title: Hepatic stellate cells regulate liver fatty acid utilization via plasmalemma vesicle-associated protein

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

Summary: The liver is essential for normal fatty acid utilization during fasting. Circulating fatty acids are taken up by hepatocytes and esterified as triacylglycerols for either oxidative metabolization and ketogenesis or export. Whereas the regulation of fatty acid oxidation in hepatocytes is well understood, the uptake and retention of non-esterified fatty acids by hepatocytes is not. Here, we show that murine hepatic stellate cells (HSCs) and their abundantly expressed plasmalemma vesicle-associated protein (PLVAP) control hepatic substrate preference for fasting energy metabolism. HSC-specific ablation of PLVAP in mice elevated hepatic insulin signaling and improved glucose tolerance. Fasted HSC PLVAP knockout mice showed suppressed hepatic fatty acid esterification to di- and triacylglycerols shifting fasting metabolism from fatty acid oxidation to reliance on carbohydrates. By super-resolution microscopy we localized HSC PLVAP to caveolae residing along the sinusoidal lumen supporting a role for HSCs and PLVAP-diaphragmed caveolae in normal fasting metabolism of the liver.


title: Transcriptomic effects of ERRα repression in human 3D-cultured breast cancer cells.

status: Public on Mar 04 2025

city: LYON

first: Jean-Marc

last: Vanacker

address: 32-34 avenue Tony Garnier

country: France

institute: IGFL, ENS de Lyon, CNRS UMR 5242

type: Expression profiling by high throughput sequencing

summary: Estrogen Related Receptor α (ERRα) is a member of the nuclear receptor superfamily that acts as a transcription factor. In vivo, ERRα exerts diverse physiological functions such as modulation of bone mass and of energy metabolism. In addition, it plays a strong role in cancer progression. Transcriptional targets of ERRα and co-regulators of ERRα transcriptional activity have been identified using two-dimensional (2D) cell culture systems, which only partially reflect the three dimensional (3D) conditions under which a tumor develops. The aim of the study is to determine specific targets of ERRα during cancer progression and to identify new transcriptional co-regulators of ERRα under 3D conditions using a combination of bioinformatics, molecular and cellular biology approaches.

overall_design: MDA-MB-231 cells were cultured in 3D using hanging drop method. They were inactivated for ERRa using two different siRNAs. One control siRNA was used for comparison. In each condition, triplicate samples were analyzed in RNA-seq experiments.

first: Christelle

last: Forcet

first: Violaine

last: Tribollet

first: Catherine

last: Cerutti


title: Hepatic stellate cells regulate liver fatty acid utilization via plasmalemma vesicle-associated protein [bulk RNA-seq]

city: Odense M

first: Daniel

last: Hansen

address: Campusvej 55

country: Denmark

institute: University of Southern Denmark

summary: The liver is essential for normal fatty acid utilization during fasting. Circulating fatty acids are taken up by hepatocytes and esterified as triacylglycerols for either oxidative metabolization and ketogenesis or export. Whereas the regulation of fatty acid oxidation in hepatocytes is well understood, the uptake and retention of non-esterified fatty acids by hepatocytes is not. Here, we show that murine hepatic stellate cells (HSCs) and their abundantly expressed plasmalemma vesicle-associated protein (PLVAP) control hepatic substrate preference for fasting energy metabolism. HSC-specific ablation of PLVAP in mice elevated hepatic insulin signaling and improved glucose tolerance. Fasted HSC PLVAP knockout mice showed suppressed hepatic fatty acid esterification to di- and triacylglycerols shifting fasting metabolism from fatty acid oxidation to reliance on carbohydrates. By super-resolution microscopy we localized HSC PLVAP to caveolae residing along the sinusoidal lumen supporting a role for HSCs and PLVAP-diaphragmed caveolae in normal fasting metabolism of the liver.

overall_design:
Bulk RNA-sequencing from fasted or refed HSC-Plvap-knockout mice, Cav1-knockout mice, and control mice
Bulk RNA-sequencing from over-night fasted HSC-Plvap-knockout and control mice given six weeks of either western diet or high-fat diet

first: Kim

last: Ravnskjaer


title: SOX9 Haploinsufficiency reveals SOX9-Noggin to BMP-SMAD signaling pathway in chondrogenesis

city: Hong Kong

first: See Wing

last: Chan

address: Lo Kwee-Seong Integrated Biomedical Sciences  Building, Area 39, The Chinese University of Hong  Kong

country: Hong Kong

institute: The Chinese University of Hong Kong

summary: SOX9 is well-known for its role in chondrogenesis and gonadogensis. Campomelic Dysplasia (CD) is an example of SOX9 haploinsufficiency-caused rare congenital disease, in which the patients are reported to have skeletal abnormalities. In this study, we created a hiPSC-modeling CD patient and investigated the effect of SOX9 on the regulation of chondrocyte differentiation in BMP-SMAD signaling in vitro. In the CD patient transcriptome, the BMP-SMAD signaling pathway and ribosome-related and chromosome segregation-related gene sets were altered. Upon further experimentation, noggin was found to be significantly upregulated in HT and HM mutants. The overexpression of SOX9 also showed upregulation in SOX9 and COL2A1. . We hope this finding can give a better picture of the dosage-dependent role of SOX9 in chondrogenesis and reveal the manifestation of skeletal dysplasia in CD patients, thereby helping to develop better drugs for these patients.

overall_design: Two SOX9-mutant hiPSC lines, including heterogeneous (HT) and homogeneous (HM) mutations, were generated from a healthy male donor with the mutation designed to mimick medical literature reporting the SOX9 mutation in a CD patient. To investigate the SOX9 dosage effect on cartilage development, hiPSCs were differentiated into chondrocytes and performed transcriptome analysis on Day 14 using the WT (SOX9+/+) and the HT (SOX9+/-) samples.

first: Wai-Yee

first: Tin-Yan

last: Ha

first: See-Wing


title: Genome-wide analysis of RUNX3 binding and histone modification alteration after RUNX3 Knock out

city: Chiba

first: Masaki

last: Fukuyo

address: 1-8-1 Inohana, Chuo-ku

department: Department of Molecular Oncology

country: Japan

institute: Chiba University

type: Genome binding/occupancy profiling by high throughput sequencing

summary: We analyzed histone modification changes at RUNX3 binding sites after RUNX3 knock-pit in HGC27 gastric cancer cell

overall_design: Examination of RUNX3 binding and three different histone modifications in HGC27 wildtype and HGC27 RUNX3 knock out cells.

first: Atsushi

last: Okabe

last: Kaneda


title: RNAseq of WT and Stat6 knockout Tfh21 and Tfh4 cells

city: New Haven

first: Ping-Min

last: Chen

state: CT

address: 333 Cedar Street

department: Immunobiology

country: USA

institute: Yale University

summary: We report that Stat6-driven gene transcription regulates the transition from Tfh21 to Tfh4 cells, suppressing IL-21 production and promoting IL-4 secretion. We identified a cis-enhancer in the second intron of Il21 as a regulator of Tfh cell cytokine transition, via an effect of Stat6 on chromatin accessibility with repression of Il21 transcription. We conclude that Stat6 is necessary for coordinated regulation of IL-21 and IL-4 production by Tfh cells, leading to appropriate maturation of the germinal center B cell response.

overall_design: Examination of 2 different Tfh populations from Stat6 intact and knockout cells.

first: Edward

last: Herman

first: Joe

last: Craft


title: Role of Stat6

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

overall_design: Refer to individual Series


title: Expression difference between stem cell Krt6a+ and differentiated cell WAP+ in mammary precancerous early lesions

city: Houston

first: Chad

last: Creighton

state: TX

address: One Baylor Plaza, Mail Stop: BCM305

department: Biostatistics, Ducan Cancer Center

institute: Baylor College of Medicine

summary: The stem cell hierarchy of normal tissues has been studied extensively for cancer origin, but the stem cell hierarchy of precancerous lesions and its contribution to tumorigenesis remain elusive.  Here, we report that in MMTV-Wnt1 transgenic mice, mammary precancerous lesions harbor both keratin 6a+ precancerous stem cells (pcSC) and more differentiated whey acidic protein (WAP)+ cells. The goal of these data was to understand expression differences between different subsets of cells in mammary precancerous early lesions. There are two cell lines Krt6a+ cells (stem cells) and WAP+ cell (more differentiated cells) from hyperplastic mammary glands in MMTV-Wnt1 mice.

overall_design: Compare the expression between Krt6a+ cells and WAP+ cells.

first: Fengju

first: Yi

last: Li


title: Exosomal miRNA expression profiling in patients with imatinib-resistant chronic myeloid leukemia

status: Public on Mar 03 2025

city: Hat Yai

first: Raphatphorn

last: Navakanitworakul

state: Songkhla

address: Department of Biomedical Sciences and Biomedical Engineering, Faculty Of Medicine, Prince of Songkla University

country: Thailand

institute: Prince of Songkla University

type: Non-coding RNA profiling by high throughput sequencing

summary: Chronic myeloid leukemia (CML) is a stem cell-derived malignancy driven by the BCR-ABL oncogene. Imatinib (IM) is a targeted therapy used to treat CML; however, primary resistance and molecular evidence of persistent disease have been observed in some patients. Recent evidence suggests that exosome-derived microRNAs (miRNAs) contribute to drug resistance and may serve as novel biomarkers for cancer diagnosis and drug sensitivity prediction. This study aimed to explore the plasma exosomal miRNA profiles in patients with CML to identify biomarkers associated with IM resistance. Exosomes isolated from the plasma of patients with IM-sensitive and -resistant CML patients were characterized, and exosomal miRNA profiling was conducted using RNA sequencing. Differential expression analysis identified 13 upregulated miRNAs and 21 downregulated miRNAs. Bioinformatics analysis highlighted pathways related to autophagy and PI3K-Akt signaling. Among the upregulated miRNAs, miR-451 and miR-16 were significantly elevated in exosomes from IM-resistant patients compared with those from IM-sensitive patients. Target gene analysis of these miRNAs was performed. Our findings suggest that plasma exosomal miRNAs, particularly miR-451 and miR-16, can serve as potential biomarkers for IM resistance in CML. These results offer new insights into the molecular mechanisms underlying IM resistance and may inform future therapeutic strategies.

overall_design: case-control study

first: Pirun

last: Saelue

first: Tipparat

last: Penglong

first: Piyatida

last: Molika

first: Natakorn

last: Nokchan

first: Natta

last: Tansila

first: Hansuk

last: Buncherd

first: Supinya

last: Thanapongpichat

first: Kanitta

last: Srinoun


title: Gene expression analysis using RNA-Seq of pustular skin diseases

city: Graz

first: Theresa

last: Benezeder

address: Auenbruggerplatz 8

department: Department of Dermatology and Venereology

country: Austria

institute: Medical University of Graz

summary: The clinical and histopathological features of generalized pustular psoriasis (GPP), a rare but severe neutrophilic condition, overlap with those of acute generalized exanthematous pustulosis (AGEP), making a rapid and reliable distinction difficult. The aim of this study was to elucidate the molecular features of AGEP and GPP in order to identify potential diagnostic biomarkers.

overall_design: Molecular differences of generalized pustular psoriasis (GPP) and acute generalized exanthematous pustulosis (AGEP), compared to palmoplantar pustulosis (PPP), plaque-psoriasis (PSO) and cutaneous adverse drug reactions (ADR) were investigated using RNA-Sequencing of RNA isolated from lesional FFPE skin biopsy samples.

first: Natalie

last: Bordag

first: Peter

last: Wolf


title: Bacterial diacetyl suppresses abiotic stress-induced senescence in Arabidopsis

city: shanghai

first: li

last: peng

country: China

institute: PSC

summary: Plant premature senescence is a major reason for agricultural losses caused by abiotic stress. Tools for suppressing stress-induced plant senescence are important but rare. Herein we report that diacetyl, a natural compound emitted by a plant-beneficial bacterium, suppresses ABA-mediated foliar senescence in Arabidopsis thaliana under various abiotic stress conditions. Our results established diacetyl as an effective protector of stress-induced plant senescence and disclosed a molecular mechanism for bacteria-enhanced plant stress-resistance.

overall_design: Examination of effect of microbial factor in alleviating ABA induced leaf senescence

first: Huiming

last: Zhang

first: Sunil

middle: K

last: Singh

first: Yazhou

last: Sun

first: Yu

last: Yang


title: m6A meRIP-seq of meclofenamic acid treated uveal melanoma cells

city: Shanghai

first: Hao

last: Tian

state: Shanghai

address: No.639, Zhizaoju Road

institute: Shanghai ninth people's hospital, Shanghai Jiaotong University school of medicine

type: Methylation profiling by high throughput sequencing

summary: Uveal melanoma (UM), the most prevalent primary intraocular malignancy in adults with high lethality, is necessitating an urgent need for effective therapeutic interventions. Here we found the meclofenamic acid (MA), an inhibitor of FTO, could be a candidate for UM treatment. To investigate the molecular function of meclofenamic acid (MA), an inhibitor of FTO, MeRIP-seq were performed to map and compare the m6A sites in DMSO and MA treated OMM2.3 cells.

overall_design: We performed m6A meRIP-seq to MA treated vs NC OMM2.3 cells, within 2 samples

first: Hongpei

last: Deng

first: Jing

last: Ruan

first: Xianqun

last: Fan


title: ATAC-seq  in ZFP661 overexpression mESCs

city: Bethesda

first: Jinpu

last: Jin

address: Building 6B, Room 2B-211 6 Center Drive

institute: NIH/NICHD

summary: In this assay, we aimed to investigate the impact of ZFP661 on chromatin accessibility at CTCF barriers.

overall_design: We determined the impact of ZFP661 on ATAC-seq signals at CTCF barriers. ATAC-seq was performed in EV control and ZFP661 overexpression (OE) mESCs, with two biological replicates for each condition.

first: Todd

last: Macfarlan


title: ChIP-seq data for WAPL in ZFP661 overexpression mESCs

summary: In this assay, we aimed to investigate the impact of ZFP661 on WAPL binding at CTCF barriers.

overall_design: We determined the impact of ZFP661 on WAPL binding signals at CTCF barriers. Anti-WAPL ChIP-seq was performed in EV control and ZFP661 overexpression (OE) mESCs, with two biological replicates for each condition.


title: G0S2 modulates normal vitreous-induced proliferation in endothelial cells [1]

city: changsha

first: wenyi

last: wu

state: hunan

address: 87 xiangya road

department: ophthalmology

institute: xiangya hospital central south university

summary: Abnormal blood vessel growth in the eye is a leading cause of vision loss globally, particularly in diseases like diabetic retinopathy where the vitreous plays a crucial but poorly understood role in disease progression. While we know the vitreous can stimulate blood vessel growth, the specific molecular mechanisms remain unclear. Here we show that a protein called G0S2 (G0/G1 switch gene 2) serves as a key regulator of blood vessel growth in response to normal vitreous. Through comprehensive gene analysis, we discovered that G0S2 levels increase significantly when blood vessel cells are exposed to normal vitreous. The importance of G0S2 is highlighted by our finding that uveal melanoma patients with higher G0S2 levels had poorer survival rates. When we removed G0S2 from blood vessel cells, they no longer responded to vitreous stimulation, confirming its critical role. Notably, we identified an existing drug that can target G0S2, potentially offering a new therapeutic approach. This discovery of G0S2's role and its potential therapeutic targeting opens new avenues for treating eye diseases characterized by abnormal blood vessel growth, while also providing a valuable biomarker for predicting disease progression in eye cancer patients

overall_design: RNA-seq techniques to delve into the alterations in transcription and pinpoint a target associated with normal vitreous-treated HUVEC

first: Yiwei

last: Yin

first: Li

last: Pu

first: Xi

first: Ying

last: Zhu

first: Fang

last: Chen

first: Chenkun

last: Wu

first: Hetian

last: Lei

first: Wenyi


title: G0S2 modulates normal vitreous-induced proliferation in endothelial cells [2]

overall_design: RNA-seq techniques to delve into the alterations in transcription and pinpoint a target associated with normal vitreous-treated HREC


title: Beyond the plasma membrane disruption: Novel antifungal mechanism of Neosartorya (Aspergillus) fischeri antifungal protein 2 in Candida albicans

city: Szeged

first: Krisztián

last: Laczi

address: 52. Közép Fasor

department: Biotechnology and Microbiology

country: Hungary

institute: University of Szeged

summary: Candida albicans is the most prevalent human pathogenic fungus, responsible for drug-resistant and fatal invasive infections which show an increasing trend in the past two decades. A promising new therapeutic approach involves NFAP2, an antifungal protein secreted by Neosartorya (Aspergillus) fischeri. NFAP2 exhibits potent antifungal activity on both planktonic and biofilm-forming Candida cells in vitro and in vivo. Despite this promising feature,the exact antifungal mechanism of NFAP2 remains in the shadow which hampers its therapeutic application. Based on our recent observations, we suppose that NFAP2 is taken up by Candida cells, and has a long-term growth-slowing effect. Our objective was to understand the molecular mechanism of the long-term growth slowing effect of NFAP2 in C. albicans, therefore the transcriptome of the NFAP2-treated (below the minimum inhibitory concentration) C. albicans SC5314 cultures was compared to that of the untreated ones.The transcriptional responses to NFAP2 were further characterized using functional enrichment analyses of Gene Ontology terms and Kyoto Encyclopedia of Genes and Genomes pathways.

overall_design: RNA-seq comparison of C. albicans SC5314 cells with NFAP2 treated C. albicans SC5314 cells

first: Kinga

last: Dán

first: Nóra

last: Zsindely

first: László

last: Bodai

last: Galgóczy


title: Expression data from rice young panicles before stage 5 (201817675)

city: Guangzhou

first: Shaoyan

last: Zheng

address: Wushan Road No. 483

institute: South China Agricultural University

summary:
We performed microarray analysis of WT and ago2-1 spikelets tissue before stage 5 to identify target genes
We used microarrays to detail the global gene expression in tissues from normal rice young panicles .

overall_design: Tissues from normal rice young panicles were for RNA extraction and hybridization on Affymetrix microarrays.

first: Jing

last: Li


title: Pumilio regulates synaptic protein function in a 3’ UTR-dependent manner

city: Freiburg

first: Valérie

last: Hilgers

address: Stübeweg 51

country: Germany

institute: MPI of Immunobiology and Epigenetics

summary: The regulation of RNA is crucial for spatiotemporal control of gene expression in neurons, but how the correct localization, levels, and function of synaptic proteins are achieved is not well understood. In this study, we globally investigate the role of alternative 3'UTRs in regulating RNA localization in the synaptic regions of the Drosophila brain. We identify direct mRNA targets of the translational repressor Pumilio, finding that mRNAs bound by Pumilio encode proteins enriched in synaptosomes. Pumilio differentially binds to RNA isoforms of the same gene, where shorter 3'UTRs tend to localize to the synapse, and longer 3'UTRs remain in the neuronal soma. Disruptions in 3'UTR isoform localization and axon outgrowth occur in pumilio mutant neurons. Our results reveal a mechanism of isoform-dependent protein function, demonstrating how neurons can achieve high protein complexity with a restricted set of genes.

overall_design: This study assesses 3' mRNA-sequencing and proteomic raw data of D. melanogaster "Synaptosome" fractions, in addition to Pumilio 3'xRIPseq data of D. melanogaster head isolates, to assess the role of Pumilio in the localization of mRNAs, and translation of Pumilio asociated proteins at the synapse. Input controls samples were obtained for all three data sources.

first: Dominika

last: Grzejda

first: Anton

last: Hess

first: Andrew

last: Rezansoff

first: Sakshi

last: Gorey

first: Judit

last: Carrasco

first: Carlos

last: Alfonso-Gonzalez

first: Stylianos

last: Tsagkris

first: Lena

last: Neuhaus

first: Mengjin

last: Shi

first: Hasan Can

last: Ozbulut

first: Friederike-Nora

last: Vögtle

first: Andreas

last: Vlachos


title: Pumilio regulates synaptic protein function in a 3’ UTR-dependent manner[primary_neuron_RNASeq]

overall_design: This study assesses 3' mRNA-sequencing and proteomic raw data of D. melanogaster "Synaptosome" fractions, in addition to Pumilio 3'xRIPseq data of D. melanogaster head isolates and total RNA-seq raw data of primary D. melanogaster neuron culture, to assess the role of Pumilio in the localization of mRNAs, and translation of Pumilio asociated proteins at the synapse.


title: ATACseq of WT and Stat6 knockout Tfh21, Tfh214, and Tfh4 cells

first: Ping-Min

last: Chen

overall_design: Examination of 3 different Tfh populations from Stat6 intact and knockout cells.

first: Edward

last: Herman

first: Joe

last: Craft


title: ATACseq of Naïve CD4+ cells from WT, Stat6, and Il21e KO mice

summary: We report that Stat6-driven gene transcription regulates the transition from Tfh21 to Tfh4 cells, suppressing IL-21 production and promoting IL-4 secretion. We identified a cis-enhancer in the second intron of Il21 as a regulator of Tfh cell cytokine transition, via an effect of Stat6 on chromatin accessibility with repression of Il21 transcription. Chromatin accessibitiy of this second intron region was not affected in the naive CD4+ T cell population

overall_design: Examination of naïve CD4+ T cells  populations from WT, Stat6, and Il21e KO mice


title: Bacterial immunotherapy leveraging IL-10R hysteresis for both phagocytosis evasion and tumor immunity revitalization [RNA-Seq]

city: shenzhen

first: zhiguang

last: chang

address: No. 1068, Xueyuan Avenue, Shenzhen University Town, Xili, Nanshan District

department: Shenzhen Institute of Synthetic Biology, Shenzhen Institutes of Advanced Technology

institute: Chinese Academy of Sciences

summary: Bacterial immunotherapy holds promising cancer-fighting potential. However, unlocking its power requires a mechanistic understanding of how bacteria both evade antimicrobial immune defenses and stimulate antitumor immune responses within the tumor microenvironment (TME). Here, by harnessing an engineered Salmonella enterica strain with this dual proficiency, we unveiled a singular mechanism underlying. Specifically, the hysteretic nonlinearity of interleukin-10 receptor (IL-10R) expression drives tumor-infiltrated immune cells into a tumor-specific IL-10Rhi state. Bacteria leverage this to enhance tumor-associated macrophages producing IL-10, evade phagocytosis by tumor-associated neutrophils, and coincidently expand and stimulate the preexisting exhausted tumor-resident CD8+ T cells. This effective combination eliminated tumors, prevented recurrence, and inhibited metastasis across multiple tumor types. Analysis of human samples suggested that IL-10Rhi state might be a ubiquitous trait across human tumor types. Our study unveils the unsolved mechanism behind bacterial immunotherapy's dual challenge in solid tumors and provides a framework for intratumor immunomodulation.

overall_design: Jurkat T cells were divided into four groups: Pre-exposure (direct sample collection), Initial exposure (stimulated with 10 ng/ml IL-10 for 6 h), Rest (stimulated with 10 ng/ml IL-10 for 6 h, washed, and cultured for 48 h in 0.5 ng/ml IL-10 with medium changes every 12 h), and Subsequent exposure (same as Rest, with an additional 6-h stimulation with 10 ng/ml IL-10)

first: Zhiguang

last: Chang

first: Xuan

last: Guo

first: Xuefei

last: Li

first: Yan

last: Wang

first: Zhongsheng

last: Zang

first: Yichuan

last: Xiao

first: Chenli

last: Liu


title: Stat-6 signaling pathway and not Interleukin-1 mediates multi-walled carbon nanotube-induced lung fibrosis in mice: insights from an adverse outcome pathway framework [IL1-R1_KO]

city: Ottawa

first: Sabina

last: Halappanavar

state: Ottawa

address: 251 Sir Frederick Banting Dr.

country: Canada

institute: Health Canada

summary: Five-to-seven week old female wild type C57BL/6 mice (WT) and C57BL/6 mice deficient in IL1-R1 (IL1-R1 KO) were exposed to  Mitsui-7, a type of multiwalled nanotube at a dose of 162 µg/mouse by intratracheal administration. Inflammation was assessed 24 h and 28 days following treatment and fibrotic leison was assessed 28 days following treatment. Inflammation was lower in IL1-RI KO mice compared to that observed in the wild type mice at 24h post exposure. This diffrence was no longer observed at 28 days post-exposure. In contrast, STAT6 KO mice showed suppressed inflammation and fibrotic leison at 28 days post-exposure compared to the wild type mice. The results from this study suggest that STAT 6 signaling pathway is essential for multiwalled nanotube induced fibrotic desease.

overall_design: Wild type (WT) C57BL/6 and IL1-R1 KO mice were exposed to Mitsui-7 (multiwalled carbon nanotubes (MWCNT)) at a dose of 162 µg/mouse by intratracheal administration in a 50 µl suspension   Tissues were collected 1 and 28 days post-instillation.

first: Jake

last: Nikota

first: Laura

middle: R

last: Goodwin

first: Dongmei

last: Wu

first: Andrew

last: Williams

first: Carole

middle: L

last: Yauk

first: Håkan

last: Wallin

first: Ulla

last: Vogel


title: Stat-6 signaling pathway and not Interleukin-1 mediates multi-walled carbon nanotube-induced lung fibrosis in mice: insights from an adverse outcome pathway framework [STAT6_KO]

summary: Five-to-seven week old female wild type C57BL/6 mice (WT) and C57BL/6 mice deficient in STAT6 (STAT6 KO) were exposed to  Mitsui-7, a type of multiwalled nanotube at a dose of 162 µg/mouse by intratracheal administration. Inflammation was assessed 24 h and 28 days following treatment and fibrotic leison was assessed 28 days following treatment. Inflammation was lower in IL1-RI KO mice compared to that observed in the wild type mice at 24h post exposure. This diffrence was no longer observed at 28 days post-exposure. In contrast, STAT6 KO mice showed suppressed inflammation and fibrotic leison at 28 days post-exposure compared to the wild type mice. The results from this study suggest that STAT 6 signaling pathway is essential for inducing  fibrotic desease by multiwalled nanotube.

overall_design: Wild type (WT) C57BL/6 and STAT6 KO mice were exposed to Mitsui-7 (multiwalled carbon nanotubes (MWCNT)) at a dose of 162 µg/mouse by intratracheal administration in a 50 µl suspension   Tissues were collected 1 and 28 days post-instillation.


title: Macrophage-KLF6 signaling promotes experimental atherogenesis

city: Cleveland

first: Ernest

last: Chan

state: OH

address: 10900 Euclid Ave, Robbins E211

department: PQHS

institute: CWRU

summary: Cardiovascular disease accounts for one in every four deaths in the United States and is the single largest cause of mortality around the world.  The most common cause of cardiovascular-related deaths are due to development of occlusive atherosclerotic plaques. A hallmark event in the development of atherosclerotic plaque is the accumulation of lipid-laden macrophages in the subendothelial layers of affected blood vessels.  Macrophages are key players in all stages of atherogenesis, including plaque initiation, growth, rupture, as well as healing of ruptured plaques. In this context, macrophages are the principal innate immune cells that modulate atherogenesis by engaging in various processes such as inflammation, extracellular matrix degradation, phagocytosis, and efferocytosis. Here, we report that macrophage Kruppel-like factor 6 (KLF6) deficiency attenuates pro-inflammatory gene expression and experimentally induced atherosclerotic plaque development. Our in vivo studies show that myeloid-KLF6 deficiency on Apoe-null background significantly curtails high-fat/high-cholesterol diet-induced atherosclerotic lesion formation and macrophage abundance in atherosclerotic plaques.  Integrated transcriptomics and Gene Set Enrichment Analysis show that KLF6 deficiency significantly attenuates a large number of TNF-induced gene targets, and TNF-induced IFN response, IFN response, and inflammatory response signaling in macrophages. At the molecular level, KLF6 promotes IRF1 signaling to enhance TNF-induced pro-inflammatory gene expression in macrophages. Collectively, our analyses show that KLF6 promotes pro-inflammatory gene expression in macrophages and boosts experimentally induced atherosclerotic plaque formation in vivo.

overall_design: Lyz2cre and Klf6fl/fl:Lyz2cre mice BMDMs were stimulated with 10ng/ml TNF for 6 hours. Total RNA samples were subjected to RNAseq analyses.

first: Ganapati

middle: H

last: Mahabeleshwar


title: Noncanonical role of NCOR1 as a facilitator of DNA mismatch repair and its deficiency sensitizes cancers to immune checkpoint blockade therapy [scRNA-seq]

city: Beijing

first: Xuejiao

last: Ren

address: Beijing

institute: Nanjing Medical university

summary: Tumor genomic heterogeneity significantly influences the efficacy of immune checkpoint blockade (ICB) therapy. To elucidate the underlying mechanisms, we pioneered the development of an ICB response score (IRS) based on machine learning analysis of microenvironmental features. Through a pan-cancer genomic screening, we identified the nuclear receptor corepressor NCOR1 as a key regulator, the tumors with genomic deficiency of which display a tumor infiltrating lymphocyte (TIL)-inflamed microenvironment. Genetic ablation of Ncor1 delays the tumorigenesis and metastasis in syngeneic and spontaneous tumor models in immunocompetent mice. Mechanistically, NCOR1 guards DNA mismatch repair by directly interacting with MSH2 and recruiting MutSa to chromatin for mismatch recognition, independent of its transcriptional regulatory activity coupling with histone deacetylase. Ncor1 depletion in hepatocellular carcinoma and melanoma cells promotes tumor immunogenicity by increasing tumor mutation burden (TMB), neoantigen load, and TIL infiltration and activation, thereby enhancing anti-PD-1 therapy efficacy. Our findings reveal that NCOR1 loss represents a novel mechanism underlying TMB-high tumors with intact MMR components, broadening the application of ICB.

overall_design: Subcutaneous xenografts derived from Hepa1-6 and B16 cells were generated in immunocompetent C57BL/6J mice. Subcutaneous xenografts were dissociated and the single-cell suspensions were obtained using the MACS Miltenyi Mouse Tumor Dissociation kit (130-096-730, Miltenyi Biotec, Germany) on gentleMACs dissociator with Octo Heaters (130-096-427, Miltenyi Biotec, Germany) according to manufacturer’s instructions. Cell suspensions were passed through a 70-µm filter twice. CD45+ immune cells were then sorted from the cell suspension using flow cytometry (Cat# 35-0451-U100, TONBO Biosciences, USA), and then subjected to the BD Rhapsody Single-Cell Analysis System (BD Biosciences, USA) following the manufacturer’s guidelines. The scRNA-seq libraries were constructed using BD Rhapsody WTA Amplification Kit (BD Biosciences, USA). WTA libraries and LMO libraries were pooled and sequenced on NovaSeq 6000 (Illumina, USA), and the data was processed using the BD Rhapsody WTA analysis pipeline (v1.9.1; BD Biosciences, USA). WTA reads were aligned to the mm10 reference mouse genome, allowing a maximum of 1 mismatch. All samples were merged in Seurat and high-quality cells were kept with a detection threshold of 500 - 5,000 genes and a proportion of expressed mitochondrial genes less than 10%. After quality control, a total of 9,693 cells from 3 groups of HCC samples (sgCtrl, sgNcor1-1 and sgNcor1-2), and 4,910 cells from 3 groups of melanoma samples (sgCtrl, sgNcor1-1 and sgNcor1-2) were retained for downstream analyses. Data of different samples were integrated utilizing Harmony (Korsunsky et al., 2019) to identify anchors. Then, data were log-normalized (divided by the total expression and amplified scaling factor 10,000) using the “NormalizeData” function in Seurat. For clustering, we implemented the “FindVariableFeatures” function in Seurat to select the top 2,000 highly variable genes (HVGs). A principal component analysis (PCA) matrix was calculated to reduce noise using the “RunPCA” function in Seurat with default parameters. For visualization, the dimensionality was further reduced using “RunUMAP” function in the Seurat with parameters n.neighbors = 50, min.dist = 0.1, spread = 1, and metric = euclidean. We then used the function “FindClusters” with resolution = 1.0 to perform the first-round clustering and annotated each cluster by known cell type markers.

first: Gangqiao

last: Zhou


title: RNA-seq and Ribo-seq of PHYHD1-WT,PHYHD1△107-130（MT） and EV ccRCC cell line（7860）

first: Dengfeng

last: Huang

address: 301 Yanchang Middle Road

institute: Shanghai Tenth People's Hospital

summary: We used RNA seq and Ribo-seq to evaluate the PHYHD1 gene expression changes among different groups (EV, MT, WT) to investigate the potential mechanisms by which PHYHD1 exerts its negative regulatory role in inhibiting excessive protein synthesis.

overall_design: The 7860 ccRCC kidney cancer cell lines, carrying empty vector, overexpressing PHYHD1 (MT), and the untreated wild-type group, were cultured in vitro in three separate 10 cm dishes for each condition, and the samples were subsequently collected for experiments.

first: Qian

last: Liang


title: Angiogenesis blockade overcomes acquired KRAS G12D inhibitor resistance driven by KRAS-PI3Kγ interaction [scRNA-Seq]

city: Seongnam

first: Ji-Won

last: Kim

state: Gyeonggi-do

address: 82 Gumi-ro-173-beon-gil

department: Internal Medicine

country: South Korea

institute: Seoul National University Bundang Hospital

summary: The KRAS G12D mutation is a key oncogenic driver in many solid tumors, including pancreatic, gastric, and colorectal cancers. While recent preclinical studies have characterized features associated with innate and acquired KRAS G12D inhibitor resistance, strategies to overcome resistance, especially in the gastrointestinal cancer context, remain underexplored. Here, we generated nine gastrointestinal cancer models of acquired resistance to the KRAS G12D-selective inhibitor MRTX1133. We identified the enrichment of angiogenesis, hypoxia, and epithelial-to-mesenchymal transition (EMT) in an isogenic patient-derived organoid model of acquired resistance by single-cell RNA sequencing. In the nine resistant models, VEGFA expression and VEGFR2 phosphorylation were unanimously increased. Subsequent mechanistic studies revealed that an autocrine VEGFA signaling loop, initiated by an increased interaction between KRAS and PI3Kγ, drives both EMT and RAS independence. Elevated mitochondrial oxidative stress in resistant cells led to CCT2-mediated KRAS stabilization, thereby enhancing PI3Kγ activity. Moreover, we observed that cancer-vascular paracrine signaling both amplified angiogenesis and EMT signatures in cancer cells and promoted endothelial cell proliferation. Significantly, disruption of VEGFA signaling reversed EMT induction and restored sensitivity to MRTX1133. Concordantly, in mouse xenograft models, the combination of anti-VEGFR2 therapy and MRTX1133 rechallenge significantly reduced tumor growth, angiogenesis, and proliferation markers without adverse effects on body weight. These findings identify a critical role for VEGFA signaling in resistance to KRAS G12D inhibition and provide a rationale for combination therapies targeting angiogenesis in gastrointestinal cancers.

overall_design: scRNA-seq of normal, patental, and resistant organoids

first: Sung-Hyun

last: Hwang

first: Mingyun

last: Bae


title: DNA methylation dynamics in the prenatal and postnatal human cortex

city: Exeter

first: Alice

last: Franklin

address: Stocker Road

country: United Kingdom

institute: University of Exeter

summary: There is increasing recognition about the importance of epigenetic dysregulation in neurodevelopmental disorders including autism spectrum disorder and schizophrenia, yet little is known about patterns of gene regulation in the later stages of fetal development and the first decade of life. In this study we profiled changes in DNA methylation, an epigenetic modification to cytosine involved in mediating the developmental regulation of gene expression and function, across human brain development in cortex tissue from 107 human fetal and child donors spanning 6 post-conceptual weeks to 8 years old.

overall_design: DNA methylation of post-mortem bulk pre-frontal cortex tissue was profiled for 107 individuals: 95 fetal (6 - 33 post-conceptual weeks) and 12 child (0 - 8 years).

first: Jonathan

last: Mill

first: Emma

last: Dempster

middle: M

last: Walker


title: Cell-type-specific DNA methylation dynamics in the prenatal and postnatal human cortex

summary: There is increasing recognition about the importance of epigenetic dysregulation in neurodevelopmental disorders including autism spectrum disorder and schizophrenia, although the cell-type specific changes in gene regulation across critical periods of brain development have not been fully elucidated. In this study we profiled DNA methylation of purified populations of neuronal (SATB2+) and non-neuronal (SATB2-) cell-types in 47 human fetal and child donors (8 post-conceptual weeks to 8 years old).

overall_design: Post-mortem pre-frontal cortex tissue was collected for 47 individuals: 38 fetal (8 - 28 post-conceptual weeks) and 9 child (0 - 8 years). Using a FANS protocol developed by our group (Davies et al. 2023), individual nuclei fractions (SATB2+, SATB2-) were isolated and DNA methylation profiled.


title: RBM39 promotes hepatocarcinogenesis by regulating RFX1's alternative splicing and subsequent activation of integrin signaling pathway

city: Chengdu

first: Bo

last: Zhang

state: Sichuan

institute: West China Hospital,SCU

summary: There is increasing evidence that alternative splicing (AS) is crucial for tumor cells because it can produce various protein isoforms that may play different or even opposing roles in tumor growth and metastasis. Despite its significance, the role of AS and related splicing factors, particularly splicing-related messenger ribonucleoproteins (mRNPs), in hepatocarcinogenesis is poorly understood. High-throughput transcriptome sequencing of HCC patients revealed that the spliceosome pathway may play an important role in HCC development. Through the combined analysis of the three gene clusters consisting of differentially expressed genes (DEGs), genes encoding RNA-binding proteins (RBPs) and genes related to splicing-related mRNPs, the splicing factor RBM39 was identified, which was highly expressed in HCC tumor tissues with prognostic value. Functional studies showed that RBM39 silencing inhibited cell proliferation, migration and invasion via the integrin pathway. By performing RNA immunoprecipitation sequencing (RIP-seq), we found that RBM39 combined with RFX1 pre-mRNA and regulated alternative splicing of its exon 2. Mechanistically, the skipping of exon 2 in RFX1, influenced by high RBM39 expression in HCC cells, led to production of an N-terminal truncated RFX1, which lost the ability to transcriptionally repress oncogenic collagen genes. This process further activated the downstream FAK/PI3K/AKT signaling pathway. Furthermore, we further validated these findings in the hydrodynamic tail vein injection (HTVI) mouse model and human HCC tissues. Therefore, we hypothesized that high RBM39 expression enhances the malignant capabilities of HCC cells by regulating the alternative splicing of RFX1 and subsequently activating the FAK/PI3K/AKT signaling pathway.

overall_design: To investigate the function of RBM39 in hepatocellular carcinoma, we established Huh7 cell lines in which each target gene has been knocked by shRNA;To verify the transcriptomic differences between liver cancer tissues and their adjacent tissues, we examined 5 pairs of liver cancer and adjacent tissues using RNA-Seq.

first: Yongjie

first: Jiayin

last: Yang


title: Biosensor-guided evolution boosts itaconic acid production, unveiling novel insights on the stringent response

city: Ulsan

first: Donghyuk

address: 50 UNIST-gil, Eonyang-eup, Ulju-gun

department: Department of Chemical Engineering

institute: UNIST

summary: Acetate is a cost-effective and sustainable carbon source that, despite its potential, remains underutilized. This study employed biosensor-assisted adaptive laboratory evolution (ALE) to enhance itaconic acid production and acetate metabolism in Escherichia coli. The evolved E. coli W strains exhibited 65% increase in itaconic acid production and 71% increase in growth rate, and 45% increase in itaconic acid yield. A common 31-kb genomic deletion was identified in the evolved strains, with two genes, ecw_m2276 and ecw_m2277, driving the observed phenotypic changes. The evolved strains exhibited an intensified stringent response, which enhanced the acetate-utilizing pathway and resulted in over a 5,000% increase in the expression of the glyoxylate shunt, thereby boosting microbial growth. Overexpression of relA further replicated these enhanced phenotypes. Our findings highlight not only significant physiological improvements but also present a novel strategy for enhancing microbial growth and bioproduction from acetate, offering valuable insights for industrial biotechnology applications.

overall_design: A total of 36 samples were analyzed. Itaconate producing E. coli W parental (WCS0) and ALE strains (WCS6, WCS19, and WCS23) were cultured on modified M9 acetate medium and sampled at three timepoints with biological triplicates. mRNA reads were utilized for analysis.

first: Jihoon

last: Woo

first: Joon-Young

last: Park


title: Bacterial immunotherapy leveraging IL-10R hysteresis for both phagocytosis evasion and tumor immunity revitalization [ATAC-seq]

first: zhiguang

last: chang

first: Zhiguang

last: Chang

first: Xuan

last: Guo

first: Xuefei

last: Li

first: Yan

last: Wang

first: Zhongsheng

last: Zang

first: Yichuan

last: Xiao

first: Chenli

last: Liu


title: Bacterial immunotherapy leveraging IL-10R hysteresis for both phagocytosis evasion and tumor immunity revitalization [CUT&Tag]

overall_design: Workflow for isolating and treating primary CD8 T cells from mouse spleens. Briefly, isolated CD8+ T cells were stimulated with anti-mouse CD3ε and CD28 antibodies for 12 h, followed by antibody removal and washing. Cells were divided into four groups: Pre-exposure (direct sample collection), Initial exposure (stimulated with 10 ng/ml IL-10 for 6 h), Rest (stimulated with 10 ng/ml IL-10 for 6 h, washed, and cultured for 48 h in 0.5 ng/ml IL-10 with medium changes every 12 h), and Subsequent exposure (same as Rest, with an additional 6-h stimulation with 10 ng/ml IL-10)


title: Bacterial immunotherapy leveraging IL-10R hysteresis for both phagocytosis evasion and tumor immunity revitalization [ATACseq]


title: Bacterial immunotherapy leveraging IL-10R hysteresis for both phagocytosis evasion and tumor immunity revitalization [CUT&Tag 2]


title: Depletion of Apc gene in Cdx2 Gastro ntestinal Cells Facilitates Metastasis of Colorectal Adenocarcinoma Lgr5 Cells to Distant Organs

first: Ernest

last: Chan

summary: Caudal type homeobox 2 (CDX2) is a transcription factor expressed in the gastrointestinal (GI) epithelial (IEC)   and stromal cells .CDX2 along with APC can regulate Lgr5 intestinal stem cell (ISC) differentiation to control GI   tract development or intestinal neoplasia. CDX2 or APC loss function is associated with colorectal cancer (CRC) advance. However, whether APC directly regulates CRC metastasis is not clear. We aim to determine the role of inactive Apc gene in Cdx2 GI cells on Lgr5 ISC metastasis.

overall_design: We performed gene expression profiling analysis using the date of rectal tissue from Lgr5CreER;APC flox mice,CDX2creER;APC flox mice and Lgr5CreER;CDX2creER;APC flox mice

first: Xiaonan

last: Han

first: Ahmed

last: Bakheet

first: Wen

last: Gao

first: E


title: Early transcriptomic responses of susceptible and resistant (Ma gene -containing) Prunus cerasifera accessions to the root knot nematode Meloidogyne incognita

city: Sophia Antipolis

first: cyril

last: van ghelder

address: 400 route des Chappes

institute: INRAE

summary: Root-knot nematodes (RKNs), Meloidogyne spp., severely challenge plants worldwide and especially perennials. In Prunus spp., the genetic resistance to RKNs mainly relies on NLR (NB-LRR) genes that are key factors for pathogens control. In Prunus cerasifera, the Ma gene, cloned in 2011, is characterized by a complete-spectrum and heat-stable resistance that has not been overcome under field and controlled conditions up-to-now. This resistance occurs relatively early in the interaction process as RKN penetrate the roots but never succeed in inducing their feeding site and die in the root. Besides its rare ability, the Ma gene has a peculiar TNL structure comprised of five repeated post-LRR domains (a.k.a. C-JID), which is unique among plants. Conversely to other TNL in model plants, no transcriptional analyses related to this gene have been performed so far.   In this study, we explore the early transcriptional response that occurs in both, susceptible (no Ma gene) and resistant (Ma-containing) Prunus cerasifera accessions facing a strong inoculum pressure of Meloidogyne incognita, the model species for RKN. Our RNAseq approach allows us to better understand the transcriptional response of a woody perennial in both the compatible and incompatible interactions with RKN, thus paving the way for future functional studies.

overall_design: 3 biological replicates were analyzed for each of 4 conditions (2 genotypes; 2 treatments per genotype)

first: Cyril

last: Van Ghelder


title: Adaptive variation in mutagenesis driven by protein self-assembly

city: Stanford

first: Christopher

last: Jakobson

state: CA

address: 318 Campus Dr, Clark Center W350

department: Chemical and Systems Biology

institute: Stanford University School of Medicine

summary: Mutations supply raw material for evolution.  However, most are not adaptive. Thus, shifts in mutagenesis are typically transient. Nonetheless, modelling predicts that a heritable but revertible ‘mutagenesis switch’ would win in many selective landscapes. Here we report that prions formed by DNA repair proteins endow Saccharomyces cerevisiae with this capacity, sparking heritable variation in mutagenesis rates in evolving populations from the laboratory, nature, and the clinic. Self-templating transforms the functions and interactions of these DNA fidelity factors, enabling resilience to genotoxic stress and the emergence of drug resistance. In the fungal pathogen C. albicans, which diverged from S. cerevisiae ~300 million years ago, factors supporting prion inheritance promote the evolution of resistance to fluconazole, a mainline antifungal. Our findings suggest that protein self-assembly, a collective molecular behavior that is common among DNA replication and repair factors, can materialize epigenetic memory that tunes the balance of genome diversification and fidelity to expand adaptive opportunities.

overall_design: To understand the effects of yeast prions on gene expression, we measured mRNA levels in a variety [PRION+] strains alongside naive and cured controls.

first: Alexandria

last: Van Elgort

first: James

last: Byers

first: Raymond

last: Futia

first: Yiwen

last: Chen

first: Thomas

last: Lozanoski

first: Zachary

last: Harvey

first: David

last: Garcia

first: Daniel

last: Jarosz


title: Comparative Transcriptome of cattle PBMCs post Mycobacterium tuberculosis infection

city: Hyderabad

first: Bappaditya

last: Dey

state: Telangana

address: Survey No. 37, Extended Q City Road, Gachibowli

country: India

institute: National Institute of Animal Biotechnology

summary: This comparative transcriptomic study examines the differences in the gene expression profile in PBMCs from indigenous Sahiwal and Crossbred (Sahiwal x Holstein Friesian) cattle in response to Infection with virulent Mycobacterium tuberculosis and vaccine stain M. bovis BCG.

overall_design: Peripheral blood mononuclear cells (PBMCs) were collecetd from healthy and tuberculosis negative Sahiwal (Indigenous) and Sahiwal x Holstein Friesian (Crossbred) cattle. PBMCs were infected with M. bovis BCG and M. tuberculosis H37Rv strains, and uninfected PBMCs served as controls. Total RNA was extracted from unstimulated and infected PBMCs and subjected to RNA requencing on the Illumina (NovaSeq 6000) platform.

first: Rishi

last: Kumar

first: Sripratyusha

last: Gandham

first: Hemanta

last: Maity

first: Uttam

last: Sarkar


title: RBM39 promotes hepatocarcinogenesis by regulating RFX1's alternative splicing and subsequent activation of integrin signaling pathway [RIP-seq]

first: Bo

last: Zhang

overall_design: To investigate the mRNA binding with RBM39 in hepatocellular carcinoma, we established Huh7 cell lines with or without kockdown RBM39.RIP were peformed in both Huh7 cell lines.

first: Yongjie

last: Zhou

first: Jiayin

last: Yang


title: CCL3-Mediated Inflammatory Reprogramming of the Hepatocellular Carcinoma Microenvironment Enhances Macrophage Antigen Presentation and Adaptive Immune Response (RNA-Seq)

first: Muqi

last: Liu

state: Hunan

address: No.138 Tongzipo Road, Yuelu District, Changsha

department: Institute for Cell Transplantation and Gene Therapy

institute: the 3rd Xiangya Hospital of Central South University

summary: Hepatocellular carcinoma (HCC) is a major cause of cancer-related mortality worldwide, largely due to its complex and immunosuppressive tumor immune microenvironment (TIME), which significantly impairs the efficacy of conventional therapies and immune checkpoint blockade (ICB). This study investigates the role of C-C motif chemokine ligand 3 (CCL3) in modulating the HCC TIME, focusing on its impact on immune cell recruitment, macrophage-mediated antigen presentation, and the overall antitumor immune response. We analyzed CCL3 expression in human HCC samples and examined its correlation with inflammatory gene signatures and immune cell infiltration. Using high-dimensional single-cell RNA sequencing (scRNA-seq), multiparameter flow cytometry, and multiplex immunofluorescence, we elucidated how CCL3 influences macrophage functionality and T cell activation. In preclinical HCC models and ex vivo tumor fragment assays, we explored the mechanisms by which CCL3 affects macrophage function and its broader implications for antitumor immunity. Our findings reveal that CCL3 effectively recruits immune cells to the HCC TIME, promotes the formation of tertiary lymphoid structures, and enhances macrophage-mediated antigen phagocytosis and presentation, leading to improved T cell effector functions and cytotoxic activity. This research underscores the critical role of CCL3 in reshaping the HCC TIME to enhance antitumor immunity and suggests that targeting CCL3 could be a promising strategy to improve the efficacy of immunotherapy in liver cancer.

overall_design: Cultivate and isolate macrophages from the bone marrow of C57BL/6J mice using recombinant protein CCL3. After seven days of isolation and culture, mature the macrophages and add recombinant protein CCL3 for 3 days of culture for transcriptome sequencing

first: Xiaoqian

last: Ma

first: Wei

last: Wang


title: Billion-Scale production of functional hiPSC-derived cardiomyocytes in bioreactors through oxygen control and Wnt Activation

city: Pamplona

first: Asier

last: Ullate-Agote

state: Navarra

address: Av. de Pío XII, 55

department: Hemato-Oncology

country: Spain

institute: CIMA

summary: Producing therapeutic quantities of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM) for myocardial infarction treatment remains a significant challenge. We demonstrate that precise control of dissolved oxygen (DO) at low levels combined with Wnt pathway activation, through continuous perfusion of CHIR99021, enables the production of billions of functional hiPSC-CM in stirred-tank bioreactors (STB). Specifically, culturing hiPSC-CM aggregates under 10%O2 led to an upregulation of pathways involved in cell proliferation and survival, resulting in a significantly higher hiPSC-CM expansion factor  when compared to hiPSC-CM under atmospheric normoxia and static culture systems. Scaling up the process to a 2L STB, while maintaining constant power input per volume, generated 4 billion highly pure hiPSC-CM, with more than 90% positive-cells for cardiac markers. hiPSC-CM aggregates also showed spontaneous beating, expression of cardiac markers and were able to further mature in culture, revealing improved gene expression, sarcomere alignment and cardiac action potential.

overall_design: Bulk RNA-seq of cardiomyocytes produced in different conditions both in bioreactor (normoxia, hypoxia) and in T-flasks, as well as two weeks of maturation after bioreactor production under hypoxia

first: Margarida

last: Serra

first: Pedro

last: Vicente


title: Identifying targets of the zinc finger transcription factor Salm during Drosophila myogenesis

city: SAINT LOUIS

first: Dongkook

last: Park

state: Missouri

address: 660 S. Euclid Avenue Campus Box 8103

department: Developmental Biology

institute: Washington University in St.Louis

summary: We performed a forward genetic screening and identifid the transcription factor, salm. To identify potential downstream targets, we sorted the developing muscle cells from stage 11 embryo using GFP tagged by TEY-gal4 in wild type vs salm[340] mutants. This approach successfully identified the potential SALM-target genes.

overall_design: FACS-RNAseq of 2 Drosophila lines, with two technical replicates per line.

first: Aaron

last: Johnson

first: Sabine

last: Dietmann


title: Dietary cholesterol causes inflammatory imbalance and exacerbates morbidity in mice infected with influenza A virus

city: Urbana

first: Andrew

middle: J

last: Steelman

state: IL

address: 1201 West Gregory

institute: University of Illinois

summary: Influenza is a common cause of pneumonia-induced hospitalization and death, but how host factors function to influence disease susceptibility or severity has not been fully elucidated. Cellular cholesterol levels may affect the pathogenesis of influenza infection as cholesterol is crucial for viral entry and replication, as well as immune cell proliferation and function. But there is still conflicting evidence on the extent to which dietary cholesterol influences cholesterol metabolism. Here, we examined the effects of a high cholesterol diet in modulating the immune response to influenza A virus (IAV) infection in mice. Mice were fed a standard or a high cholesterol diet for five weeks before inoculation with mouse-adapted human IAV (Puerto Rico/8/1934), and tissues were collected at days 0, 4, 8, and 16 post-infection. Cholesterol-fed mice exhibited dyslipidemia characterized by increased levels of total serum cholesterol prior to infection and decreased triglycerides after infection. Cholesterol-fed mice also displayed increased morbidity compared to mice fed a control diet, which was neither a result of immunosuppression nor changes in viral load. Instead, transcriptomic analysis of the lungs revealed that dietary cholesterol caused upregulation of genes involved in viral-response pathways and leukocyte trafficking, which coincided with increased numbers of cytokine-producing CD4+ and CD8+ T cells and infiltrating dendritic cells. Morbidity as determined by percent weight loss was highly correlated with numbers of cytokine-producing CD4+ and CD8+ T cells as well as granulocytes. Taken together, hypercholesterolemia promoted IAV morbidity via exaggerated cellular immune responses that were independent of viral load.

overall_design: 54 samples total. Control group (Normal diet) vs Treatment group (Cholesterol diet, 2%) at 4 time points (Day 0, Day 4, Day 8, Day 16 post-infection). n=6-9 animals per group

first: Allison

middle: Y

last: Louie

first: Joseph

last: Tingling

first: Evan

last: Dray

first: Jamal

last: Hussain

first: Daniel

middle: B

last: McKim

first: Kelly

middle: S

last: Swanson


title: RNA sequencing identifies a novel microRNA pc-3p-116 involved in ovarian development and fecundity in Bactrocera dorsalis [miRNA-seq]

city: Wuhan

first: Weiwei

last: Zheng

state: Hubei

address: Shizishan Street No.1

department: College of Plant Science and Technology

institute: Huazhong Agricultural University

summary: Female reproductive potential is crucial for a population to multiply. MicroRNAs (miRNAs) have been demonstrated to be critical regulators in the post-transcriptional regulation of numerous biological processes, including reproduction. However, these studies mainly focus on model species. The oriental fruit fly, Bactrocera dorsalis, is a highly invasive pest in East Asia and the Pacific. Thus, it is of great significance to identify miRNAs involved in reproduction in this notorious pest. In this study, high-throughput sequencing was carried out to identify miRNAs potentially involved in reproductive development in female B. dorsalis. Eight miRNA libraries were established in the ovary and fat body from four developmental stages [1 days (d), 5 d, 9 d, and 13 d post-eclosion]. 116 and 84 miRNAs were found to be differentially expressed in ovary and fat body, respectively, during sexual maturation of female adults. The Gene Ontology analysis of the target genes involved in oogenesis and lipid particle accounted for 33% and 15% respectively  . Among these differentially expressed miRNAs, we found five highly expressed miRNAs that are shared in the ovary and fat body that comprised four (miR-305-3p, miR-317-3p, miR-2779, and miR-305) conserved and one novel (Bdo-pc-3p-116) miRNA. Quantitative polymerase chain reaction results revealed that Bdo-pc-3p-116 was found to be specifically expressed in the ovary and down-regulated during sexual maturation. Injection of agomir-pc-3p-116 resulted in arrested ovarian development, and reduced egg deposition and progeny viability in B. dorsalis. CYP6a14 and endophilin B were confirmed to be the targets of pc-3p-116 via dual-luciferase assay and expression profiling. RNAi depletion of CYP6a14 led to reproductive defects similar to those caused by the injection of pc-3p-116 agomir. Thus, pc-3p-116 might play a critical role in female reproduction by targeting CYP6a14 and endophilin B and serve as a monitor to control CYP6a14 and endophilin B1 mRNA levels. Our data will not only provide abundant miRNAs as well as target genes for molecular research in female reproduction but also promote environment-friendly control strategies for this agricultural pest.

overall_design: Eight samples total, two biological replicates

first: Rui

last: Zhang

first: Haozhe

last: Li


title: Bulk RNA-seq of human kidney organids in different culture conditions

summary: To date strategies aiming to modulate cell to extracellular matrix (ECM) interactions during organoid derivation remain largely unexplored. Here, renal decellularized extracellular matrix (dECM) hydrogels have been fabricated from porcine renal cortex as new biomaterials to enrich cell-to-ECM crosstalk during the onset of kidney organoid differentiationfrom human pluripotent stem cells (hPSCs).Renal dECM derived hydrogels are used in combination with hPSC-derived renal progenitor cellsto define new approaches for 2D and 3D kidney organoid differentiation.

overall_design: Bulk RNA-seq of human kidney organoids

first: Nuria

last: Montserrat

first: Elena

last: Garreta


title: Angiogenesis blockade overcomes acquired KRAS G12D inhibitor resistance driven by KRAS-PI3Kγ interaction

status: Public on Mar 02 2025

first: Ji-Won

last: Kim

overall_design: RNA-seq profiling the interactions between patient derived organoids and endothelial cells

first: Sung-Hyun

last: Hwang

first: Mingyun

last: Bae


title: Pumilio regulates synaptic protein function in a 3’UTR-dependent manner [Pum_3RIPseq]

first: Valérie

last: Hilgers

address: Stübeweg 51

institute: MPI of Immunobiology and Epigenetics

summary: The regulation of RNA is crucial for spatiotemporal control of gene expression in neurons, but how the correct localization, levels, and function of synaptic proteins are achieved is not well understood. In this study, we globally investigate the role of alternative 3'UTRs in regulating RNA localization in the synaptic regions of the Drosophila brain. We identify direct mRNA targets of the translational repressor Pumilio, finding that mRNAs bound by Pumilio encode proteins enriched in synaptosomes. Pumilio differentially binds to RNA isoforms of the same gene, where shorter 3'UTRs tend to localize to the synapse, and longer 3'UTRs remain in the neuronal soma. Disruptions in 3'UTR isoform localization and axon outgrowth occur in pumilio mutant neurons. Our results reveal a mechanism of isoform-dependent protein function, demonstrating how neurons can achieve high protein complexity with a restricted set of genes.

overall_design: This study assesses 3' mRNA-sequencing and proteomic raw data of D. melanogaster "Synaptosome" fractions, in addition to Pumilio 3'xRIPseq data of D. melanogaster head isolates, to assess the role of Pumilio in the localization of mRNAs, and translation of Pumilio asociated proteins at the synapse. Input controls samples were obtained for all three data sources.

first: Dominika

last: Grzejda

first: Anton

last: Hess

last: Rezansoff

first: Sakshi

last: Gorey

first: Judit

last: Carrasco

first: Carlos

last: Alfonso-Gonzalez

first: Stylianos

last: Tsagkris

first: Lena

last: Neuhaus

first: Mengjin

last: Shi

first: Hasan Can

last: Ozbulut

first: Friederike-Nora

last: Vögtle

first: Andreas

last: Vlachos


title: Pumilio regulates synaptic protein function in a 3’UTR-dependent manner [Synap_3seq]

first: Andrew


title: Hypercholesterolemia-induced LXR Signaling in Smooth Muscle Cells (SMCs) Contributes to Atherosclerotic Lesion Remodeling and Regulates Vascular and Visceral SMC Function

city: New Haven

last: Fernandez-Hernando

address: 10 Amistad St

institute: Yale University

summary:
BACKGROUND: Vascular smooth muscle cells (VSMC) are the most abundant cell type in the artery’s media layer and regulate vascular tone and lesion remodeling during atherogenesis. Like monocyte-derived macrophages, VSMCs accumulate excess lipids and contribute to the total intimal foam cell population in human coronary plaque and mouse aortic atheroma. While there are extensive studies characterizing the contribution of lipid metabolism in macrophage immunometabolic responses in atherosclerotic plaques, the role of VSMC lipid metabolism in regulating vascular function and lesion remodeling in vivo remains poorly understood.
METHODS: We re-analyzed publicly available single-cell RNA sequencing (scRNA-seq) data from mouse atherosclerosis studies and found Liver X receptor (LXR) signaling in VSMCs was continuously activated during atherogenesis. We thus generated mice with an inducible SMC-specific knockout of LXR/LXR on a fate mapping background by crossbreeding LXRf/fLXRf/f mice with Myh11-CreERT2;mTmGf/f mice. Mice were administered with tamoxifen (1 mg/day) for 10 consecutive days and followed by a 2-week resting period to induce CreERT2 mediated recombination. To induce hypercholesterolemia and atherosclerosis, we injected Myh11-CreERT2;mT/mGf/f;LXRf/fLXRf/f mice and Myh11-CreERT2;mT/mGf/f mice with AAV8-PCSK9 and fed them with a Western diet (WD) for 16 weeks. Metabolic, immunocytochemistry and genomic analysis were conducted to assess lesion size and morphology and unravel the molecular mechanism by which LXR in VSMC contributes to lesion formation.
RESULTS: Deficiency of LXR in SMCs under hypercholesterolemic condition influenced lesion remodeling by altering the fate of de-differentiated SMC and promoting the accumulation of VSMC-derived transitional cells. This phenotypic switching is accompanied with reduced index of plaque stability characterized by larger necrotic core area and reduced fibrous cap thickness. Moreover, SMC-specific LXR deficiency impaired vascular function and caused visceral myopathy characterized by bladder maladaptive remodeling and gut lipid malabsorption.
CONCLUSIONS: We unveil an essential role of hypercholesterolemia-induced LXR signaling in atherosclerotic lesion remodeling, controlling the fate decision of VSMCs and regulating vascular and visceral SMCs functions.

overall_design: Smooth muscle cell specific LXR knockout (LXRiSMC) and WT mice were used in this study to explore the role of LXR on vascular smooth muscle cell phenotypic switching. Mice used for single cellRNAseq were injected with AAV8-PCSK9 to raise total cholesterol levels and fed a western type diet for 16 weeks. Aorta were harvested from these mice for single cell sequencing.

first: Hanming

last: Zhang

first: Yajaira

last: Suarez


title: Pumilio regulates synaptic protein function in a 3’UTR-dependent manner

city: Freiburg

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

overall_design: Refer to individual Series


title: Unique B Cell and Germinal Center Responses in Mice with Severe versus Mild Orientia tsutsugamushi Infection

city: Galveston

first: Lynn

last: Soong

address: 301 University Blvd MRB 3.132

institute: University of Texas Medical Branch

summary: We performed RNAseq on total RNA extracted from spleens isolated from mice infected with Orientia tsutsugamushi Karp or Gilliam strains, as well as mock-infected mice to investigate the unique transcriptomic environments elicited by two different Orientia tsutsugamushi strains.

overall_design: We then performed differential expression analysis and gene set enrichment anaylsis using data obtained by RNA-seq of mock infected and O. tsutsugamushi Karp- and Gilliam-infected mice (D4, D8, and D12).

first: Casey

last: Gonzales

first: Yuejin

last: Liang


title: Multi-omics profiling of human endothelial differentiation reveals gene regulatory program in vasculature-related dysfunctions [in situ Hi-C]

city: Daejeon

first: Gyeongsik

last: Park

state: Daejeon

address: 291 Daehak-ro, Yuseong-gu

department: Biology

institute: KAIST

summary: The epigenomic remodeling and the pathological dysfunctions involved in vascular endothelial cell (EC) differentiation are largely unknown. Here, we construct extensive transcriptomic and epigenomic landscapes for human EC differentiation, sectioned at highly dense time points. This led to the identification of 42,309 differentiation stage-specific cis-regulatory elements (cREs), and revealed potential upstream regulators involved in EC lineage specification. Strikingly, our heritability analysis shows cREs transiently activated during EC commitment harbor a significant amount of germline genetic variants related to cardiovascular, inflammatory, and autoimmune disorders, and colorectal cancer. We generate high-resolution 3D chromatin contact maps to accurately pin-down functional targets of these risk variants. Our integrative analysis leveraging clinical samples of colorectal tumor and normal mucosa demonstrates that differentiation stage-specific cREs may mediate transition of vascular ECs to tumor-associated ECs (TECs). This work provides a comprehensive view of chromatin dynamics related to vascular EC formation and its pathological associations.

overall_design: 3D chromatin contact profiles representing differentiation of human embryonic stem cells to mature vascular endothelial cells

first: Andrew Jeoungun

last: Lee

first: Gou-Young

last: Koh

first: Inkyung

last: Jung


title: Jamaican fruit bats’ (Artibeus jamaicensis) competence for Ebola virus but not Marburg virus is driven by intrinsic differences in viral entry and IFN-I signaling antagonism

city: Bethesda

first: Philip

last: Murphy

state: MD

address: 10 CENTER DR RM 11N111

department: National Institute of Allergy and Infectious Diseases

institute: National Institutes of Health

summary: Ebola virus (EBOV) and Marburg virus (MARV) are zoonotic filoviruses that cause hemorrhagic fever in humans. Bat species in both Chiropteran suborders host filoviruses, suggesting that bats may have coevolved with this viral family. Correlative data implicate bats as natural EBOV hosts, but neither a full-length genome nor an EBOV isolate has been found in any bats sampled. Here, we modelled filovirus infection in the Jamaican fruit bat (JFB), Artibeus jamaicensis. Bats were inoculated with either EBOV or MARV through a combination of oral, intranasal, and subcutaneous routes. EBOV-infected bats supported systemic virus replication and shed infectious virus orally. In contrast, MARV replicated only transiently and was not shed. In vitro, JFB cells replicate EBOV more efficiently than MARV, and MARV infection induced innate antiviral responses that EBOV efficiently suppressed. Experiments using VSV pseudoparticles or replicating VSV expressing the EBOV or MARV glycoprotein demonstrated an advantage for EBOV entry and replication early, respectively, in JFB cells. Overall, this study describes filovirus species-specific phenotypes for both JFB and their cells.

overall_design: RNA from livers of negative control or 3 DPI EBOV- or MARV-infected bats was used for analysis. mRNA was sequenced and differential expression between each was assessed.

first: Sarah

last: van Tol

first: Julia

first: Robert

last: Fischer

first: Shane

last: Gallogly

first: Trenton

last: Bushmaker

first: Amanda

last: Griffin

first: Jonathan

middle: E

last: Schulz

first: Aaron

last: Carmody

first: Lara

last: Myers

first: Daniel

last: Crowley

first: Caylee

middle: A

last: Falvo

first: Jade

middle: C

last: Riopelle

first: Arthur

last: Wickenhagen

first: Chad

last: Clancy

first: Jamie

last: Lovaglio

first: Carl

last: Shaia

first: Greg

last: Saturday

first: Jessica

last: Prado-Smith

first: Yi

last: He

first: Justin

last: Lack

first: Craig

last: Martens

last: Anzick

first: Lon

middle: V

last: Kendall

first: Tony

last: Schountz

first: Raina

last: Plowright

first: Andrea

last: Marzi

first: Vincent

last: Munster


title: Effect of depletion of HuR on gene expression in mouse head and neck squamous cell carcinoma (mHNSCC) cells

city: Charleston

first: Stefano

last: Berto

state: SC

address: 68 President Street

department: Neuroscience

institute: Medical University of South Carolina

summary: RNA-binding protein HuR (Hu Antigen R, alias ELAVl1) is a primary post-transcriptional gene regulatory protein. Its overexpression promotes the progression of multiple cancers, including head and neck squamous cell carcinoma (HNSCC). Although HuR promotes cancer progression, the crosstalk between HuR and immune cells during oral tumorigenesis remains elusive. Here, we investigated the effects of HuR on oral tumors and immune cell functions in vitro and in vivo using a transgenic HuR knockout (KO) mouse model. We observed that CRISPR/Cas9 mediated knockout of HuR in murine oral carcinoma cells failed to form colonies and tumors. The HuR KO cells exhibited reduced tumor volume with high infiltration of CD8+ and fewer CD4+ T cells, demonstrating that HuR may control the immune response during oral cancer progression.  Next, oral epithelial tissue-specific HuR KO failed to form neoplastic growth compared with the control 4NQO-induced tumor mice. The HuR KO mice show decreased Tregs and increased IFNg compared to WT tumor-bearing mice. The transcriptome obtained from RNA-Seq showed that multiple cancer pathways were altered between WT and HuR KO oral cancer cells. The HuR KO group showed significant negative regulation of transcription factors and positive regulation of extracellular matrix and cell adhesion pathways, demonstrating its significance in HNSCC. Specifically, positive regulation of HuR target mRNAs that encode proteins responsible for cancer stem cells associated with cell adhesion was observed and confirmed through mRNA half-life analysis. Finally, HuR inhibitor pyrvinium pamoate reduces the tumor burden through activation of CD8+ and reduction in CD4+ in tumors, demonstrating that anti-tumor functions were associated with HuR KO. Together, the results of this study indicate that HuR-mediated oral carcinogenesis, dependent on immune dysfunction and cell adhesion pathway, suggests that inhibition of HuR may enhance the anti-tumor potential for oral cancer therapeutics.

overall_design: To investigate the cooperative function of HuR in the HNSCC cell lines in which HuR has been knocked out by Crispr/Cas9. We then performed gene expression profiling analysis using data obtained from RNA-seq of control and KO cells with Biological triplicates.

first: Mrinmoyee

last: Majumder

first: Viswanathan

last: Palanisamy


title: Semaglutide attenuates obesity-induced impact on intestinal epithelium

city: Beijing

first: Ye-guang

last: Chen

address: Tsinghua Road, Medical Building

department: School of life science

institute: Tsinghua University

summary: Obesity, a complex ailment, has demonstrated promising weight reduction outcomes with glucagon-like peptide-1 receptor agonists (GLP-1RA) drugs like semaglutide. Nevertheless, their intricate mechanisms remain elusive. In this study, we constructed single-cell transcriptomic profiles of intestinal epithelium from individuals with normal and high BMI, revealing significant transcriptomic and metabolic alterations.

overall_design: In this study, we constructed a comprehensive single-cell transcriptomic atlas of human intestinal epithelium in individuals with normal weight as well as those classified as overweight with a body mass index (BMI) from 25 to 29.9, and obese individuals with a BMI of 30 or greater, and reveals significant transcriptomic and metabolic alterations by comparative analysis

first: Wanlu

last: Song

first: Yalong

last: Wang

first: Zhi

last: Fang


title: Gene expression of single cell of rhabdomyolysis induced acute kidney injury cells

city: TOULOUSE

first: JULIE

last: BELLIERE

state: OCCITANIE

address: 1 avenue Pr Jean Poulhès, CHU TOULOUSE

institute: INSERM U1297

summary: We used single cell RNA sequencing to identify the immune cells and especially mononuclear phagocytic cells affecting rhabdomyolysis induced acute kidney injury.

overall_design: kidneys were obtained from control mice or RM-AKI mice, rinced with cold PBS and digested to obtain cellular suspension as described in the manuscript. Cells were stained with anti-CD45-PE-Vio770  and Viobility 405/452 Fixable Dye. CD45+ live cells were sorted using BD InfluxTM cell sorter (BD Biosciences, Sortware software) (pressure 20 psi, nozzle 100 µm). The single cell suspensions were prepared by following the recommendations  of the Single Cell 3' Reagent Kit User Guide (10X Genomics, Pleasanton, California USA).

first: Julie

last: Belliere

first: Margot

last: Zahm

first: Snigdha

last: Rao

first: Joost

middle: P

last: Schanstra

first: Jean

last: Saulnier-Blache


title: Disease-associated changes in the lung microbiome in patients with early chronic obstructive pulmonary disease

city: Shanghai

first: manyi

last: pan

address: Manufacturing Bureau Road, Shanghai

department: Department of Respiratory and Critical Care Medicine

institute: Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine

summary: Chronic obstructive pulmonary disease (COPD) is associated with airway inflammation and microbiota dysbiosis. However, the function of lung microbiome alteration in early COPD remains unclear. This study is the first to characterize the lower respiratory tract microbiota in early COPD patients via bronchoalveolar lavage fluid (BALF) samples. By using full-length 16S sequencing, we found that the lung microbiome of early COPD patients had lower bacterial richness and significant compositional differences than did that of the healthy smoker controls. Streptococcus was the most robustly distinguished genus in early COPD patients and was associated with decreased lung function and increased host local inflammation. Furthermore, a murine cigarette smoke model of early COPD revealed that Streptococcus mitis promotes the progression of early COPD. Single-cell transcriptomics revealed that Streptococcus mitis increased emphysematous destruction of the lung parenchyma in a mouse early COPD model by regulating the function of alveolar type II (AT2) cells and macrophages. Therefore, targeting the lower airway microbiota in combination with smoking cessation may be a potential therapeutic approach for early COPD.

overall_design: We established a cigarette smoke-induced murine COPD model and investigated the role of Streptococcus mitis by intratracheally inoculating mice with S.mitis every 3 days for 4 weeks, followed by exposure to smoke for 12 weeks; single-cell RNA sequencing was then performed on lung samples from control, smoke-exposed, and smoke-exposed S.mitis-colonized mice


title: ATMP-classified, scalable, autologous cell spray for the treatment of skin wounds and assessment of its effects on wound healing clinically and on molecular level

city: Helsinki

first: Esko

last: Kankuri

address: Haartmaninkatu 8

department: Department of Pharmacology

country: Finland

institute: University of Helsinki

summary: We collected biopsies from patients undergoing split-thickness skin graft harvesting. The first biopsy was collected from the intact skin before wounding and the second and third from the donor site wound on 14th and 21st day post-operatively. A genome-wide microarray was then executed from each sample, and the gene profiles of each time point were compared.

overall_design: For the characterization of donor site wound healing and evaluation of cell treatment effects, burn patients between 36 and 62 years were included in the study and 3 mm punch biopsies were obtained from each patient over time. The first biopsy was taken before skin harvesting from the area to be wounded, the second 14 and the third 21 days post-operatively from the donor wound. The donor site wounds were divided into treatment side (cell spray treatment) and control side (no treatment). A thin layer of fibrin sealant was sprayed to both wound areas. The obtained biopsies were processed for human full genome microarray and bioinformatics data analyses.

first: Kristo

last: Nuutila

first: Shintaro

last: Katayama


title: A lack of commensal microbiota influences the male reproductive tract intergenerationally in mice

city: Philadelphia

first: Natalie

middle: Alyce

last: Trigg

state: Pennsylvania

address: 421 Curie Blvd

institute: Children's Hospital of Philadelphia

summary: The microbiome encompasses the array of microorganisms inhabiting various niches in the body and is necessary for numerous physiological processes, including normal metabolism and a functioning immune system. Not only does the absence of a microbiome in mice impact the exposed animals but also inherited phenotypes in successive generations of progeny, suggesting that the absence of a microbiome impacts the germline and gametes. Indeed, recent research has identified a role of the gut microbiome in contributing to male fertility, in both healthy and disease states. While this link is beginning to be established, the impact of the microbiome on the male reproductive tract remains understudied. Here, we utilized a germ-free mouse model to examine the influence of the absence of microbes on the male reproductive tract. In contrast to mice with an established microbiome, germ-free mice display decreased testicular weight and the prevalence of an epididymitis-like inflammation phenotype. These histopathological changes are accompanied by transcriptomic dysregulation in the reproductive tract of germ-free mice, particularly in the cauda epididymis. Moreover, such transcriptomic changes are transmitted to the next generation with high correlation of gene expression in the cauda epididymis between germ-free mice and their conventionalized (microbiome-restored) male offspring, when compared to control mice. Ultimately, our findings identify the reproductive sequalae of males without a functional microbiome and additionally in their conventionalized offspring, suggesting that the paternal microbiota is an underappreciated contributor to male reproductive function.

overall_design: To investigate the influence of microbiota on the male reproductive tract we collected testis from specific pathogen free control mice (SPF) and germ-free mice (GF) (n = 3-4) and caput and cauda epididymis tissue from SPF, GF and male offspring from GF x SPF parents for RNA-seq. We also investigated the role of T and B cells in directing gene expression changes by performing RNA-seq on caput and cauda epididymal tissue from Rag2 knockout male mice.

last: A Trigg

first: Simon

last: Zhou

first: Jordan

last: Harris

first: Madeline

middle: N

last: Lamonica

first: Molly

last: Nelson

first: Michael

last: Silverman

first: Taku

last: Kambayashi

first: Colin

last: Conine


title: BrCHR39, a novel chromatin remodeling ATPase, positively regulates apical dominance in Brassica rapa

city: Zhengzhou

first: Wei

last: Zhu

address: 100 Science Avenue

institute: Zhengzhou University

summary:
Purpose: The transcriptomic profiling was performed to explain the release of apical dominance due to cell division among stem and bud in BrCHR39-silenced lines .
Methods: The stems and axillary buds of the wild-type and BrCHR39-silenced brassica rapa grown for 8 weeks were collected, then immediately dipped in liquid nitrogen for RNA extraction using the TRIzol reagent (Invitrogen, Waltham, MA, USA) and pooled for sequencing. All samples were collected in three biological replicates. After DNaseI treatment, poly (A) mRNA was isolated with oligo (dT) magnetic beads and fragmented to short fragments. Then the first and second strand cDNA were synthesized. And library construction was completed after adding base A and sequencing adapters, end repair, and recovery of the target fragments. Agilent Bioanalyzer 2100 system (Agilent Technologies, CA, USA) was used to detect the insert size of the library. The qualified cDNA libraries were sequenced by synthesis (SBS) technology using Illumina HiSeq 2500 high-throughput Sequencing platform.
Results: In this study, auxin-related genes in the stems of transgenic plants showed a trend of decreasing expression from the beginning of biosynthesis to signal transduction. However, genes about auxin and cytokinin in the buds of transgenic plants were up-regulated totally. Thus we speculated that apical dominance is attributable to differential expression of multiple hormones.
Conclusions: Our study provides a detailed analysis of biological replication of transgenic and wild-type transcriptome produced by RNA-seq technology. And specific pathways and associated genes were identified. Our results showed that RNA-seq based transcriptome characterization can provide ideas and basis for subsequent studies to analyze the causes of phenotypic variation. In this study, the reason why the silencing of BrCHR39 gene leads to the weakening of apical dominance was that the auxin signaling pathway was inhibited.

overall_design: The mRNA profiles of 8-week-old stems and buds of wild type (WT) and transgenic Brassica rapa.

first: Fang

last: Wei


title: Expression data from splenic T cells  at day7 during MOG-induced mouse EAE model

first: Xiaoxia

last: Wang

state: Shanghai

address: No.280 South Chongqing Road, Room 811, Building No.5 (West Area)

department: Department of Immunology and Microbiology

institute: Shanghai Jiao Tong University School of Medicine

summary: Regulatory T cells (Tregs) are indispensable for maintaining immunological homeostasis and preventing autoimmune diseases. IRE1a is an ER-resident transmembrane protein kinase/endoribonuclease that initiates a critical signaling branch of the unfolded protein response (UPR).  We aim to search for genes change of Tregs and Teffs from WT (Foxp3Cre)and IRE1a-/-(KO) mice in the context of MOG-induced experimental autoimmune encephalomyelitis.  Our results reveal an important mechanism that links the IRE1a branch of the UPR to experimental autoimmune encephalomyelitis(EAE) model, showing IRE1a affects Tregs suppressive function via mediating HDAC9 upregulation. Our findings suggest that Treg IRE1a is a valuable therapeutic target against multiple sclerosis and other autoimmue diseases.

overall_design: Transcriptome analysis of splenic Tregs (CD4+CD25hiYFP+) and Teffs (CD4+CD25-YFP-)  of WT and IRE1a-/-(KO) at EAE7d

first: Hao

last: Cheng

first: Fangming

first: Yichao

last: Han


title: Effect of oral administration of Si-based agent on renal mRNA expression.

city: Suita

first: Ryo

last: Tanaka

state: Osaka

department: Department of Urology

institute: Osaka University Graduate School of Medicine

summary: Oral administration of Si-based agents produces large amounts of hydrogen under alkaline conditions in the intestinal tract. Hydrogen removes reactive oxygen species and reduces oxidative stress. It is also known that oxidative stress is involved in the progression of renal fibrosis. We reported that oral administration of Si- based agent suppressed renal fibrosis using UUO model. mRNA expression in Sham group, UUO group, and UUO+Si group was evaluated by RNA-seq and functional analysis, and found that fibrosis-related Gene ontology and Pathways related to fibrosis were suppressed by the Si-based agent.

overall_design: Mice were devided to Sham group, UUO group, and UUO+Si group. mRNA expression of each group was evaluated by RNA-seq and functional analysis

first: Ryoichi

last: Imamura

first: Daisuke

last: Motooka


title: Single-cell sequencing quantitative analysis of skin tissues of wild-type and Chrna5-/- mice treated with vaseline

city: Jinan

first: Dianhao

last: Guo

address: 6699 Qingdao Road

department: Institute of Basic Medicine

institute: shandong first medical university

summary:
Purpose: To understand the molecular processes and cell subsets involved in an increase in the psoriatic inflammatory response in Chrna5 signaling compared with WT mice, we performed single-cell sequencing with dorsal skin tissues after vaseline treatment.
Methods: Skin mRNA profiles of wile-type (WT) and cholinergic receptor nicotinic alpha 5 subunit knockout (Chrna5-/-)mice were generated by deep sequencing. The samples of KO and WT mice after vaseline treatment were processed in terms of alignment, barcode assignment, and UMI counting with Cell Ranger, version 3.0.2 (https://github.com/10XGenomics/cellranger) count pipeline.
Results: The cell clustering analysis, the heat map analysis, the cell subpopulations of keratinocytes analysis, the gene enrichment analysis and signal pathway analysis were all carried out. The results of these studies indicated that Chrna5 knockout may have a significant effect on the keratinocytes after vaseline treatment.
Conclusions: These results revealed the potential role of Chrna5 in the occurrence and development of normal skin.

overall_design: Skin mRNA profiles of WT and Chrna5-/- mice treated with vaseline.

first: Jing

first: Xiangying

last: Li

first: Ping

last: Zhang

first: Tao

last: Yang

last: Liu

first: Li

last: Qin

first: Guanghui

last: Ma

first: Xiaobing

first: Huiping

last: Fan

first: Shuhong

last: Huang

first: Ningning

last: Dang


title: Multi-omics analysis of liver molecular dysregulation leading to non-viral related hepatocellular carcinoma development

city: Hiroshima-shi

first: Hikaru

last: Nakahara

address: kasumi 1-2-3, minami-ku

institute: Hiroshima University

summary: Chronic liver diseases exhibit diverse backgrounds, and it is believed that numerous factors contribute to progression to cancer. To achieve effective prevention of non-viral hepatocellular carcinoma, it is imperative to identify fundamental molecular abnormalities at the patient level. Utilizing cancer-adjacent liver tissues obtained from hepatocellular carcinoma patients (chronic liver disease), we conducted RNA-Seq and metabolome analyses. In the chronic liver disease cohort, upregulation of inflammation-associated signals was observed, concomitant with accumulation of acylcarnitine and fatty acid and depletion of NADP+, gamma-tocopherol, and dehydroisoandrosterone-3-sulfate-1 (DHEAS). To minimize heterogeneity, we performed multi-omics clustering, successfully categorizing the chronic liver disease cases into two distinct subtypes. Subtype 1 demonstrated elevated inflammatory levels, whereas Subtype 2 included a disproportionately high proportion of elderly cases. Furthermore, RNA-Seq analysis revealed upregulation of inflammatory signals in Subtype 1, while both subtypes exhibited downregulation of fatty acid metabolism. Metabolome analysis indicated a tendency of increased acylcarnitine levels in Subtype 1 and augmented fatty acid accumulation in Subtype 2. Validation of differentially expressed genes using the Gene Expression Omnibus (GEO) dataset revealed the potential for amelioration through supplementation with antioxidants such as epigallocatechin gallate (ECGC).

overall_design: RNAseq analysis was performed using liver tissue adjacent to cancer from 56 patients with hepatocellular carcinoma (chronic liver disease) and liver tissue from 13 patients without hepatocellular carcinoma as controls.

first: Ono

last: Atsushi


title: RNA sequencing identifies a novel microRNA pc-3p-116 involved in ovarian development and fecundity in Bactrocera dorsalis

first: Weiwei

last: Zheng

institute: Huazhong Agricultural University


title: RNA sequencing identifies a novel microRNA pc-3p-116 involved in ovarian development and fecundity in Bactrocera dorsalis [RNA-seq]

summary: Female reproductive potential is crucial for a population to multiply. MicroRNAs (miRNAs) have been demonstrated to be critical regulators in the post-transcriptional regulation of numerous biological processes, including reproduction. However, these studies mainly focus on model species. The oriental fruit fly, Bactrocera dorsalis, is a highly invasive pest in East Asia and the Pacific. Thus, it is of great significance to identify miRNAs involved in reproduction in this notorious pest. In this study, high-throughput sequencing was carried out to identify miRNAs potentially involved in reproductive development in female B. dorsalis. Eight miRNA libraries were established in the ovary and fat body from four developmental stages [1 days (d), 5 d, 9 d, and 13 d post-eclosion]. 116 and 84 miRNAs were found to be differentially expressed in ovary and fat body, respectively, during sexual maturation of female adults. The Gene Ontology analysis of the target genes involved in oogenesis and lipid particle accounted for 33% and 15% respectively  . Among these differentially expressed miRNAs, we found five highly expressed miRNAs that are shared in the ovary and fat body that comprised four (miR-305-3p, miR-317-3p, miR-2779, and miR-305) conserved and one novel (Bdo-pc-3p-116) miRNA. Quantitative polymerase chain reaction results revealed that Bdo-pc-3p-116 was found to be specifically expressed in the ovary and down-regulated during sexual maturation. Injection of agomir-pc-3p-116 resulted in arrested ovarian development, and reduced egg deposition and progeny viability in B. dorsalis. CYP6a14 and endophilin B were confirmed to be the targets of pc-3p-116 via dual-luciferase assay and expression profiling. RNAi depletion of CYP6a14 led to reproductive defects similar to those caused by the injection of pc-3p-116 agomir. Thus, pc-3p-116 might play a critical role in female reproduction by targeting CYP6a14 and endophilin B and serve as a monitor to control CYP6a14 and endophilin B1 mRNA levels. Our data will not only provide abundant miRNAs as well as target genes for molecular research in female reproduction but also promote environment-friendly control strategies for this agricultural pest.

overall_design: Eight samples total, two biological replicates

first: Rui

first: Haozhe


title: Transdermal nanolipoplex simultaneously inhibits subcutaneous melanoma growth and suppresses systemically metastatic melanoma by activating host immunity

city: Hsinchu

first: Ling-ya

state: Taiwan

address: 1001 University Road

country: Taiwan

institute: National Yang Ming Chiao Tung University

summary: The aim of this experiment is exploring the efficacy melanoma treatment by skin administration and anti-tumor metastatic ability.

overall_design: Tumor cells were inoculated in C57BL/6J female mouse,then the tumor mass was treated by different drugs.

first: Chia-Hung

last: Chen

first: Ling-Ya

first: Hsiao-Hsuan

first: Sih-Cheng

first: Pin-Rong

first: Pei-Chun

last: Shen

first: Po-Ya

last: Chuang

first: Hsiao-Yen

first: Yi-Syuan

last: Wu

first: Shun-Long

last: Weng

first: Kai-Yao

first: Tzu-Han

first: Kuang-Wen

last: Liao


title: Dexmedetomidine Inhibits Fear Memory Consolidation via the Astrocyte-Specific Srebf1-Phgdh Pathway in the Prelimbic Prefrontal Cortex

status: Public on Mar 01 2025

city: Wuhan

first: Feiyang

last: Zhang

address: Bayi Road #299

institute: 武汉大学

summary: Background Post-traumatic stress disorder (PTSD) is a common mental disorder for which effectiveinterventions remain limited. Therefore, we set out to study whether anestheticdexmedetomidine could mitigate fear memory consolidation, part of PTSD, in mice andexplored underlying mechanisms. Methods Adult C57BL/6 male mice received dexmedetomidine (40 μg kg-1, i.p.) immediately following fear conditioning. An auditory-cued memory test in a different context wasconducted next day. RNA sequencing and neuromolecular analyses of prelimbicprefrontal cortex were performed. Molecular pathways were validated using specific gene knockdown, coupled with detailed phenotype analysis. Results Dexmedetomidine significantly reduced freezing time in mice during the auditory-cued memory test compared to control condition (15 [11.73] % vs. 59.67 [14.46] %,P=0.0018) and decreased concentrations of synaptic-related proteins (10.69 [1.27]vs. 7.97 [1.29], P<0.0001) and levels of dendritic spine density. Additionally, dexmedetomidine alleviated anxiety-like behavior and sensorimotor gating function impairment in mice after fear conditioning. These effects correlated with reduced nuclear translocation of sterol regulatory element-binding protein 1 (Srebf1) in astrocytes, but not neurons nor microglia, within the prelimbic prefrontal cortex of mice, leading to downregulation of phosphoglycerate dehydrogenase (Phgdh), a downstream target gene. Specific knockdown of Srebf1 or Phgdh in astrocytes without the treatment of dexmedetomidine inhibited fear memory consolidation and the associated synaptic plasticity in mice. Conclusions Dexmedetomidine mitigated PTSD-like behavior in mice by inhibiting fear memory consolidation through the astrocyte-specific Srebf1-Phgdh pathway in the prelimbic prefrontal cortex. These findings will promote more research toward to understanding of using anesthetic to treat PTSD and the underlying mechanism

first: Ke

last: Li

first: Wei

last: Wei

first: Xin

first: Siyuan

last: Wang

first: Xiang

first: Mian

last: Peng


title: Discovery of Competent Chromatin Regions in Human Embryonic Stem Cells [scRNA-seq]

city: New York

first: Julian

last: Pulecio

state: NY

institute: Memorial Sloan Kettering Cancer Center

summary: It remains unknown whether adult-tissue enhancers are pre-established in early embryonic stages. Using CRISPR-activation screens, we found that embryonic stem cells (ESCs) contain transcriptionally competent chromatin regions (CCRs), poised to activate lineage genes before differentiation. CCRs serve as functional enhancer precursors within topological chromatin domains and are pre-marked by pluripotency factors OCT4/NANOG (ON) and DNA demethylation factors QSER1/TET1 (ONQT). We demonstrate that ON and ONQT signatures identify CCRs at a genome-wide scale. CCRs can be harnessed to convert ESCs into differentiated cell types, showcasing their potential for practical applications. Our findings provide insight into how ESCs rapidly establish transcriptional activity during lineage specification, expand our understanding of cellular plasticity and provide the basis to identify adult enhancers in undifferentiated cells.

overall_design: Single-cell 10x genomics experiments were performed using hESCs after interrogating candidate CCRs through CRISPRa screens. We employed a gRNA backbone inspired on the CROP-Seq system that allows the dual identification of gRNAs and single-cell transcriptomics. gRNA and transcriptome libraries were generated and sequenced. Final analyses were done using CellRanger and the SCEPTRE algorithm.

first: Renhe

last: Luo

last: Hu

first: Jielin

last: Yan

first: Danwei

last: Huangfu