid clearance of SARS-CoV-2 in children may compromise their cellular immunity and ability to resist reinfection. HIGHLIGHTSO_LIChildren have diverse polyclonal SARS-CoV-2-specific naive T cells C_LIO_LIAdults have clonally expanded exhausted SARS-CoV-2-specific memory T cells C_LIO_LIInterferon-activated naive T cells differentiate into memory T cells in adults but not children C_LIO_LIAdults but not children develop robust memory T cell responses to SARS-CoV-2 C_LI O_FIG O_LINKSMALLFIG WIDTH=177 HEIGHT=200 SRC="FIGDIR/small/478400v1_ufig1.gif" ALT="Figure 1"> View larger version (44K): org.highwire.dtl.DTLVardef@e9586org.highwire.dtl.DTLVardef@17aaf37org.highwire.dtl.DTLVardef@18575e0org.highwire.dtl.DTLVardef@fde4ae_HPS_FORMAT_FIGEXP M_FIG C_FIG

immunology↗

bioRxiv2020

Dietary protein increases T cell independent sIgA production through changes in gut microbiota-derived extracellular vesicles

Secretory IgA (sIgA) is a key mucosal component ensuring host-microbiota mutualism. Using nutritional geometry modelling in mice fed 10 different macronutrient-defined, isocaloric diets, we identified dietary protein as the major driver of sIgA production. Protein-driven sIgA induction was not mediated by T cell-dependent pathways or changes in gut microbiota composition. Instead, the microbiota of high-protein fed mice produced significantly higher quantities of extracellular vesicles (EV), compared to those of mice fed high-carbohydrate or high-fat diets. These EV activated TLR4 to increase the epithelial expression of IgA-inducing cytokine, APRIL, B cell chemokine, CCL28, and the IgA transporter, PIGR. We showed that succinate, produced in high concentrations by microbiota of high-protein fed animals, increased the generation of reactive oxygen species by bacteria, which in turn promoted EV production. This is the first report establishing a causal link between dietary macronutrient composition, gut microbial EV release and host sIgA response.

immunology↗