title: Prior vaccination prevents overactivation of innate immune responses during COVID-19 breakthrough infection

city: Stanford

first: Leslie

last: Chan

address: 300 Pasteur Dr Bldg S131, Grant

institute: Stanford University

summary: At this stage in the COVID-19 pandemic, most infections are 'breakthrough' infections that occur in individuals with prior immunity to SARS-CoV-2 through infection or vaccination. Understanding both innate and adaptive immune induction in the setting of breakthrough infection is critical to refining vaccine strategies to ensure long-term efficacy against emerging variants, yet existing studies have primarily focused on adaptive immune responses. Here, we performed single-cell transcriptomic, proteomic, and functional profiling of innate and adaptive immunity during primary and breakthrough COVID-19 infections by comparing immune responses between unvaccinated and vaccinated individuals during the SARS-CoV-2 Delta wave. Breakthrough infections were characterized by a significantly less activated transcriptomic profile in CD56dim NK cells and monocytes, with induction of pathways limiting NK cell proliferation and monocyte migratory potential. Furthermore, we observed a female-specific trend of increased transcriptomic activation of CD16+ monocytes and  type-2 conventional dendritic cells (cDC2s) during breakthrough infections. Despite these differences, antibody-dependent cellular cytotoxicity responses were similar between breakthrough and primary infection groups. These insights suggest that prior vaccination prevents overactivation of innate immune responses during breakthrough infections with discernible sex-specific patterns and underscore the potential of harnessing vaccines in mitigating pathologic immune responses resulting from overactivation.

overall_design: Single-cell RNA sequencing of peripheral blood mononuclear cells (PBMCs) from 25 unvaccinated, infected participants and 25 vaccinated, infected participants

first: Catherine

last: Blish


title: Reactivation of an Embryonic Cardiac Neural Crest Transcriptional Subcircuit During Zebrafish Heart Regeneration [scRNA-seq]

status: Public on Jan 30 2025

city: Berkeley

first: Megan

last: Martik

state: California

address: 163 Weill Hall

department: Molecular and Cell Biology

country: USA

institute: University of California Berkeley

type: Expression profiling by high throughput sequencing

summary: During vertebrate development, the heart primarily arises from mesoderm, with crucial contributions from cardiac neural crest cells that migrate to the heart and form a variety of cardiovascular derivatives.  Here, by integrating bulk and single cell RNAseq with ATAC-seq, we identify a gene regulatory subcircuit specific to migratory cardiac crest cells composed of key transcription factors egr1, sox9a, tfap2a and ets1. Notably, we show that cells expressing the canonical neural crest gene sox10 are essential for proper cardiac regeneration in adult zebrafish. Furthermore, expression of all transcription factors from the migratory cardiac crest gene subcircuit are reactivated after injury at the wound edge. Together, our results uncover a developmental gene regulatory network that is important for cardiac neural crest fate determination, with key factors re-activated during regeneration.

overall_design: mcherry+ cells from 16 somite-stage zebrafish embryos (migratory cardiac neural crest stage) were FAC-sorted from Tg(-4.9sox10:GAL4-UAS-cre;UAS:NfsB-mCherry;myl7:nucGFP) and analyzed using 10X Chromium Single Cell 3’ v3.1 sequencing.

first: Marianne

last: Bronner

first: Rekha

last: Dhillon-Richardson

first: Alexandra

last: Haugan

first: Luke

last: Lyons

first: Joseph

last: McKenna


title: miR-17/20a mitigates interstitial fibrosis by repressing Frmd6 expression in renal epithelia [miRNA-seq]

city: Ann Arbor

first: David

last: Turner

state: MI

address: 109 Zina Pitcher Place

department: Michigan Neuroscience Institute

institute: University of Michigan

type: Non-coding RNA profiling by high throughput sequencing

summary: In this study, we evaluated genetic mouse models of inducible renal epithelia-specific miR-17~92 loss-of-function and gain-of-function using unilateral ureteral obstruction. We utilized PAR-CLIP in HK2 cells to identify miR-17/-20a targets, which we subsequently validated in vitro. We examined expression of a novel miR-17/-20a target in human nephrectomy samples with varying degrees of fibrosis. We identify an activator of Hippo signaling, FERM domain-containing protein 6 (FRMD6, also known as Willin), as a novel miR-17/20a target. Frmd6 is upregulated in tubular epithelium of obstructed kidneys that lack miR-17~92, along with increased phosphorylation of Smad3 and STAT3, two known miR-17~92 profibrotic targets. Frmd6 overexpression is sufficient to result in elevated secretion of the extracellular matrix component collagen III in vitro. Finally, we demonstrate that FRMD6 expression is associated with collagen III expression in human nephrectomy samples.Our findings demonstrate that the miR-17~92 cluster in renal epithelia functions in an anti-fibrotic manner by regulating multiple pro-fibrotic pathways. We also identify Frmd6 as a novel miR-17/20a target in renal epithelia, which may drive renal fibrosis.

overall_design: miRNA-seq profiles of HK2 cells treated with TGF-beta compared to control cells.

middle: L

first: Markus

last: Bitzer

first: Huanqing

last: Zhang

first: Deborah

last: Walter


title: A metabolic switch orchestrated by IL-18 and the cyclic dinucleotide cGAMP programs intestinal tolerance

city: Seodaemun-gu

first: Insuk

last: Lee

state: Seoul

address: 50 Yonsei-ro

department: Biotechnology

country: South Korea

institute: Yonsei University

type: Genome binding/occupancy profiling by high throughput sequencing

summary: Tissues are exposed to diverse inflammatory challenges that shape future inflammatory responses. While cellular metabolism regulates immune function, how metabolism programs and stabilizes immune states within tissues and tunes susceptibility to inflammation is poorly understood. Here, we describe an innate immune metabolic switch that programs long-term intestinal tolerance. Intestinal interleukin-18 (IL-18) stimulation elicited tolerogenic macrophages by preventing their proinflammatory glycolytic polarization via metabolic reprogramming to fatty acid oxidation (FAO). FAO reprogramming was triggered by IL-18 activation of SLC12A3 (NCC), leading to sodium influx, release of mitochondrial DNA, and activation of stimulator of interferon genes (STING). FAO was maintained in macrophages by a bistable switch that encoded memory of IL-18 stimulation and by intercellular positive feedback that sustained the production of macrophage-derived 2'3'-cyclic GMP-AMP (cGAMP) and epithelial-derived IL-18. Thus, a tissue-reinforced metabolic switch encodes durable immune tolerance in the gut and may enable reconstructing compromised immune tolerance in chronic inflammation.

overall_design: We isolated nuclei from the whole colon tissues of IL-18bp-/- or WT mice 7 days after triggering endogenous IL-18 production using 0.5% DSS.

first: Peng

last: Xiao

first: Randall

last: Tyler Mertens

first: Aditya

last: Misra

first: Seungbyn

last: Baek

first: Martin

last: Hemberg

first: Roni

last: Nowarski


title: Genes Expression Analysis of Cervical Cancer-derived cells Treated with Metformin

status: Public on Jan 31 2025

city: Ciudad de México

first: Alfredo

last: Hidalgo-Miranda

state: CDMX

address: Periferico Sur #4809

department: Cancer Genomic

country: Mexico

institute: INMEGEN

summary:
NOD-SCID mouse were treated with metformin for 11 and 24 days, the gene expression of tumors of mice treated with metformin were compared with respect to the expression of the tumors of mouse treated with vehicle (water).
We evaluated the effect of Metformin (525mg/kg/day) for two times of treatment (11 days and 24 days) upon gene expression in tumors of mice treated or not with metformin. Metformin treatment decreased of tumor growth in both treatment regimens. A complete genomic analysis of transcriptomic status after treatment with metformin revealed an impact on the overall expression of transcripts.

overall_design: We analyzed expression profile of the mouse after treatment with Metfomin by 11 and 24 days versus mouse treatment with Vehicle (water), using the Affymetrix Human Transcriptome Array 2.0 platform. Array data was processed by Affymetrix  Computational Tool.

first: Karen

middle: G

last: De la Cruz-López

first: Alejandro

last: García-Carrancá

first: Patricio

last: Gariglio-Vidal

first: Elizabeth

last: Ortiz-Sanchez

first: Omar

last: Beltrán-Anaya Fredy

first: A

last: Valencia-González Heriberto


title: Wild-Type vs ORAI 2/3 DKO vs ORAI 1/2/3 TKO_Pathogenic Th17 cells_ 48h

city: Los Angeles

first: Yousang

last: Gwack

state: CA

address: 10833 Le Conte Ave

institute: Univeristy of California-Los Angeles

summary: Transicriptome comparison between murine WT, ORAI 2/3 DKO, and ORAI TKO pTH17cells at 48 hours following differentiation

overall_design: Naive CD4+ T-cells were isolated and purified from wild-type (control), ORAI 2/3 DKO, and ORAI 1/2/3 TKO mice. Naïve CD4+ T cells were enriched by magnetic sorting from single-cell suspensions generated by mechanical disruption of spleens and lymph nodes of adult mice using MagniSort naïve CD4+ T cell enrichment kit (catalog # 8804-6824-74,ThermoFisher Scientific). For effector T cell differentiation, cells were stimulated with anti-CD3 antibody (1452C11, Bio X Cell) and anti-CD28 antibody (Clone 37.51, Bio X Cell) for 48 hours on a plate coated with rabbit anti-hamster antibody (MP Biomedicals). CD4 + CD25 - T cells were cultured with anti-IL-4 antibody (Peprotech) and 10 μg/ml anti-IFN-γ antibody, 30 ng/ml IL-6 (Peprotech), 10 ng/ml IL-23 (R&D Systems) and 10 ng/ml IL-1β (R&D Systems) for pathogenic Th17 differentiation  in T cell medium. Cells were collected at 48h and prepared for bulk RNA sequencing analysis.

first: Beibei

last: Wu

first: Spyridon

last: Hasiakos

first: Shawn

last: Cokus

first: Matteo

last: Pellegrini

first: Sonal

last: Srikanth


title: Genome-wide methylation analysis of post-mortem cerebellum samples supports the role of peroxisomes in autism spectrum disorder

city: Hyderabad

first: Kommu

middle: Naga

last: Mohan

state: Hyderabad

address: Jawahar nagar

department: Biological Sciences

country: India

institute: Birla Institute of Technology and Science

summary: We tested the hypothesis that a subset of patients with autism spectrum disorder (ASD) contains candidate genes with high DNA methylation differences (effective values) that potentially affect one of the two alleles. Genome-wide DNA methylation comparisons were made on cerebellum samples from 30 patients and 45 controls. Twelve genes with high effective values, including GSDMD, MMACHC, SLC6A5 and NKX6-2, implicated in ASD and other neuropsychiatric disorders were identified. Monoallelic promoter methylation and downregulation were observed for SERHL (serine hydrolase-like) and CAT (catalase) genes associated with peroxisome function. These data are consistent with the hypothesis implicating impaired peroxisome function/biogenesis for ASD. A similar approach holds promise for identifying rare epimutations in ASD and other complex disorders.

overall_design: Genomic DNA samples isolated from 45 control and 30 autism cerebellum samples were subjected to Infinium 450 K methylation array analysis

first: Naga

last: Mohan Kommu


title: Khdc3 Regulates Metabolism Across Generations in a DNA-Independent Manner [small RNA-seq]

city: New York

first: Matthew

last: Smith-Raska

state: NY

address: 1300 York Ave.

department: Pediatrics

institute: Weill Cornell Medicine

summary: Genetic variants can alter the profile of heritable molecules such as small RNAs in sperm and oocytes, and in this manner ancestral genetic variants can have a significant effect on offspring phenotypes even if they are not themselves inherited.  Here we show that wild type female mice descended from ancestors with a mutation in the mammalian germ cell gene Khdc3 have hepatic metabolic defects that persist over multiple generations.  We find that genetically wild type females descended from Khdc3 mutants have transcriptional dysregulation of critical hepatic metabolic genes, which persist over multiple generations and pass through both female and male lineages.  This was associated with dysregulation of hepatically-metabolized molecules in the blood of these wild type mice with mutational ancestry.  The oocytes of Khdc3-null females, as well as their wild type descendants, had dysregulation of multiple small RNAs, suggesting that these epigenetic changes in the gametes transmit the phenotype between generations.  Our results demonstrate that ancestral mutation in Khdc3 can produce transgenerational inherited phenotypes, potentially indefinitely.

overall_design: Comparison of small RNAs from oocytes of wild type, Khdc3-null, and wild type mice generated from Khdc3-null grandfathers and wild type grandmothers (WT**(P)).

first: Natalie

last: Trigg

first: Liana

last: Senaldi


title: Single-nuclei RNA-seq analysis on utero-placental tissues

city: Newcastle Upon Tyne

first: Michael

last: Taggart

state: Tyne And Wear

address: International Centre for Life,

department: Biosciences Institute,

country: United Kingdom

institute: Newcastle University

summary: Tissues throughout the human body exert finely-tuned specific functions even when there is considerable overlap in the cellular constituents. Even when the major cellular component of tissues is the same – for example in the case of smooth muscle-rich tissues - discrete phenotypes are evident. Yet, the molecular expression profiles underpinning such specialised functionality is often unclear. This presents a challenge for introducing new medicinal therapies for pathophysiologies: can one target what makes tissue functionality unique without producing unwanted effects on the features that are similar. Such a scenario can be considered for the human uteroplacental unit. Ideally, one would like to target complications of pregnancy like pre-eclampsia (hypertension and proteinuria) or spontaneous preterm birth (early activation of parturition) by targeting particular types of smooth muscle tissues (e.g. arteries versus myometrium) without adversely affecting others. This situation is further complicated by the need to consider maternal and fetoplacental circumstances. Three smooth muscle-rich tissues of importance here are myometrium, maternal uterine (myometrial) arteries and placental arteries. Indeed, each display subtly distinct phenotypes suggesting that distinct molecular signatures may underlie these differences. Hence, we aimed to compare expression profiles of these three tissues to identify the underpinning molecular signatures using multi-omics approaches.

overall_design: To study transcriptome-wide expression of three smooth-muscle rich human utero-placental tissues, paired uterine biopsies and placentas were obtained, following written informed consent (LREC 10/H0906/71), from normal pregnant women undergoing elective Caesarean section at term (39-40 weeks gestation, n=4). Myometrial strips (M), myometrial arteries (MA) and placental chorionic plate arteries (PA) were each isolated, and cleaned of surrounding material, by careful microdissection, snap frozen in liquid N2 and stored at -80oC until further use. Comparative gene expression profiling analysis was carried using 10x single-nuclei RNA sequencing data generated from these three utero-placental tissues.

middle: J

first: Florence

last: Burte

first: Huei

middle: T

last: Ng

first: Julie


title: H3K27me3 epigenetic mark crucial for callus cell identity and regeneration capacity [RNA-seq]

status: Public on Jan 29 2025

city: Rehovot

first: Leor

middle: Eshed

last: Eshed Williams

address: P.O.Box 12

department: Faculty of Agriculture

country: Israel

institute: Hebrew university

summary:
Plant callus cells possess a remarkable ability to regenerate organs that often differ from their respective origins or even entire new individuals. Yet, the mechanisms underlying their pluripotent state remain elusive. We propose a strategy that involves two independent mechanisms to endow callus cells with pluripotency: (1) maintaining a unique transcriptional profile, characterised by the expression of genes from diverse developmental pathways that allows rapid response to developmental cues; (2) preventing premature differentiation through H3K27 methylation-mediated silencing of key transcription factors such as WUCHEL and SPEECHLESS. This strategy relies on a mechanism to silence the pluripotency network upon regenerative stimuli, enabling a single developmental pathway to dominate.
Our study reveals that the EMF2 complex, a key regulator of H3K27 tri-methylation, plays a crucial role in this process. Callus derived from the emf2 mutant, deficient in H3K27me3, exhibits severely impaired regeneration. Comparative analyses of chromatin states and transcription profiles between wild-type and emf2 calli revealed that the loss of EMF2 leads to upregulation of key transcription factors in callus, and identified the genes regulated solely by EMF2. Our findings suggest that suppressing pluripotency networks through H3K27me3 is essential for executing specific developmental programs to ensure effective regeneration.

overall_design: mRNA-seq profiling of wild-type Arabidopsis leaves, wild-type Arabidopsis callus, and emf2 mutant-derived callus


title: TNFAIP2 promotes NF-κB signaling mediate lymph node metastasis of oral squamous cell carcinoma by protecting IKKβ from ubiquitin proteasome degradation

city: Jinan

first: Teng

last: Xu

state: Shandong Province

address: 247 Beiyuan Street, Jinan, Shandong Province, People’s Republic of China

country: China

institute: Shandong University

summary: Tumor dissemination is a life-threatening event which confers to most cancer-related deaths with limited effective therapeutic option. TNFα-induced protein 2 (TNFAIP2) reveals pro-metastasis potential in several cancers. However, its definite role and underlying mechanism in oral squamous cell carcinoma (OSCC) is largely unknown. The impact of TNFAIP2 on tumor metastasis was assessed based on the conditional knockout mouse with 4-nitroquinoline-1-oxide (4NQO) induced OSCC through feature and immunohistochemistry analysis. To explore the specific mechanism and intervention means, enrichment analysis and co-immunoprecipitation were also applied, together with designing the nano-hydroxyapatite (nHAp) based RNA interference delivery system to restrict tumor dissemination. The epithelium conditional knockout Tnfaip2 reduced tumor initiation rate, differentiation degree and cervical lymph node metastasis (LNM) in mouse exposed to 4NQO. Enrichment analysis suggested NF-κB signaling was associated with these effects. Western blot proved that TNFAIP2 prevented the ubiquitin proteasome degradation of inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase beta (IKKβ), a classical transcriptional activator protein in NF-κB signaling. Mechanistically, it was demonstrated that TNFAIP2 completely interacted with kelch-like ECH-associated protein 1 (KEAP1) to avoid IKKβ from ubiquitination at K63 and subsequent proteasomal degradation, which finally sustained NF-κB signaling and facilitated tumor metastasis by enhancing epithelial-mesenchymal transition (EMT) and lymphangiogenesis. Notably, the synthetic small interfering RNA delivery systems nHAp@PLL-siTnfaip2 showed significant effect in attenuating tumor progression of OSCC mouse. Above results showed TNFAIP2 promoted the EMT and lymphangiogenesis of OSCC by regulating NF-κB signaling, a mechanism that was dependent on the interaction with KEAP1 completely. The nHAp based TNFAIP2 interference might serve as novel therapeutics in limiting OSCC metastasis.

overall_design: To explore the changes of transcriptome by TNFAIP2, CAL27 cells were divided into two groups: cells infected with control and cells infected with TNFAIP2-overexpressing plasmid. RNA-seq profiling the vector and TNFAIP2 overexpression CAL27 cells.

first: Yaning

last: Wang

first: Zechen

last: Zhao

first: Jinsong

first: Zhenyuan

first: Yuemei

last: Yang

first: Xiaomeng

last: Song

first: Qingguo

last: Lai


title: Decoding single-cell transcriptomic landscape and physiological roles of RUNX1 in macaque embryonic hematopoiesis

city: Beijing

first: Zhengyang

address: 8th Dongda street, Fengtai district

institute: Fifth Medical  Center of Chinese PLA General Hospital,

summary: Blood birth during embryogenesis consists of multiple waves generating diverse progenies and is governed by spatiotemporally specific mechanisms1. Despite extensive studies in animal models, our current understanding of embryonic hematopoiesis in primates is very limited, particularly regarding the physiological roles of the presumed key regulators. Here, we firstly constructed a comprehensive single-cell RNA-seq atlas of embryonic hematopoiesis in rhesus macaque, involving multiple hematopoietic tissues (yolk sac, aorta-gonad-mesonephros region and fetal liver). We revealed high conservation of hematopoietic cell types and gene regulatory networks between human and macaque, and demonstrated a previously unrecognized dual-path specification of fetal liver monocytes in primate embryos, namely directly from lymphoid-featured progenitors in addition to from canonical granulocyte–monocyte progenitors. By generating RUNX1-null macaque embryos through CRISPR–Cas9-based approach, we revealed the indispensable role of RUNX1 in formation of most blood lineages during primate embryogenesis. Of note, in the absence of RUNX1, besides the completely blocked endothelial-to-hematopoietic transition, mesenchymal-priming characteristics were found in the arterial endothelial cells from which hematopoietic stem cells should emerge. Taken together, this study presented the first in vivo evidence of molecular mechanism regulating embryonic hematopoiesis in primates, providing novel insights for decoding blood ontogeny and regeneration in human being.

sample_organism:
Macaca mulatta
Homo sapiens

platform_organism:
Macaca mulatta
Homo sapiens

overall_design: Here, we provided a single-cell transcriptome atlas of hematopoiesis  in human and rhesus macaque embryos using cells from hematopoietic tissues, including yolk sac, dorsal aorta and fetal liver. The developmental stage of human and macaque embryo span carnegie stage 10 to 15 and E28 to E34 respectively.

first: Yandong

last: Gong

first: Chenyang

last: Si

first: Chu

last: Chu


title: Systematic Discovery of Hidden Dynamics and Regulatory Codes in MAPK Signaling Networks

city: Boston

first: Jen

last: Sheen

state: MA

address: 185 Cambridge st. CPZN7620

department: Molecular Biology

institute: Massachusetts General Hospital

summary: Biological systems orchestrate complex, dynamic and interconnected signaling networks, which remain challenging to elucidate with static, redundant, deleterious or lethal mutations in multicellular genetic circuits. To uncover hidden regulatory mechanisms and resolve genotype-phenotype discrepancies of mitogen-activated protein kinases (MAPKs) as master signaling integrators, we combined systematic network analyses with quantitative chemical perturbations of genetically engineered MAPKs for signaling interrogation in Arabidopsis thaliana. We demonstrate specific, combinatorial, antagonistic, dynamic and ordered controls of the core MAPKs as the central hub for multi-stress signaling, immune switches, and cell-fate specification. Intertwined MAPK programs with time-based negative-feedbacks control multilayered innate immune responses. Threshold-sensitive MPK4 specifies opposite consequences in triggered-immunity or autoimmunity. MPK3/6 dictate master transcription factors in stem-cell niches to constrain leaf-epidermal and root-meristem reprogramming. Chemical genetic-based systems analyses in time, space, amplitude and developing cell types open new possibilities to reconstruct and discover signaling networks in broad contexts of live organisms.

overall_design: Genome-wide survey of 1) Flg22-triggered early response in wild type seedlings, 2) various stimuli (Flg22, Pep3, Mechanical wounding, UVB, H2O2, ABA, MeJA) response in wild type,impk36, and impk4 seedlings, 3) transcriptome network in adult plants of mpk4 and impk4 at various hours after inhibitor treatment

first: Hoo

middle: S

last: Chung

first: Matthew

last: McCormack

first: Woo

last: Sul


title: Khdc3 Regulates Metabolism Across Generations in a DNA-Independent Manner [WTMM, WTPP, HFP liver RNA-seq]

last: Smith-Raska

overall_design: Comparison of hepatic transcriptomes in genetically wild type female mice descended from either Khdc3-null maternal and paternal grandmothers (WT**(M)) or Khdc3-null maternal and paternal grandfathers (WT**(P)) with wild type female mice with all wild type ancestors (WT).

first: Liana

last: Senaldi


title: Khdc3 Regulates Metabolism Across Generations in a DNA-Independent Manner [liver]

overall_design: Comparison of hepatic transcriptomes in wild type (WT) and Khdc3-null (KO) mice of different genetic ancestries, at 8 weeks of age.  WT mice are descended from WT ancestors, while KO mice are descended from KO ancestors.  WT_star females are genetically WT mice descended from heterozygous parents and a combination of WT and KO grandparents, while KO_star females are genetically KO mice that are similarly descended from heterozygous parents and a combination of WT and KO grandparents


title: Protective effects of two different chaperones demonstrated in a mouse model of sporadic AD

city: Moscow

first: Alexander

middle: Pertovich

last: Rezvykh

state: Moscow

address: Vavilova, 32

department: Russian Academy of Sciences

country: Russia

institute: Engelhardt Molecular Biology Institute

summary: Previously, using various animal models of AD, we demonstrated the protective effect of intranasal administration of chaperones of such different structure as HSP70 and YB-1 at the level of animal’s behavior and functional state and morphology of different brain regions. We also described transcriptional changes in the brain of mice after bulbectomy (OBX mice) representing a model of sporadic AD with elements of major depression. Herein, we investigated the effects of recombinant HSP70 and YB1 sub-chronic administration on transcription in the hippocampus and cortex of the OBX mice. Both chaperones introduction caused significant changes in the transcription of the studied brain regions, partially reverting it to a pattern of the control sham operated mice. More than 60% of genes with altered transcription levels due to bulbectomy exhibited complete restoration of their normal expression levels after both chaperones treatment. Importantly, the number of genes with altered expression after chaperones treatment was twice as high in the hippocampus as in the cortex. The administration of the chaperones led to complete or partial normalization of the expression of many genes related to the metabolism of beta-amyloid and tau protein in the brain of OBX mice. Thus, both proteins reduced the expression of genes such as Kmt2d, Apba, Casp9, Sorl1, Ywhag, Ywhaz and others, that increased expression as a result of bulbectomy and in parallel compensatory increased the expression of such genes as Prepl, Pfdn2, Fbxl16, Nsf etc. Both chaperones normalized the expression of many genes involved in rRNA processing and ribosome biogenesis, as well as genes involved in the processes of neurotransmitter transport and secretion, cognition, apoptosis, ferroptosis and mitochondrial regulation. Thus, both chaperones normalized the expression of 47 genes involved in mitochondria function, including the expression of the Pet117 gene, responsible for the rate of oxygen consumption by mitochondria and the expression of Mgst1  gene which affects the protection of mitochondria from oxidative stress. Importantly, administration of YB-1 and Hsp70 normalized the expression of a number of genes involved in the formation of the cytoskeleton. A significant compensatory effect of both chaperones was demonstrated in all six cell types studied in the brain of OBX mice with the most pronounced effect observed in the astrocytes. Notably, besides genes specific for AD, administration of both proteins normalized the expression of a few genes specific for major depression altered in OBX mice and several genes implicated in the development of other neurodegenerative diseases.

overall_design: Single end polyA RNA-sequencing of brain tissues of mouse undergone olfactory bulbectomy after treatment with HSP70 or YB-1 proteins

first: Michaedl

last: Evgenev


title: Role of IL10 signaling in the circadian control of host response to Influenza infection

city: Philadelphia

first: Thomas

last: Brooks

address: 3400 Civic Center Blvd

department: ITMAT

institute: University of Pennsylvania

summary: The circadian clock confers a time-of-day specific protection against influenza A Virus (IAV) infection by regulating the host response and limiting immunopathology. IL10 is a cytokine with significant immunoregulatory functions; however, the role of IL10 in IAV is unclear, with reports of both benefit and harm from its blockade early during the infection. Since the expression of IL10R shows diurnal rhythmicity in the lungs, we tested if IL10 signaling contributes to time-of-day specific protection against IAV.

overall_design: Mice were intranasally infected with 30-35 PFU of mouse-adapted H1N1 (PR8) at either ZT11 or ZT23. To block IL-10 signaling, mice were treated with either IL-10R1a monoclonal antibody (Clone 1B1.3A, BioXCell BE0050) or polyclonal IgG (Clone MOPC-21, BioXCell BE0083) during the infection. Mice were treated with 100ug/10uL of IL10R1 MAb administered intranasally D0 in 10uL PBS, 150ug/100uL of IL10R1 Mab administered intraperitoneally on day 3 in 100uL of PBS, and 100ug/100uL of IL10R1 MAb administered i.p. D5.

first: Kaitlyn

last: Forrest

first: Martina

last: Towers

first: Oindrila

last: Paul

first: Hyeobin

last: Cho

first: Amruta

last: Naik

first: Yasmine

last: Issah

first: Mahendra Veeranna

last: Padmini

first: Hitesh

last: Deshmukh

first: Kristin

last: Hudock

first: Gregory

middle: R

last: Grant

first: Shaon

last: Sengupta


title: Khdc3 Regulates Metabolism Across Generations in a DNA-Independent Manner

first: Matthew

overall_design: Comparison of transcriptomes in Wild Type (WT) and Khdc3-null (KO) oocytes.


title: Exploiting cancer dormancy signaling mechanisms in epithelial ovarian cancer through spheroid and organoid analysis

city: London

first: Gabriel

middle: E

last: DiMattia

state: ONTARIO

address: 750 Base Line Rd E

department: Biochemistry

country: Canada

institute: Western University

summary: Epithelial ovarian cancer (EOC) exhibits a unique mode of metastasis, involving spheroid formation in the peritoneum. Our research on EOC spheroid cell biology has provided valuable insights into the signalling plasticity associated with metastasis. We speculate that EOC cells modify their biology between tumor and spheroid states during cancer dormancy, although the specific mechanisms underlying this transition remain unknown. Here, we present novel findings from direct comparisons between cultured EOC spheroids and organoids. Our results indicated that AMP-activated protein kinase (AMPK) activity was significantly upregulated and protein kinase B (Akt) was downregulated in iOvCa spheroids compared to organoids, suggesting a clear differential phenotype. Through a comprehensive RNA sequencing analysis, we further supported these phenotypic differences and highlighted the significance of cell cycle regulation in organoids. By inhibiting the G2/M checkpoint via kinase inhibitors, we confirmed that this pathway is essential for organoids. Interestingly, our results suggest that specifically targeting aurora kinase A (AURKA) may represent a promising therapeutic strategy since our cells were equally sensitive to Alisertib treatment as both spheroids and organoids. Our findings emphasize the importance of studying cellular adaptations of EOC cells, as there may be different therapeutic targets depending on the step of EOC disease progression.

overall_design: iOvCa cell lines were cultured as 3D in vitro spheroids or organoids and collected for bulk RNAsequencing analysis.

first: Emily

last: Tomas

first: David

last: Carter

first: Bart

last: Kolendowski

first: Trevor

last: Shepherd


title: Gene expression correlates with disability and pain intensity in patients with chronic low back pain and Modic changes in a sex-specific manner

city: Oslo

first: Maria

middle: Dehli

last: Vigeland

address: Kirkeveien 166

country: Norway

institute: Oslo University Hospital

summary: Chronic low back pain (cLBP) lacks clear physiological explanations, and the treatment options are of limited effect. Here, we elucidate the underlying biology of cLBP in a subgroup of patients with Modic changes type I (suggestive of inflammatory vertebral bone marrow lesions) by correlating gene expression in blood with patient-reported outcomes on disability and pain intensity and explore sex-differences. Patients were included from the placebo group of a clinical study on patients with cLBP and Modic changes. Blood was collected at the time of inclusion, after three months, and after one year, and gene expression was measured at all time points by high-throughput RNA sequencing. The patients reported disability using the Roland Morris Disability Questionnaire, and pain intensity was assessed as a mean of three scores on a 0-10 numeric rating scale: current LBP, worst LBP within the last two weeks, and mean LBP within the last two weeks. The gene expression profiles were then correlated to the reported outcomes. Changes in gene expression over time correlated significantly with changes in both disability and pain. The findings showed distinct patterns in men and women, with negligible overlap in correlated genes between the sexes. The genes involved were enriched in immunological pathways, particularly T cell receptor complex and immune responses related to neutrophils. Several of the genes harbour polymorphisms that previously have been found to be associated with chronic pain. Men and women had distinct sets of correlating genes, suggesting gender differences in the underlying biology of disability and pain in these patients.

first: Maria Dehli

first: Siri Tennebø

last: Flåm

first: Magnus Dehli

first: Manuela

last: Zucknick

first: Monica

last: Wigemyr

first: Lars Christian Haugli

last: Bråten

first: Elisabeth

last: Gjefsen

first: John-Anker

last: Zwart

first: Kjersti

last: Storheim

first: Linda Margareth

last: Pedersen

first: Benedicte Alexandra

last: Lie


title: Novel Transcripts of EMT Driving the Malignant Transformation of Oral Submucous Fibrosis [mRNA-seq]

city: Manipal

first: Raghu

last: Radhakrishnan

state: Karnataka

address: Madava Nagar, Manipal

department: Oral and Maxillofacial Pathology and Microbiology

institute: Manipal College of Dental Sciences, Manipal

summary: OSF is a chronic, progressive, fibrotic condition of the oral mucosa that carries an elevated risk of undergoing malignant transformation. We aimed to identify and validate novel genes associated with the regulation of epithelial to mesenchymal transition (EMT) in Oral submucous fibrosis (OSF). Genes regulating EMT were identified through differential gene expression analysis, with a LogFC threshold of -1 and +1, and padj value < 0.05, utilizing data retrieved from GEO datasets, TCGA-HNSC dataset and whole transcriptome data generated from tissue samples of OSF, OSFSCC (OSF associated with OSCC) and OSCC (Oral squamous cell carcinoma). The curated EMT genes were correlated with functional states of cancer, subjected to clustering to identify the candidate genes. The EMT genes, namely MMP9, SPARC and ITGA5 were identified to be the novel candidate genes. Comprehensive pathway analysis and immunohistochemical analysis confirmed their role in regulating EMT in OSF, OSCC, and OSFSCC. Integration of bioinformatics and proteomics led to the discovery of novel candidate genes regulating EMT. The significant role of candidate genes MMP9, SPARC, and ITGA5 observed in fibrosis and malignancy indicates a novel mechanism of transition from fibrosis associated type 2 EMT to type 3 EMT, driving OSF to malignancy.

overall_design: The mRNA sequencing of matched case-adjacent normal samples (MN)(n=2 each) of oral submucous fibrosis associated with oral squamous cell carcinoma (OSFSCC) was performed using HiSeq X Ten/Novaseq with the parameters of 2x100bp, 30M reads per sample.


title: Single-cell RNA-Seq Analysis to investigate the potential of epithelial stem cells from human small bronchi in the treatment of Idiopathic Pulmonary Fibrosis.

city: Shanghai

first: Tao

last: Ren

address: No. 600, Yi Shan Road

institute: Shanghai Jiao Tong University Affiliated Sixth People's Hospital

summary: Basal cells (BCs) are essential airway stem cells to maintain and repair the integrity of airway epithelium. We performed scRNA-seq to evaluate the cultured airway basal cell condition and heterogeneity between healthy control and IPF groups.  Similar distributions of BCs subpopulations were detected between healthy control and IPF groups. Through GO enrichment analysis, we found that a vast majority of cells defined as cluster A were highly expressing genes associated with normal cell functions such as cell proliferation and division. Despite a small portion of cluster B cells (approximately 4% of total) existing in IPF samples, this was attributed to a background ratio when compared with healthy controls. We next investigated the potential regulatory impact of transplanted BCs on host endogenous cells(Fibroblasts & Distal_ BCs) by analysis of scRNA-seq data. Our study reveals that epithelial stem cells from human small bronchi offer a potential for therapy of Idiopathic Pulmonary Fibrosis.

overall_design: BCs and  fibroblasts  were generated by deep sequencing, using BD Rhapsody Analysis pipeline (Version: 1.8).

first: Zeyu

last: Liu

first: Yue

last: Hong

first: Feng

last: Xu

first: Shan

last: Shan


title: Effect of SLC25A1 knockdown on gene expression during differentiation of human airway basal cells

city: Iowa City

first: Michael

last: Chimenti

state: IA

address: 431 Newton Road

department: Iowa Institute of Human Genetics

institute: University of Iowa

summary: To investigate the role of mitochondrial citrate export in differentiation of airway basal cells, we knocked down SLC25A1, the gene encoding mitochondrial citrate carrier.

overall_design: We then performed gene expression profiling analysis using data obtained from RNA-seq of 5 donors at three time points. Comparative gene expression profiling analysis of RNA-seq data for human airway basal cells and its SLC25A1 knockdown derivative (shSLC25A1)

first: Bo Ram

last: Kim

first: Eric

middle: B

last: Taylor

last: Welsh


title: A microglia-containing cerebral organoid model to study early life immune challenges [scRNA-seq]

city: NEW YORK

first: Alice

last: Buonfiglioli

address: 1468 Madison Avenue

institute: Icahn School of Medicine at Mount Sinai

summary: Prenatal infections and activation of the maternal immune system have been proposed to contribute to causing neurodevelopmental disorders (NDDs), chronic conditions often linked to brain abnormalities. Microglia are the resident immune cells of the brain and play a key role in neurodevelopment. Disruption of microglial functions can lead to brain abnormalities and increase the risk of developing NDDs. How the maternal as well as the fetal immune system affect human neurodevelopment and contribute to NDDs remains unclear. An important reason for this knowledge gap is the fact that the impact of exposure to prenatal risk factors has been challenging to study in the human context. Here, we characterized a model of cerebral organoids (CO) with integrated microglia (COiMg). These organoids express typical microglial markers and respond to inflammatory stimuli. The presence of microglia influences cerebral organoid development, including cell density and neural differentiation, and regulates the expression of several ciliated and mesenchymal cell markers. Moreover, COiMg and organoids without microglia show similar but also distinct responses to inflammatory stimuli. Additionally, IFN-γ induced significant transcriptional and structural changes in the cerebral organoids, that appear to be regulated by the presence of microglia. Specifically, interferon-gamma (IFN-γ) was found to alter the expression of genes linked to autism. This model provides a valuable tool to study how inflammatory perturbations and microglial presence affect neurodevelopmental processes.

overall_design:
To investigate the role of microglia during brain development.
Gene expression profileon a single cell level of COiMg and CO derived from different iPSC-donor lines.

first: Verena

last: Haage

first: Rebecca

last: Chiu

first: Ya

last: Zhang

first: Philip

last: De Jager

first: Lot

middle: D

last: De Witte


title: Using integrative bioinformatics approaches and machine‑learning strategies to Identify potential signatures for atrial fibrillation

city: hefei

first: FU

last: SHIHAO

address: No. 96 Jinzhai Road

institute: university of science and technology of china

summary: Atrial fibrillation (AF) is the most common tachyarrhythmia and seriously affects human health. Key targets of AF bioinformatics analysis can help to better understand the pathogenesis of AF and develop therapeutic targets. The left atrial appendage tissue of 20 patients with AF and 10 patients with sinus rhythm were collected for sequencing, and the expression data of the atrial tissue were obtained. Based on this, 2578 differentially expressed genes were obtained through differential analysis. Different express genes (DEGs) were functionally enriched on Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG), mainly focusing on neuroactive ligand-receptor interactions, neuronal cell body pathways, regulation of neurogenesis, and neuronal death，regulation of neuronal death, etc. Secondly, 14 significant module genes were obtained by analyzing the weighted gene co-expression network of DEGs. Next, LASSO and SVM analyzes were performed on the differential genes, and the results were in good agreement with the calibration curve of the nomogram model for predicting AF constructed by the weighted gene co-expression network key genes. The significant module genes obtained by the area under the ROC curve (AUC) analysis were analyzed. Through crossover, two key disease characteristic genes related to AF, HOXA2 and RND2, were screened out. RND2 was selected for further research, and qPCR verified the expression of RND2 in sinus rhythm patients and AF patients. Patients with sinus rhythm were significantly higher than those in AF patients. Our study shows that RND2 can be used as a new target for the diagnosis and treatment of AF.

overall_design: Analysis of differentially expressed genes in left atrial tissue of patients with atrial fibrillation and sinus rhythm after high-throughput sequencing

first: Shihao

last: Fu

first: Zian

last: Feng

first: Ao

last: Li

first: Zhiwei

last: Zhao


title: Diverse NKT cells regulate early inflammation and neurological outcomes after cardiac arrest and resuscitation

first: Ana

last: Villasenor Altamirano

address: 60 Fenwood Rd

department: Pulmonary and Critical Care

institute: Brigham and Women's Hospital, Harvard Medical School

summary: Neurological injury drives most deaths and morbidity among patients hospitalized for out-of-hospital cardiac arrest (OHCA). Despite its clinical importance, there are no effective pharmacological therapies targeting post-cardiac arrest (CA) neurological injury. Here we analyzed circulating immune cells from a large OHCA patient cohort, finding that lymphopenia independently associated with poor neurological outcomes. Single cell RNA-sequencing of immune cells showed that T cells with features of both innate T cells and natural killer (NK) cells were increased in patients with favorable neurological outcomes. We more specifically identified an early increase in circulating diverse NKT cells (dNKT) in a separate cohort of OHCA patients with good neurological outcomes. These cells harbored a diverse T cell receptor repertoire but were consistently specific for sulfatide antigen. In mice, we found that sulfatide-specific dNKT cells trafficked to the brain after CA and resuscitation. In the brains of mice lacking NKT cells (Cd1d-/-), we observed increased inflammatory chemokine and cytokine expression and accumulation of macrophages when compared with wild-type mice. Cd1d-/- mice also had increased neuronal injury, neurological dysfunction, and worse mortality after CA. To therapeutically enhance dNKT cell activity, we treated mice with sulfatide lipid after CA, showing that it improved neurological function. Together, these data show that sulfatide-specific dNKT cells are associated with good neurological outcomes after clinical OHCA and are neuroprotective in mice after CA. Strategies to enhance the number or function of dNKT cells may thus represent a treatment approach for CA.

overall_design: Cardiac arrest (CA) was induced in WT or CD1d KO ten-week-old male mice on C57BL/6J with 80 ug potassium chloride per g body weight, after 8 minutes of arrest, epinephrine and ches compressions were applied for resucitation. Nuclei was extracted from hippocampus region 24 hr post CA.

first: Edy Y.

first: Tomoyoshi

last: Tamura


title: miR-17/20a mitigates interstitial fibrosis by repressing Frmd6 expression in renal epithelia [RNA-seq]

city: Ann Arbor

first: David

last: Turner

address: 109 Zina Pitcher Place

institute: University of Michigan

summary: In this study, we evaluated genetic mouse models of inducible renal epithelia-specific miR-17~92 loss-of-function and gain-of-function using unilateral ureteral obstruction. We utilized PAR-CLIP in HK2 cells to identify miR-17/-20a targets, which we subsequently validated in vitro. We examined expression of a novel miR-17/-20a target in human nephrectomy samples with varying degrees of fibrosis. We identify an activator of Hippo signaling, FERM domain-containing protein 6 (FRMD6, also known as Willin), as a novel miR-17/20a target. Frmd6 is upregulated in tubular epithelium of obstructed kidneys that lack miR-17~92, along with increased phosphorylation of Smad3 and STAT3, two known miR-17~92 profibrotic targets. Frmd6 overexpression is sufficient to result in elevated secretion of the extracellular matrix component collagen III in vitro. Finally, we demonstrate that FRMD6 expression is associated with collagen III expression in human nephrectomy samples.Our findings demonstrate that the miR-17~92 cluster in renal epithelia functions in an anti-fibrotic manner by regulating multiple pro-fibrotic pathways. We also identify Frmd6 as a novel miR-17/20a target in renal epithelia, which may drive renal fibrosis.

overall_design: RNA-seq analysis of HK2 cells treated with TGF-beta compared to control cells.

first: Markus

last: Bitzer

first: Huanqing

first: Deborah

last: Walter


title: A microglia-containing cerebral organoid model to study early life immune challenges [Bulk RNA-seq]

first: Alice

overall_design:
To investigate the role of microglia during brain development and upon exposure of inflammatory molecules.
Comparative gene expression profile of COiMg and CO derived from different iPSC-donor lines and stimulated with different ligands.

first: Raphael

last: Kübler


title: miR-17/20a mitigates interstitial fibrosis by repressing Frmd6 expression in renal epithelia

summary: This SuperSeries is composed of the SubSeries listed below.

overall_design: Refer to individual Series


title: Serum miRNA expression in mice exposed to a high dose of ionizing radiation

city: Hirosaki

first: Mitsuru

last: Chiba

state: Aomori

address: 66-1 Hon-cho

department: Graduate School of Health Sciences

country: Japan

institute: Hirosaki University

summary: Exposure to high-doses of ionizing radiation (IR) leads to development of a strong acute radiation syndrome (ARS) in mammals. ARS manifests after a latency period and it is important to develop fast prognostic biomarkers for its early detection and assessment. Analysis of chromosomal aberrations in peripheral blood lymphocytes is the gold standard of biological dosimetry, but it fails after high doses of IR. Therefore, it is important to establish novel biomarkers of exposure that are fast and reliable also in the high dose range. Here, we investigated the applicability of miRNA levels in mouse serum.

overall_design: In the present study, the serum miRNA expression in the irradiated and non-irradiated mice (0 Gy and 7 Gy) were investigated using Agilent SurePrint G3 mouse miRNA microarray.


title: Expression data from cultured spermatogonia established from Cdkn1c conditional knockout mouse  testes

city: Kyoto

first: mito

last: shinohara

state: Kyoto

address: Sakyo-ku, Yoshida Konoe

department: Medicine

institute: Kyoto University

summary: Mice lacking Cdkn1c (p57) in spermatogonia were found to be congenitally infertile due to spermatogonia depletion. Transplantation experiments showed that Cdkn1c deficiency compromised spermatogonial stem cells (SSC) activity. SSCs undergo self-renewal division to sustain spermatogenesis, and it is possible to derive germline stem (GS) cell cultures by supplementing GDNF and FGF2. We examined the influence of Cdkn1c depletion on gene expression of GS cells. In this dataset, we include the expression data obtained from cultured spermatogonia (GS cells) derived from Cdkn1c(p57) floxed/floxed mice. Cdkn1c(p57) floxed/floxed GS cells were treated with adenovirus cre recombinase. Each group contains 3 biological replicates.

overall_design: GS cells were established from testes of 10 day old  mice of C57BL/6 and 129 strains. Total RNA samples were extracted with TRIzol reagent (Invitrogen) and purified using the RNeasy cleanup system (QIAGEN, Valencia, CA). cDNA libraries were generated using a TruSeq stranded mRNA library preparation kit (Illumina, San Diego, CA). Sequencing was performed using NextSeq550 (Illumina) with a single-read sequencing length of 76 bp. 6 Total samples were analyzed.

first: Mito

last: Kanatsu-Shinohara

first: Takashi

last: Shinohara


title: Differentially expressed miRNAs in SW1990 and PANC-1 cells following GLI1 cDNA transfection.

city: Xi 'an

first: Bing

last: Qi

state: Select

address: No. 1, Xinwang Road, Weiyang District

institute: Xi'an Medical University

summary:
Screening of differentially expressed miRNAs in SW1990 and PANC-1 cells following GLI1 cDNA transfection.
We independently transfected SW1990 and Panc-1 cells with Gli1 cDNA for mRNA and miRNA microarray analysis. The results unveiled significant differential expression patterns, with numerous miRNAs and mRNAs showing changes post-Gli1 transfection. Remarkably, miR-301a exhibited high expression in both SW1990 and Panc-1 cells transfected with Gli1 cDNA.

overall_design: Microarray analysis was performed on three samples each of SW1990 and PANC-1 cells with GLI1 overexpression.


title: miR-17/20a mitigates interstitial fibrosis by repressing Frmd6 expression in renal epithelia [PAR-CLIP]

overall_design: Identification of microRNA binding sites in RNAs from HK2 cells, in both control cells and cells treated with TGF-beta.

last: Zhang


title: Dataset of histone H3K4me2 modified genes in the liver of female Sprague-Dawleyrats with chronic antipsychotic drugs of olanzapine or clozapine

city: Wollongong

first: Yueqing

last: Su

address: Northfields Avenue

country: Australia

institute: University of Wollongong

summary: Epigenetic histone modificationshave been found to be associated with the development of metabolic disorders.However,the potential contribution of these modifications to metabolic disturbances induced by chronic treatment with second-generation antipsychotic drugs (SGAs) remains unclear. This study presents chromatin immunoprecipitation (ChIP) data on H3K4me methylation in hepatic tissue of rats treated with olanzapine or clozapine for 9 weeks.This dataset provides a comprehensive view of the effects of SGAs on H3K4me methylation in an animal model, offering new insights into the epigenetic mechanisms underlying SGAs-induced metabolic side effects.

overall_design: Thirty-six female Sprague-Dawley rats (200g- 220g) were purchased from the Animal Resource Centre (Perth, WA, Australia). After one week of environmental adaption, the rats were randomly assigned into three groups: olanzapine (3 mg/kg, b.i.d, orally, Zyprexa, Eli Lilly, Indianapolis, USA), clozapine (20mg/kg, b.i.d, orally, Clozaril, Novartis, Turkey), and vehicle (equivalent sweet cookie dough pellet without drugs) with 12 animals per group. The antipsychotic drugs were mixed into 300mg sweet cookie powder (30% cornflour, 30.9% sucrose, 15.5% casein, 8.4% minerals, 6.4% fibre, 6.3% gelatine, 1.6% vitamins) and appropriate water. Each animal was treated orallytwice a day (8:00 am and 8:00 pm, respectively) for nine weeks, as described previously (Liu et al., 2017). During the treatment, rats were observed to completely consume drugs pellet. Since the rats avoided taking the cookie pellet with clozapine after 3 days’ treatment, clozapine was delivered using a 1 ml syringe via the mouth, followed by an equivalent sweet cookie dough pellet without drugs to ensure the same amount of cookie pellets was consumed. All animals were housed individually in temperature-controlled room (220C) with a 24-hour lighting cycle (lights on 07:00-19:00), allowed to free access water and standard laboratory chow diet (containing 3.9kcal/g, 10% fat, 16% protein and 74% carbohydrate) throughout the experiment. Body weight, food intake and water consumption were recorded every week. Two hours after the final time treatment, all fasting rats were sacrificed by carbon dioxide asphyxiation. Liver tissues were dissected and frozen in liquid nitrogen immediately.

first: Jiamei

last: Lian

first: Chao

last: Deng


title: Right-brain expression-biased wnt3 is vital in maintaining normal language function via combined functional genomic and genetic analysis

first: Chen

last: Yanxi

address: No. 138, Dong'an Road, Xuhui District, Shanghai

institute: Fudan University

summary: Language is a unique human capability with limited molecular understanding due to the lack of animal models and technical constraints. Transcriptomics analysis offers a comprehensive view of gene expression in specific tissues, aiding the understanding of their functions. However, such patterns have been underexplored in language-related regions of the human brain. This study conducts a comprehensive transcriptomic analysis of 125 samples from 13 language-related Brodmann areas (BAs) in both hemispheres of five human postmortem brains. The expression landscape of human language-related regions is mapped, revealing higher expression in the right hemisphere, notably BA45 (Broca’s area) and BA3/1/2 (ventral sensory-motor cortex). Integrative analysis of differentially expressed genes and language-relevant genetic discoveries provides insights into the rs62060948 locus. The findings suggest that the rs62060948-MYC-WNT3 axis plays a crucial role in language function in BA44 of the right hemisphere. Behavior tests in mice show that Wnt3 knockdown in the right auditory cortex leads to abnormal behaviors, confirming that imbalanced Wnt3 expression impacts language function. Pathway analysis indicates that Wnt3 maintains nervous system development through neuron ensheathment. This study enhances understanding of the molecular mechanisms underlying human language function and identifies potential targets for language disorder therapies.

overall_design: To investigate the specific molecular changes in the auditory cortex of mice after WNT3 overexpressing, we used three control groups and  OE groups for RNA-seq analysis.


title: Differentially expressed mRNAs in SW1990 and PANC-1 cells following GLI1 cDNA transfection.

summary:
Screening of differentially expressed mRNAs in SW1990 and PANC-1 cells following GLI1 cDNA transfection.
We independently transfected SW1990 and Panc-1 cells with Gli1 cDNA for mRNA and miRNA microarray analysis. The results unveiled significant differential expression patterns, with numerous miRNAs and mRNAs showing changes post-Gli1 transfection. Remarkably, miR-301a exhibited high expression in both SW1990 and Panc-1 cells transfected with Gli1 cDNA


title: Chick Early Amniotic Fluid Alleviates DSS-induced Colitis in Mice via T cell Receptor Pathway

city: Wuxi

first: Fan

last: Chen

state: jiangsu

address: No. 1800 Lihu Avenue

department: Wuxi School of Medicine

institute: Jiangnan University

summary: To investigate the effect of early chicken embryo amniotic fluid on gene expression in mice with dextran sulfate sodium-induced ulcerative colitis.

overall_design: The changes of gene expression in ulcerative colitis mice treated with early chick embryo amniotic fluid were studied by high-throughput RNA sequencin.

first: KeJia

last: Wu


title: Expression Profile of New Marker Genes Involved in Differentiation of Canine Adipose-Derived Stem Cells into Osteoblasts and Chondrocytes

city: Poznań

first: Maurycy

last: Jankowski

address: Rokietnicka 7

department: Wielkopolska Center of Digital Medicine

country: Poland

institute: Poznan University of Medical Sciences

summary: Next-generation sequencing (RNAseq) analysis of gene expression changes during the long-term in vitro culture and osteogenic and chondrogenic differentiation of ADSCs remains to be important, as the analysis provides important clues toward employing stem cells as a therapeutic intervention. In this study, the cells were isolated from adipose tissue obtained during routine surgical procedures and subjected to 14-day in vitro culture and differentiation. The mRNA transcript levels were evaluated using the Illumina platform, resulting in the detection of 19,856 gene transcripts. The most differentially expressed genes (fold change >|2|, adjusted p value < 0.05), between day 1, day 14 and differentiated cell cultures were extracted and subjected to bioinformatical analysis based on the R programming language. The results of this study provide molecular insight into the processes that occur during long-term in vitro culture, osteogenic and chondrogenic differentiation of ADSCs, allowing the re-evaluation of the roles of some genes in MSC progression towards a range of lineages. The results improve the knowledge of the molecular mechanisms associated with long-term in vitro culture and differentiation of ADSCs, as well as providing a point of reference for potential in vivo and clinical studies regarding these cells' application in regenerative medicine.

overall_design: To investigate the changes in gene expression after the osteogenic and chondrogenic differentiation and prolonged in vitro culture, we isolated mesenchymal stem cells from canine adipose tissue samples. We then performed gene expression analysis using the data obtained from RNA-seq of four group of samples: early controls, late controls cultured for 14 days, osteo- and chondro-induced ASCs cultured for 14 days. Each group of samples consisted of three biological replicates.

first: Jankowski

last: Maurycy

first: Wąsiatycz

last: Grzegorz

first: Kempisty

last: Bartosz

first: Suchodolski

last: Michał

first: Stefańska

last: Katarzyna

first: Dompe

last: Claudia


title: Gene expression profile at single cell level of duizhaozu1, duizhaozu2 and zhiliaozu1, zhiliaozu2.

first: zhen

last: zhu

address: huanhuxisan road 222

institute: shanghai jiao tong university

summary: We used single cell RNA sequencing (scRNA-seq) to analyze the diversity of kidney cell.

overall_design: According to whether treated with losartan or not, the mouse kidneys were divided into four specimens: duizhaozhu1, duizhaozhu2, zhiliaozhu1, and zhiliaozhu2, and analyzed using scRNAseq

first: Jianping

last: Ye

first: Li

last: Wei

first: Zhen

last: Zhu

first: Guangxin

last: Luan


title: DNA Methylation Profiling at Base-Pair Resolution Reveals Unique Epigenetic Features of Early-Onset Colorectal Cancer in Underrepresented Populations

city: Houston

first: Lanlan

last: Shen

state: TX

address: 1 Baylor Plz

institute: Baylor College of Medicine

type: Methylation profiling by high throughput sequencing

summary: Background. The incidence of early-onset colorectal cancer (EOCRC) has been rising at an alarming rate in the United States, and EOCRC disproportionately affects racial/ethnic minorities. Here, we construct comprehensive profiles of EOCRC DNA methylomes at base-pair resolution for a cohort of Hispanic and African American patients. Results. We show the epigenetic landscape of these EOCRC patients differs from that of late-onset colorectal cancer (LOCRC) patients, and methylation canyons in EOCRC tumor tissue preferentially overlapped genes in cancer-related pathways. Furthermore, we identify epigenetic alterations in metabolic genes that are specific to our racial/ethnic minority EOCRC cohort but not Caucasian patients from TCGA. Top genes differentially methylated between these cohorts included the obesity-protective MFAP2 gene as well as cancer risk susceptibility genes APOL3 and RNASEL. Conclusions. In this study, we provide to the scientific community high-resolution DNA methylomes for a cohort of EOCRC patients from underrepresented populations. Our exploratory findings in this cohort highlight epigenetic mechanisms underlying the pathogenesis of EOCRC and nominate novel biomarkers for EOCRC in underrepresented populations.

overall_design: Whole-genome bisulfite sequencing of microdissected early-onset colorectal cancer tumors and normal adjacent colonic mucosal tissue from FFPE preserved tissues.

first: Karen

last: Riggins

first: Jason

last: Li

first: Wei

first: Chad

last: Creighton

last: Yang

first: Chaorong

first: Patricia

last: Castro

first: Wedad

last: Alfarkh

first: Neda

last: Zarrin-Khameh

first: Michael

last: Scheurer

first: Benjamin

last: Musher


title: Hypoxia impairs decitabine-induced expression of HLA-DR in acute myeloid leukaemia cell lines [RNA-seq]

city: Newcastle

first: Heather

last: Lee

state: NSW

address: University Drive, Callaghan

institute: The University of Newcastle

summary: Background Hypomethylating agents (HMA), such as azacytidine (AZA) and decitabine (DAC), are epigenetic therapies used to treat some patients with acute myeloid leukaemia (AML) and myelodysplastic syndrome (MDS). HMAs act in a replication-dependent manner to remove DNA methylation from the genome. However, AML cells targeted by HMA therapy are often quiescent within the bone marrow, where oxygen levels are low. In this study, we investigate the effects of hypoxia on HMA responses in AML cells.  Results AML cell lines (MOLM-13, MV-4-11, HL-60) were treated with DAC (100nM) or AZA (500-2000nM) in normoxic (21% O2) and hypoxic (1% O2) conditions. Hypoxia significantly reduced AML cell growth and colony-forming capacity across all cell lines, with no additional effects observed upon HMA treatment. Hypoxia had no impact on the extent of DNA hypomethylation induced by DAC treatment, but limited AZA-induced loss of methylation from the genome. Transcriptional responses to HMA treatment were also altered, with HMAs failing to up-regulate antigen presentation pathways in hypoxia. In particular, cell surface expression of the MHC class II receptor, HLA-DR, was increased by DAC treatment in normoxia, but not hypoxia. Conclusion Our results suggest that HMA-induced antigen presentation may be impaired by hypoxia. This study highlights the need to consider microenvironmental factors when designing co-treatment strategies to improve HMA therapeutic efficacy.

overall_design: Leukaemic cell lines (MOLM-13) were pre-exposed to either normoxic or hypoxic conditions, followed by treatment with hypomethylating agents (HMAs) or without (untreated) as controls. Each condition has three replicates. RNA was isolated from samples after completion of the experiment and assessed by RNA-seq.

first: Sam

last: Humphries

first: Sean

middle: M

last: Burnard

first: Courtney

last: Eggins

first: Simon

last: Keely

first: Danielle

last: Bond


title: Effect of hsa_circ_0001599 on gene expression during odontogenic differentiation of human dental pulp stem cells

city: Guangzhou

first: Junkai

last: Zeng

state: Guangdong

address: Southern Medical University

institute: Southern Medical University

summary: Dental pulp regeneration is significantly aided by human dental pulp stem cells (hDPSCs). An increasing number of studies have demonstrated that circular RNAs (circRNAs) are crucial in the multidirectional differentiation of many mesenchymal stem cells, but their specific functions and mechanisms remain unknown. This work aimed at elucidating the molecular mechanism by which hsa_circ_0001599 works in hDPSCs during odontogenic differentiation. The expression of hsa_circ_0001599 in hDPSCs and dental pulp tissue was determined by using quantitative real-time PCR (qRT‒PCR). The role of hsa_circ_0001599 in the odontogenic differentiation of hDPSCs and its mechanism were studied using a variety of in vivo and in vitro assessments. The odontogenic differentiation of hDPSCs was facilitated by the overexpression of hsa_circ_0001599, which activated the PI3K/AKT signalling pathway in vitro. In vivo, hsa_circ_0001599 can promote the formation of new dentin-like structures. Mechanistically, hsa_circ_0001599 enhanced ITGA2 expression by sponging miR-889-3p. Furthermore, hsa_circ_0001599 interacts with the methylation reader hnRNPA2B1, promoting hnRNPA2B1 translocation from the nucleus to the cytoplasm and increasing ITGA2 mRNA stability. This research revealed the important role of hsa_circ_0001599 in odontogenic differentiation. Thus, hDPSCs engineered with hsa_circ_0001599 have the potential to be effective therapeutic targets for dental pulp repair and regeneration

overall_design: RNA-seq profiling of dental pulp stem cells that have been genetically modified to overexpress hsa_circ_0001599 and the negative control (LV-circ1599 and LV-NC).

first: Yeqing

first: Chong

last: Jiang

first: Buling

last: Wu

first: Ming

last: Chen


title: Identification of pig olfactory receptors responding to androstenone and the key structure determinant

city: Chengdu

first: Pei-Dong

address: 211 Gongping street

institute: Sichuan Agricultural University

summary: Olfactory receptors are members of the transmembrane G protein-coupled receptor superfamily, playing crucial role in odor recognition which further mediates crucial biological processes in mammals. In sows, androstenone can trigger sexsual behaviors through olfaction, but the underlying mechanism remains to be explored. To identify the olfactory receptor responding to androstenone, we adapted the high-throughput RNAseq strategy to screen the altered genes upon androstenone treatment in olfactory epithelium of pig, yielding 1397 downregulated genes. Of which, 15 OR genes and 49 ORs-like genes are candidate androstenone responsive genes, and 6 ORs (OR2D2, OR7D4, OR8D1, OR8D2, OR10Z1 and OR7D4) were proved are responsible to androstenone mediated olfaction in vitro. Among the 6 ORs, pig OR7D4 has the highest level of androstenone response. To further find the structural determinant, we performed ligand-binding cavity analysis on pig OR7D4 with androstenone, predicted seven potential structural sites and further confirmed F178 and T203 are the key sites for recognizing androstenone. Nevertheless, the natural non-synonymous mutation M133V (rs696400829) of pig OR7D4 was proved can significantly impair the respondence to androstenone. This is the first time identified the ORs responding to androstenone in pig and the key structural determinant of pig OR7D4, which highlights the significance to investigate the role of OR7D4 on pig reproduction performance in future.

overall_design:
We screened for olfactory receptor genes that may respond to androstenone in the pig genome based on transcriptomic approach previously applied to species such as mice. Four sows which were offspring of Landrace (♂) and Rongchang pig (♀), aged 8 months, were divided into androstenone-treatment group and control group with two in each group. In the androstenone-treatment group.
The Boarmate, which mainly contains androstenone, was sprayed on the nasal cavity before slaughter, while the control group received no solution treatment before slaughter. After 30 mins, the sows were sacrificed, olfactory epithelium from left and right side were collected from each sow. Samples were used for preparation of RNA-seq libraries, the candidate olfactory receptor genes responding to androstenone were screened via the RNA-seq data.

first: Peidong

first: Shuqi

first: Tingting

last: Luo

first: Anjing

last: Zhang

first: Li

first: Jinyong

last: Wang

first: Yongju

last: Zhao

first: Zhining

last: Zhong

first: Xuemin

last: Li

first: Ziyin

last: Han

first: Jideng

last: Ma

first: Long

last: Jin

first: Keren

last: Long

first: Mingzhou

first: Lu

last: Lu


title: Immunohistochemical Profiling of Histone Modification Biomarkers Identifies Subtype-Specific Epigenetic Signatures and Potential Drug Targets in Breast Cancer

city: xian

first: Xi

state: Shannxi province

address: Northwest University, 229 North Taibai Road, Xi'an

department: 1 School of Life Science, Northwest University, Xi'an, Shaanxi 710069, China 2 Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, School of Medicine, Northwest University, Xi'an, Shaanxi 710069, China

institute: Northwest University

summary: Our findings provide a foundation for developing subtype-specific epigenetic therapies across distinct subtypes of breast cancer context, with a holistic view of how G9a inhibitor reshape the epigenetic landscape, affecting gene expression across multiple pathways. This helps in distinguishing beneficial effects, like tumor suppression, from potential risks, such as immune suppression or toxicity. This study highlights subtype-specific epigenetic regulators and validates G9a as a promising therapeutic target, particularly for TNBC. The findings provide a foundation for developing targeted epigenetic therapies to improve outcomes for aggressive BC subtypes.

overall_design: RNA-seq profilig of wildtye and G9a inhibitor UNC0642 treated  MCF7 cells、MDA-MB-231 cells、MDA-MB-468 cells .


title: Effect of SLC25A1 knockdown on chromatin accessibility during differentiation of human airway basal cells

first: Henry

last: Keen

address: 329 EMRB

institute: University of Iowa

summary:
To investigate the role of mitochondrial citrate export in differentiation of airway basal cells, we knocked down SLC25A1, the gene encoding mitochondrial citrate carrier.
We then performed chromatin accessibility profiling analysis using data obtained from ATAC-seq of 5 donors at three time points.

overall_design: Comparative chromatin accessibility profiling analysis of ATAC-seq data for human airway basal cells and its SLC25A1 knockdown derivative (shSLC25A1)

first: Bo Ram

last: Kim

first: Michael

last: Chimenti

first: Eric

last: Taylor

last: Welsh


title: RNA-seq and ATAC-seq data from pig jejunum with high and low feed efficiency

city: Wuhan

first: yi

last: huang

address: No.1 Shizishan Street, Hongshan District

institute: Huazhong Agricultural University

summary: Feed efficiency (FE) is a crucial trait in pig production that influences both economic viability and environmental sustainability. The jejunum, an essential organ for nutrient absorption, plays a significant role in determining FE by affecting how pigs process and utilize feed. To explore the genetic and regulatory mechanisms behind FE, we conducted an integrative multi-omics study using RNA sequencing (RNA-seq) and ATAC sequencing (ATAC-seq) on pigs with high and low FE. By comparing gene expression and chromatin accessibility profiles in the jejunum, we identified key differentially expressed genes (DEGs) and differentially accessible regions (DARs) associated with lipid metabolism and immune function, both of which are critical pathways for efficient growth. Notably, we identified transcription factors such as GATA4 and EHF and genes like SCARB1 and GRXCR1 that may play regulatory roles in FE. Our findings provide novel insights into the molecular mechanisms governing FE in pigs, offering potential targets for genetic selection and nutritional interventions to enhance feed efficiency and sustainability in pig production.

overall_design: To investigate the genetic and regulatory mechanisms behind feed efficiency, we generated both RNA sequencing (RNA-seq) and ATAC sequencing (ATAC-seq) datasets from jejunum of pigs with high and low feed efficiency.

first: Yue

last: Xiang

first: Yaobang

last: Jian

first: Jiahui

last: Sun

first: Yi

last: Huang

first: Saixian


title: Transcriptional time-course analysis during ash dieback infection revealed different responses in tolerant and susceptible Fraxinus excelsior genotypes

city: Göttingen

first: Victor

last: Chano

address: Buesgenweg 2

department: Forest Genetics and Forest Tree Breeding

country: Germany

institute: University of Göttingen

summary: Hymenoscyphus fraxineus, the causal agent of Ash Dieback (ADB), has been introduced to eastern Europe in the 1990s from where it spread causing decline in European ash populations. However, the genetic basis of the molecular response in tolerant and susceptible ash trees to this disease is still largely unknown. We performed RNA-sequencing to study the transcriptomic response to the disease in four ash genotypes (ADB-tolerant FAR3 and FS36, and ADB-susceptible UW1 and UW2), during a time-course of 7, 14, 21, and 28 days post-inoculation, including mock-infected trees as control samples for each sampling time point. The analysis yielded 395 and 500 Differentially Expressed Genes (DEGs) along the response for ADB-tolerant FAR3 and FS36, respectively, while ADB-susceptible UW1 and UW2 revealed 194 and 571 DEGs, respectively, with most DEGs found exclusively in just one of the genotypes. DEGs shared between tolerant genotypes FAR3 and FS36, included genes involved in the production of phytoalexins and other secondary metabolites with roles in plant defense. Moreover, we identified an earlier expression of genes involved in both pattern- and effector-triggered immunity (PTI and ETI) in ADB-tolerant genotypes, while in ADB-susceptible genotypes both responses were delayed (late response). Overall, these results revealed different transcriptomic expression patterns not only between ADB-tolerant and ADB-susceptible genotypes, but also within these two groups. This hints to individual response in the natural tolerance to ADB, possibly revealing diversified strategies across ash genotypes.

overall_design: This study included a experimental design with inoculated and mock-inoculated samples (2 conditions) from 4 ash genotypes (FAR3 and FS36 showing tolerance to the disease, and UW1 and UW2 showing susceptbility). Trees were sampled at 4 time points (7, 14, 21 and 28 days post inoculation or dpi), and for each of the groups 3 biological replicates were used. Therefore, the complete multifactorial design included RNA 96 samples (2 x 4 x 4 x 3).

first: Renata

last: Callegari Ferrari

first: Tania

last: Dominguez-Flores

first: Karuna

last: Shrestha

first: Barbara

last: Fussi

first: Hannes

last: Seidel

first: Oliver

last: Gailing

first: Katharina

last: Budde


title: Se-methyselenocysteine inhibits inflammatory response in an LPS stimulated chicken HD11 macrophage-like cells model through the NFKB2 pathway

city: Jingzhou

first: Tinghua

address: Jingmi Road #266

institute: Yangtze University

summary: We used LPS-stimulated chicken HD11 macrophage-like cell as a model to identify the key transcription factors involved in transcriptome regulation responsible for SeMC treatment. RNA-seq identified 3,263 transcripts significantly differentially expressed between the SeMC treated group and the control group, and 1,344 transcripts significantly differentially expressed between LPS+SeMC and LPS treated group (FDR < 0.05, FDR > 1.5). Bioinformatic analysis revealed that six transcription factors, NFKB2, RFX2, E2F5, ETV5, BACH1, and E2F7 were candidate genes for transcriptome regulation in SeMC treated HD11 cells.

overall_design: The samples for RNA-seq experiment were collected from four treatment groups with three replicates for each group, the SeMC (Se-methyselenocysteine)+PBS, SeMC+LPS, LPS and Control (PBS).

first: Min

last: Yao


title: Activation of a helper NLR by plant and bacterial TIR immune signaling

city: shang hai

first: hua

last: yu

state: FengLin

institute: CAS Center for Excellence in Molecular Plant Sciences

summary: Toll/interleukin-1 receptor (TIR) domains across different life kingdoms possess NADase activities and produce distinct small molecules including phosphoribosyl adenosine monophosphate/diphosphate (pRib-AMP/ADP) and two cyclic ADPR (cADPR) isomers 2’cADPR and 3’cADPR. Plant intracellular nucleotide-binding leucine-rich repeat (NLR) receptors with an N-terminal TIR domain sense pathogen effectors to initiate immune signaling and rely on downstream helper NLRs to execute immune function. Lipase-like proteins EDS1 and PAD4 transduce immune signals from sensor TIR-NLRs to a helper NLR called ADR1. We report the structure and function of Arabidopsis EDS1-PAD4-ADR1 (EPA) heterotrimer in complex with pRib-AMP/ADP activated by plant or bacterial TIR signaling. Bacterial TIRs that produce 2’cADPR, but not 3’cADPR, induce EPA complex formation and activate EPA signaling using pRib-AMP as the signaling molecule. 2’cADPR is hydrolyzed into pRib-AMP in vivo. 2’cADPR, but not 3’cADPR, induces EPA-dependent defense genes expression. Our findings shed light on the activation mechanisms of ADR1 by EDS1-PAD4 involving two structurally-related molecules with 2’cADPR likely being the storage form of the unstable signaling molecule pRib-AMP, as well as cross-talks between plant and bacterial TIR immune signaling.

overall_design: To investigate the function of 2'cADPR  and its dependence on EDS-PAD4-ADR1 pathway, we take a treatment of Col-0 Arabidopsis and PAD4 Knock out mutant with mock and 2'cADPR. Then  comparative gene expression profiling analyses were conducted using RNA-seq data of tissues above.

first: Hua

last: Yu

first: Li

last: Wan


title: Comprehensive analysis of microRNA after moderate intensity exercise in mice

city: Kamakura

first: Satoshi

last: Kondo

state: Kanagawa

address: Tebiro 6-10-1

department: New Projects Development Division

institute: Toray Industries,Inc.

summary: Moderate exercise is important for health; however, individuals differ in moderate intensity and it is difficult to identify. The purpose of this study was to identify new objective indicators to determine effective exercise intensity.

overall_design: The mice were randomly divided into the three groups: normal caged mouse group (control group, n = 3), aerobic exercise group (AE group, n = 3), and resistance exercise group (RE group, n = 3). The mice in AE group and RE group were exercised in each effective intensity and blood samples were obtained. Total RNA was isolated and analyzed using 3D-Gene miRNA Labeling kit and 3D-gene Human miRNA Oligo Chip (Toray Industries, Inc., Kanagawa, Japan).

first: Junpei

last: Hatakeyama

first: Shota

last: Inoue

first: Daisuke

last: Takamura

first: Hideki

last: Moriyama


title: Whole blood transcriptome profile identifies motor neurone disease (MND) RNA biomarker signatures

city: Perth

first: Sulev

last: Koks

state: Western Australia

address: 90 South Street

department: Centre for Molecular Medicine and Innovative Therapeutics

institute: Murdoch University

summary: (1) Background: Blood-based biomarkers for motor neuron disease are needed for better di-agnosis, progression prediction, and clinical trial monitoring. We used whole blood-derived total RNA and performed whole transcriptome analysis to compare the gene expression pro-files in (motor neurone disease) MND patients to the control subjects. (2) Methods: We com-pared 42 MND patients to 42 aged and sex-matched healthy controls and described the whole transcriptome profile characteristic for MND. In addition to the formal differential analysis, we performed functional annotation of the genomics data and identified the molecular path-ways that are differentially regulated in MND patients. (3) Results: We identified 12,972 genes differentially expressed in the blood of MND patients compared to age and sex-matched con-trols. Functional genomic annotation identified activation of the pathways related to neuro-degeneration, RNA transcription, RNA splicing and extracellular matrix reorganisation. (4) Conclusions: Blood-based whole transcriptomic analysis can reliably differentiate MND pa-tients from controls and can provide useful information for the clinical management of the disease and clinical trials.

overall_design: Total RNA from whole blood (TEMPUS tubes), 42 MND patients and 42 heathy controls.

last: Kõks

first: Karin

last: Rallmann

first: Mari

last: Muldmaa

first: Jack

last: Price

first: Abigail

last: Pfaff

first: Pille

last: Taba


title: Cryopreserved human alternatively activated macrophages promote resolution of acetaminophen-induced liver injury in mouse

city: Edinburgh

first: Stuart

last: Forbes

address: 5 Little France Drive

department: Centre for Regenerative Medicine

institute: The University of Edinburgh

summary: Acute liver failure (ALF) is a rapidly progressing, life-threatening condition most commonly caused by an overdose of acetaminophen (paracetamol). The antidote, N-acetylcysteine (NAC), has limited efficacy when liver injury is established. If acute liver damage is severe, liver failure can rapidly develop with associated high mortality rates. We have previously demonstrated that alternatively activated macrophages are a potential therapeutic option to reverse acute liver injury in pre-clinical models. In this paper we present data using cryopreserved human alternatively activated macrophages (hAAMs) - which represent a potential, rapidly available, treatment suitable for use in the acute setting. In a mouse model of APAP-induced injury, peripherally injected cryopreserved hAAMs reduced liver necrosis, modulated inflammatory responses, and enhanced liver regeneration. hAAMs were effective even when administered after the therapeutic window for N-acetylcysteine. This cell therapy approach represents a potential treatment for APAP overdose when NAC is ineffective because liver injury is established.

overall_design: Liver tissue was taken from C57BL/6J mice for RNA sequencing. Mice were either untreated (control; n=3), or treated with 350 mg/kg APAP. APAP-treated animals were given either PBS vehicle (n=5) or hAAM cells (n=4).

first: Maria Elena

last: Candela

first: Melisande

last: Addison

first: Rhona

last: Aird

first: Tak-Yung

last: Man

first: Jennifer

middle: A

last: Cartwright

first: Candice

last: Ashmore-Harris

first: Alastair

last: Kilpatrick

first: Philip

last: Starkey Lewis

first: Anna

last: Drape

first: Mark

last: Barnett

first: Donna

last: Mitchell

first: Colin

last: McLean

first: Neil

last: McGowan

first: Marc

last: Turner

first: James

middle: W

last: Dear


title: The emergence of DNAM-1 as the facilitator of NK cell-mediated killing in Ovarian Cancer

city: Birmingham

first: Paul

last: Moss

state: West Midlands

address: Vincent Drive

department: Immunology and Immunotherapy

institute: University of Birmingham

summary: Ovarian cancer (OC) is the sixth most common malignancy in women and the poor 5-year survival emphasises the need for novel therapies. NK cells play an important role in the control of malignant disease but the nature of tumour-infiltrating and peripheral NK cells in OC remains unclear. We studied the phenotype and function of NK cells in blood, primary tumour and metastatic tissue in 80 women with OC. The proportion of peripheral NK cells was markedly elevated with a highly activated profile and increased cytotoxicity. In contrast, NK cell numbers in primary tumour and metastasis were substantially reduced, with downregulation of activatory receptors together with elevated PD-1 expression. scRNA-Seq identified 5 NK cell subpopulations along with increased exhausted and immature NK cells within tumour tissue compared to normal tissue. These features were attenuated following chemotherapy where higher levels of activated and cytotoxic NK cells associated with improved disease-free survival. Correlation of NK cell phenotype with clinical outcomes revealed high levels of DNAM-1 expression on tissue-localised and peripheral NK cells to be associated with reduced survival. Expression of PVR, the DNAM-1 ligand, was significantly increased on tumours and DNAM-1 mediated NK cell lysis of primary tumour tissue was observed in vitro. These findings reveal profound modulation of the tumour tissue and systemic profile of NK cells which likely contributes to the high rates of local progression and metastasis seen with OC. Immunotherapeutic approaches that overcome local immune suppression and enhance DNAM-1-targeted lysis of OC offer the potential to improve disease control.

overall_design: Omental tissue samples were taken from 9 women with stage III/IV HGSOC. One of the Omentum tissue samples proved to be a non-metastasis normal sample. All tissue was dissociated and analysed by scRNA-sequencing.

first: Rachel

last: Pounds

first: Wayne

last: Croft

first: Hayden

last: Pearce

first: Tasnia

last: Hossain

first: Kavita

last: Singh

first: Janos

last: Balega

first: David

middle: N

last: Jeevan

first: Sudha

last: Sundar

first: Jason

last: Yap

first: Jianmin

last: Zuo


title: DDO1002, an Nrf2–Keap1 inhibitor, improves impairedhaematopoiesis by reducing ROS production and promoting Nrf2-mediated antioxidative response

city: Hangzhou

first: Aiwei

last: Wu

state: Zhejiang

address: 2318 Yuhangtang Road

department: School of Basic Medical Sciences

institute: Hangzhou Normal University

summary: Oxidative stress reduces haematopoietic stem cell (HSC) function with age, and increased reactive oxygen species (ROS) levels promote DNA damage, cell senescence, and haematopoietic dysfunction. DDO1002, an effective Keap1–Nrf2 inhibitor, may regulate antioxidant gene expression, however, its ability to alleviate impaired haematopoiesis following total body irradiation (TBI) or ageing remains unclear. Through both cellular and mouse models, we showed that DDO1002 upregulated Nrf2, activated the Nrf2-mediated antioxidant response element (ARE) signalling pathway, reduced intracellular ROS levels and delayed cellular senescence. Moreover, DDO1002 reduced DNA damage and HSC apoptosis, thereby increasing the number of HSCs, lymphoid-primed MPP4 cells, and B cells in peripheral blood. Therefore, DDO1002 alleviates TBI-induced haematopoietic injury. Similarly, DDO1002 treatment activated the expression of Nrf2 and Nrf2-mediated ARE signalling pathways in the bone marrow cells of naturally ageing mice. B and T cell proportions in the spleen were increased, as was the colony-forming ability of bone marrow cells. Single-cell sequencing analysis revealed that DDO1002 treatment attenuated intracellular inflammatory signalling pathways and reduced the ROS pathway in aged HSCs, suggesting an ability to restore aged-HSC viability. Thus, DDO1002 effectively activated Nrf2 to delay cell senescence and improved impaired haematopoiesis via the Nrf2–ARE pathway, showing potential for treating age-related haematopoietic disorders.

overall_design: Analysis gene expression and pathways affected by Nrf1-Keap1 inhibitor DDO1002 in each cell populations of bone marrow in single-cell level using scRNA-seq.

first: Yuwen

last: Li

first: Haiping

last: Shen

first: Chenyan

last: Zhao

first: Hu

last: Wang


title: Knockdown of PPARγ can ameliorate benzbromarone-induced obesity-specific drug-induced liver injury

city: Nanjing

first: Sun

last: Peng

address: 101 Longmian Avenue

institute: Nanjing Medical University

summary: Objective: Benzbromarone (BBR) is an effective uric acid-lowering drug. However, it can induce severe liver damage in some patients. Studies have shown that BBR specifically exacerbates hepatic steatosis in obese individuals, leading to aggravated liver injury. The exact mechanism behind this phenomenon remains unclear. Methods: db/db mice were divided into four groups: Control, BBR administration (BBR), Pparg knockdown (Pparg-KD), and BBR administration with Pparg knockdown (BBR + Pparg-KD). One week after AAV8-shRNA-Pparg virus injection, mice were orally administered BBR for four weeks, and changes in blood glucose and body weight were measured. Subsequently, samples were collected, and plasma lipid levels, hepatic lipid content, and liver function parameters were determined. RNA-seq was performed to assess changes in the hepatic gene expression profile and analyze the protective effect of PPARγ knockdown on BBR-induced drug-induced liver injury. Results: Mice in the BBR group exhibited more severe levels of plasma lipids, hepatic lipids, and liver function parameters compared to the Control group. However, mice in the BBR + Pparg-KD group showed significant improvements in these indicators compared to the BBR group. Transcriptomic analysis revealed that BBR administration upregulated the expression of various lipid synthesis-related genes, primarily associated with the PPAR signaling pathway. Furthermore, PPARγ knockdown reversed the increased expression of these lipid synthesis genes. This suggests that PPARγ knockdown has a significant protective effect against BBR-induced drug-induced liver injury. Conclusion: Hepatocyte-specific knockdown of PPARγ can protect against BBR-induced exacerbation of hepatic steatosis and liver injury by inhibiting the promotion of lipid synthesis through PPARγ activation.

overall_design: 4 condition experiments: control, PPAR knockdown, benzbromarone treatment, benzbromarone treatment with PPAR knockdown, biological replicates: 5


title: Different expression of circulating microRNA profile in Tibetan OSAHS with Metabolic Syndrome patients

city: Xining

first: Xuefeng

last: Shi

address: NO2 Gonghe Road，Chengdong District

institute: Qinghai provincial people‘s hospital

summary: To identify distinctive miRNA signatures in OSAHS with Mets patients from healthy subjects, that could serve as diagnostic biomarkers or describe differential molecular mechanisms with potential therapeutic implications. 5 OSAHS with metabolic syndrome (MetS) patients and 4 Tibetan healthy subjects were selected as the control group from January 2018 to January 2021, who signed an informed, written consent form. All OSAHS Patients diagnosed by Polysomnography (PSG). Patients suffering from other respiratory diseases, or combined with allergic and autoimmune diseases, tumors and other serious systemic serious primary diseases were excluded from this study. Plasma was isolated and frozen at -80 ◦C.

overall_design: Four Tibetan healthy subjects and five Tibetan OSAHS patients with MetS were selected for high-throughput sequencing of miRNAs. Total plasma RNA was extracted with Trizol (Tiangen, Beijing) and assessed with Agilent 2100 BioAnalyzer (Agilent Technologies, Santa Clara, CA, USA) and Qubit Fluorometer (Invitrogen). Total RNA per sample was used as input material for the small RNA library. Illumina Hiseq 2500 platform was used to sequence the library preparations and 50bp single-end reads were generated.

first: Xue-feng

first: Xiang

last: He

first: Ze-rui

last: Sun

first: Jie

last: Duo

first: Hao

last: Yang


title: Benzbromarone exacerbates high-fat-induced lipid accumulation in primary hepatocytes by activating PPARγ [OA]

summary: Objective: Benzbromarone (BBR) is an effective uric acid-lowering drug, and studies have shown that BBR can exacerbate hepatic steatosis in obese individuals. However, the underlying mechanisms remain unclear. Methods: Primary hepatocytes isolated from C57/BL6 mice were cultured in vitro, and a high-fat culture model was simulated with 20mM oleic acid (OA) treatment. OA and bovine serum albumin (BSA) were mixed at a ratio of 1:4, pre-treated at 37°C for 1-2 hours, and then co-incubated with primary hepatocytes for 16 hours. The in vitro experiments were divided into four groups: control (BSA), control treatment group (BSA+BBR), high-fat group (OA), and high-fat treatment group (OA+BBR). After 16 hours of treatment, intracellular triglyceride (TAG) content was measured, and Bodipy staining was used to observe the number and morphological changes of lipid droplets. RNA-seq analysis was conducted to assess changes in the gene expression profile of hepatocytes with BBR treatment under BSA and OA conditions. Results: BBR significantly increased the intracellular TAG content in primary hepatocytes treated with OA, while no significant increase was observed in the BSA treatment group. Bodipy staining experiments also confirmed that BBR led to an increase in the number and size of lipid droplets under OA treatment. Transcriptomic data revealed that under both BSA and OA conditions, BBR upregulated the expression of a large number of genes related to lipid synthesis, which were associated with the activation of the PPARγ signaling pathway. Conclusion: BBR promotes the expression of genes involved in lipid synthesis in primary hepatocytes by activating PPARγ, leading to specific hepatic lipid accumulation under high-fat conditions.

overall_design: 4 condition experiments: control, high-fat diet (oleic acid supplementation), benzbromarone treatment group, benzbromarone treatment with high-fat diet (oleic acid supplementation), biological replicates: 3.


title: A novel USP4 inhibitor suppresses colorectal cancer stemness and enhances chemotherapy sensitivity by promoting the degradation of β-catenin and Twist1

city: Luzhou

first: Fengtian

address: Zhongshan Road

institute: Southwest Medical University

summary: The high mortality rate of metastasis colorectal cancer (CRC) is mainly due to chemotherapy resistance. Evidence implicates cancer stem cells (CSCs) play essential roles in chemoresistance. The deubiquitinating enzymes are vital regulators in both CSCs maintenance. Targeting deubiquitinase might be potential strategies to clear CSCs and overcome chemotherapy resistance. Here, we demonstrated that ubiquitin-specific peptidase 4 (USP4) is a key regulator of cancer stemness by stabilizing β-catenin and Twist1 proteins in CRC cells. Additionally, U4-I05, a novel natural small molecule that targets the enzyme activity of USP4 is characterized. U4-I05 binds to the catalytic domain of USP4 at nanomolar concentrations, resulting in the proteasome-mediated degradation of β-catenin and Twist1. Furthermore, U4-I05 attenuated CSC features and augmented sensitivity to oxaliplatin and 5-fluorouracil. In a genetically engineered CRC mouse model, U4-I05 inhibited tumor metastasis and prolonged survival. Overall, this study identifies U4-I05 as a USP4 inhibitor that has meaningful efficacy toward CRC.

overall_design: To investigate the potential deubiquitinase regulating drug resistance in CRC, we collected 8 primary tumor tissues from CRC patients by surgery, including 4 partial response (PR) samples and 4 progression stable (PD) samples after initial neoadjuvant therapy.

first: Chengmei

last: Huang

first: Enen

first: Wenting

last: Liao


title: 3'-seq analysis in control and CFIm25 depleted HeLa cells

city: guangzhou

first: chengguo

last: yao

address: No. 74 zhongshan 2rd road

department: school of medicine

institute: sysu

summary: To understand the polyadenylation site usage at the transcriptome level before and after CFIm25 depletion,  we carried out 3'-seq analysis in control and CFIm25-depleted HeLa cells using 3'-seq kit (Lexogen, 016.24)

overall_design: Two  siRNAs targeting CFIm25 were transfected into HeLa cells for 3 days, total RNAs were harvested and utilized for 3'-seq library preparation. Standard bioinformatics pipeline were used for downstream analysis.

first: Qiuming

last: Feng

first: Zejin

last: Lin

first: Danhui

first: Congting

last: Ye

first: Chengguo

last: Yao