title: Glioblastoma and Cerebral Organoids: Development and Analysis of in vitro Model for Glioblastoma Migration

city: Brno

first: Katerina

last: Amruz Cerna

state: Czech Republic

address: Kamenice 3

department: Department of Histology and Embryology

country: Czech Republic

institute: Faculty of Medicine, Masaryk University

summary:
It is currently challenging to adequately model the growth and migration of glioblastoma using 2D in vitro culture systems as they quickly lose the original, patient-specific identity and heterogeneity.
However, with the advent of 3D cell cultures and human induced pluripotent stem cells (iPSCs)-derived cerebral organoids (COs), studies demonstrate that the glioblastoma-cerebral organoid (GLICO) co-culture model helps to preserve the phenotype of the patient-specific tissue.
Here we aimed to set up such a model using mature COs and develop a pipeline for subsequent analysis of co-cultured glioblastoma.
Our data demonstrates that the growth and migration of the glioblastoma cell line within the mature COs are significantly increased in the presence of extracellular matrix proteins, shortening the time needed for glioblastoma to initiate migration.
We also describe in detail the method for the visualization and quantification of these migrating cells within the GLICO model. Lastly, we show that this co-culture model (and the human brain-like microenvironment) can significantly transform the gene expression profile of the established U87 glioblastoma cell line into proneural and classical glioblastoma cell types.

overall_design: Comparative gene expression analysis of three biological replicates of GFP+ cells sorted from of GLICO model (each sample consisting of 5 GLICOs; co-cultivation for 40 days) and controls - three biological replicates of U87-GFP spheroids cultivated alone without co-culture with cerebral organoids.

first: Veronika

last: Fedorova

last: Pospisilova

first: Tereza

last: Vanova

first: Pavel

last: Abaffy

first: Jiri

last: Sedmik

first: Jan

last: Raska

first: Simona

last: Vochyanova

first: Zuzana

last: Matusova

first: Jana

last: Houserova

first: Lukas

last: Valihrach

first: Zdenek

last: Hodny

first: Dasa

last: Bohaciakova


title: Genome-wide analysis of differentially expressed profiles of mRNAs, lncRNAs and circRNAs in aorta samples of F. nucleatum-infected mice

status: Public on Feb 22 2023

city: Chengdu

first: Keyi

last: Zhang

address: No. 14, section 3, Renmin South Road

country: China

institute: West China Hospital of Stomatology, Sichuan University

type: Expression profiling by high throughput sequencing

type: Non-coding RNA profiling by high throughput sequencing

summary: Periodontitis is an independent risk factor for atherosclerosis, and F. nucleatum is one of the periodontal pathogens. Several studies have confirmed that non-coding RNAs could affect all aspects of AS disease progression, including lipid metabolism, foam cell formation, cell necrosis, etc. However, no studies have explored whether F. nucleatum could affect AS disease progression by regulating non-coding RNAs. In this study, we intend to acquire mRNAs, lncRNAs and circRNAs expression profiles of aorta samples of AS mice from the F. nucleatum group and the Control group by next-generation sequencing(NGS) and perform bioinformatics analysis. Results revealed that 465 mRNA expression were up-regulated and 382 mRNA expression were down-regulated significantly. Some lncRNAs and circRNAs could suppress the binding of miRNA with target genes in post-transcriptional regulation. By integrating with DE-miRNAs-DEGs pairs and screening the common miRNAs, and mRNAs, lncRNAs, circRNAs that have targeted and negatively correlated relationship with the common miRNAs, lncRNA-miRNA-mRNA (including 34 DE-miRNAs, 42 DE-lncRNAs, and 111 DE-mRNAs) and circRNA-miRNA-mRNA (including 19 DE-miRNAs, 49 DE-circRNAs, and 87 DE-mRNAs) regulatory co-expression networks were constructed. GO enrichment analysis was performed on the differentially expressed mRNAs, which were found to be related to molecular functions, biological processes and cellular components such as protein binding, nucleus, postsynaptic dense zone, protein phosphorylation. KEGG analysis showed that they were related to ErbB signaling pathway, neurotrophic factor signaling pathway, glucagon signaling pathway and apoptosis signaling pathway. This suggested that F. nucleatum could promote the development of atherosclerosis  through non-coding RNAs network regulation.

overall_design: Comparative gene expression profiling analysis of mRNA, lncRNAs and circRNAs sequencing data for F. nucleatum-infected aorta samples of mice and control group.

first: Lin

last: Liu

first: Jieyu

last: Zhou

first: Peiyao

last: Wu

first: Lei

last: Zhao

first: Yafei


title: Cell Lineage Specific Mitochondrial Resilience During Mammalian Organogenesis

city: Cambridge

first: Malwina

last: Prater

address: Hills Rd

department: MRC MBU

country: United Kingdom

institute: University of Cambridge

summary: Mitochondrial activity differs markedly between organs, but it is not known how and when this arises. Here we show that cell lineage specific expression profiles involving essential mitochondrial genes emerge at an early stage in mouse development, including tissue-specific isoforms present before organ formation. However, the nuclear transcriptional signatures were not independent of organelle function. Genetically disrupting intra-mitochondrial protein synthesis with two different mtDNA mutations induced cell lineage specific compensatory responses, including molecular pathways not previously implicated in organellar maintenance. We saw down regulation of genes whose expression is known to exacerbate the effects of exogenous mitochondrial toxins, indicating a transcriptional adaptation to mitochondrial dysfunction during embryonic development. The compensatory pathways were both tissue and mutation specific, and under the control of specific transcription factors which promote organelle resilience. These are likely to contribute to the tissue specificity which characterizes human mitochondrial diseases, and are potential targets for organ-directed treatments.

overall_design: Heteroplasmic immortalized MEFs carrying the m.5024C>T mutation were cultured under standard laboratory conditions. Five high heteroplasmy populations and five low heteroplasmy populations were selected as biological replicates. 1x107 cells per MEF line were harvested following trypsinisation and total RNA was extracted. Following QC to confirm RNA integrity, libraries were constructed using polyA capture and pooled for sequencing. 50bp paired-end read sequencing was performed using one lane of an Illumina NovaSeq6000 SP flowcell.

first: Stephen

middle: P

last: Burr

first: Angelos

last: Glynos

first: James

middle: B

last: Stewart

first: Patrick

middle: F

last: Chinnery


title: Effect of depletion or transgenic overexpression of nup133 or elys on zygotic genome activation (ZGA) during zebrafish early development

city: Beijing

first: Weimin

last: Shen

address: Tsinghuayuan park

institute: School of life science, Tsinghua University

summary: To investigate the function of nuclear pore complex (NPC) in the regulation of zygotic genome activation (ZGA), we established mutants of nucleoporins, including maternal and zygotic mutant of nup133 (MZnup133) and maternal mutant of elys (Melys),  for maternal depletion by CRISPR/Cas9, and transgenic embryos of nup133 (Tgnup133) for maternal overexpression through Tol2 mediated method.  We then performed gene expression profiling analysis using data obtained from RNA-seq of wildtype, MZnup133, Melys and Tgnup133 at three time points.

overall_design: Comparative gene expression profiling analysis of RNA-seq data for zebrafish wildtype and MZnup133, Melys or Tgnup133 embryos at 3 hpf (hours post fertilization), 4 hpf and 4.5 hpf.

first: Anming

last: Meng


title: EXPRESSION DATA OF PROSTATE CELL LINES DU145 AND LNCAP AND HUMAN ASTROCYTES CO-CULTURED

status: Public on Feb 23 2023

city: Rio de Janeiro

first: Pedro

last: Nicolau Neto

state: RJ

address: 37 Andre Cavalcanti Street

department: PCM

country: Brazil

institute: INCA

summary:
EVALUATING THE GENE EXPRESSION PROFILE OF PROSTATIC TUMOR CELL IN CO-CULTURE WITH HUMAN ASTROCYTE AND THE TRANSCRIPTIONAL REPROGRAMMING IN ASTROCYTS BY CONTACTING WITH TUMOR CELLS
DNA MICROARRAY WAS APPLIED AIMING TO EVALUATE THE GENE EXPRESSION PROFILE

overall_design: AFTER CO-CULTURE TOTAL TUMOR CELLS AND ASTROCYTE RNA WERE EXTRACTED AND THE GENE EXPRESSION PROFILE WAS ANALYZED USING AFFYMETRIX MICROARRAY

first: E

last: Oliveira-Bastos

first: A

last: Palumbo


title: Methylation Signature Implicated in Immuno-Suppressive Activities in Tubo-Ovarian High-Grade Serous Carcinoma

city: Rochester

first: Ellen

middle: L

last: Goode

state: MN

address: 200 First Street SW

department: Quantitative Health Sciences

country: USA

institute: Mayo Clinic

type: Methylation profiling by genome tiling array

summary: Background: Better understanding of prognostic factors in tubo-ovarian high-grade serous carcinoma (HGSC) is critical, as diagnosis confers an aggressive disease course. Variation in tumor DNA methylation shows promise predicting outcome, yet prior studies were largely platform-specific and unable to evaluate multiple molecular features.    Methods: We analyzed genome-wide DNA methylation in 1,040 frozen HGSC, including 325 previously reported upon, seeking a multi-platform quantitative methylation signature which we evaluated in relation to clinical features, tumor characteristics, time to recurrence/death, extent of CD8+ tumor-infiltrating lymphocytes (TILs), gene expression molecular subtypes, and gene expression of the ATP-binding cassette transporter TAP1.   Results: Methylation signature was associated with shorter time to recurrence, independent of clinical factors (N=715 new set, HR 1.65, 95% CI 1.10-2.46, p=0.015; N=325 published set HR 2.87, 95% CI 2.17-3.81, p=2.2 x 10-13) and remained prognostic after adjustment for gene expression molecular subtype and TAP1 expression (N=599, HR 2.22, 95% CI 1.66-2.95, p=4.1 x 10-8). Methylation signature was inversely related to CD8+ TIL levels (p=2.4 x 10-7) and TAP1 expression (p=0.0011) and was associated with gene expression molecular subtype (p=5.9 x 10-4) in covariate-adjusted analysis.   Conclusions: Multi-center analysis identified a novel quantitative tumor methylation signature of HGSC applicable to numerous commercially available platforms indicative of shorter time to recurrence/death, adjusting for other factors. Along with immune cell composition analysis, these results suggest a role for DNA methylation in the immunosuppressive microenvironment.    Impact: This work aids in identification of targetable epigenome processes and stratification of patients for whom tailored treatment may be most beneficial.

overall_design: Bisulphite converted DNA from 36 samples were hybridised to the Illumina Infinium Methylation EPIC and 325 samples were hybridised to the Illumina InfiniumHumanMethylation 450 BeadChip. Data for 4 samples are not included in GEO submission (3 samples due to consent and 1 sample as a potential sample mix-up). All the other samples were previously made publicly available, as follows: TCGA methylation data are available via the cBioPortal for Cancer Genomics (https://www.cbioportal.org/; RRID:SCR_014555); other data are available on Gene Expression Omnibus (GEO; RRID:SCR_005012) under the following accession numbers: GSE65820, GSE211686, GSE72021, and GSE1333556.


title: Prx1 cell subpopulations identified in various tissues with diverse quiescence and activation ability following fracture and BMP2 stimulation

city: Boston

first: Yu

state: MA

address: 72 East Concord Street

institute: Boston University

summary: The expression of Prx1 has been used as a marker to define the skeletal stem cells (SSC) populations found within the bone marrow and periosteum that contribute to bone regeneration. However, Prx1 expressing SSCs (Prx1-SSCs) are not restricted to the bone compartments, but are also located within the muscle and able to contribute to ectopic bone formation.  Little is known however, about the mechanism(s) regulating Prx1-SSCs that reside in muscle and how they participate in bone regeneration. This study compared both the intrinsic and extrinsic factors of the periosteum and muscle derived Prx1-SSCs and analyzed their regulatory mechanisms of activation, proliferation, and skeletal differentiation. There was considerable transcriptomic heterogeneity in the Prx1-SSCs  found in muscle or the periosteum however in vitro cells from both tissues show tri-lineage (adipose, cartilage and bone) differentiation. At homeostasis, periosteal derived Prx1 cells were proliferative and low levels of BMP2 were able to promote their differentiation, while the muscle derived Prx1 cells were quiescent and refractory to comparable levels of BMP2 that promoted periosteal cell differentiation. The transplantation of Prx1-SCC from muscle and periosteum into either the same site from which they were isolated, or their reciprocal sites showed that periosteal cell transplanted onto the surface of bone tissues differentiated into bone and cartilage cells but was incapable of similar differentiation when transplanted into muscle. Prx1-SSCs from the muscle showed no ability to differentiate at either site of transplantation. Both fracture and ten times the BMP2 dose was needed to promote muscle-derived cells to rapidly enter the cell cycle as well as undergo skeletal cell differentiation. This study elucidates the diversity of the Prx1-SSC population showing that cells within different tissue sites are intrinsically different. While muscle tissue must have factors that promote Prx1-SSC to remain quiescent, either bone injury or high levels of BMP2 can activate these cells to both proliferate and undergo skeletal cell differentiation.  Finally, these studies raise the possibility that muscle SSCs are potential target for skeletal repair and bone diseases.

overall_design: All samples for RNA seq were obtained from mouse femur and tibia within the same animals. Cells from each tissue were sorted into three populations by FACS. There are three replicates for each population.

first: Adrian

last: Ilinski

first: Beth

last: Bragdon

first: Louis

middle: C

last: Gerstenfeld


title: Epigenetic profiles of HSCs transduced with control or Runx3-expressing lentivirus

city: Oxford

first: Claus

last: Nerlov

address: John Radcliffe Hospital, University of Oxford

department: MRC Molecular Haematology Unit

institute: Weatheral Institute of Molecular Medicine

type: Genome binding/occupancy profiling by high throughput sequencing

summary: To determine if ectopic expression of Runx3 can correct deficient lymphoid output in aged HSCs, we examine the chromatin profile of aged HSC transduced with control or Runx3-expressing lentivirus.

overall_design: Control or Runx3-expressing lentivirus was used to infect cKit-enriched bone marrow cells from aged (24 months) mice. Transduced cells were transplanted into lethally irradiated mice. After 16 weeks of transplantation, transduced donor-derived HSCs (LSK Flt3-CD150+CD48-CD45.2+hCD2+) were FACS sorted for ATAC-seq profiling.

first: Yiran

first: Xiying

last: Ren

first: Bowen

last: Zhang


title: miRNA-seq of miRNAs expression in aorta samples of F. nucleatum-infected mice

first: Keyi

summary: Periodontitis is an independent risk factor for atherosclerosis, and F. nucleatum is one of the periodontal pathogens. Several studies have confirmed that miRNAs can affect all aspects of AS disease progression, including lipid metabolism, foam cell formation, cell necrosis, etc. However, no studies have explored whether F. nucleatum can affect AS disease progression by regulating miRNA expression. In this study, we intend to acquire miRNA expression profiles of aorta samples of AS mice by next-generation sequencing(NGS) and perform bioinformatics analysis to compare the differential expression of miRNAs in the F. nucleatum group and the Control group. Results revealed that 16 microRNAs differentially expressed, of which 13 miRNAs expression were down-regulated and 3 miRNAs expression were up-regulated. GO enrichment analysis showed that they were related to negative regulation of superoxide anion production, protein binding and positive regulation of myocardial apoptosis. KEGG enrichment analysis showed that they were related to necrotizing apoptosis, neurotrophic factor signaling pathway, Nod-like receptor signaling pathway, apoptosis, Wnt signaling pathway, Ras signaling pathway and autophagy, etc. This suggests that F. nucleatum may regulate AS progression through miRNAs.

overall_design: Comparative gene expression profiling analysis of miRNA-seq data for F. nucleatum-infected aorta samples of mice and control group.

first: Lin

last: Liu

first: Jieyu

last: Zhou

first: Peiyao

last: Wu

first: Lei

last: Zhao

first: Yafei


title: Epigenetic profiles of young vs old HSCs

summary: Here we examine the chromatin landscapes of HSCs from young (2 months) vs old (24 months) mice bone marrow.

overall_design: To determine the chromatin accessibility changes in HSCs during ageing, we FACS sorted HSCs (LSKCD150+CD48-) from young and old mouse bone marrow for bulk ATAC-seq.

first: Simona

last: Valletta


title: Chronic alcohol metabolism results in DNA repair infidelity and cell-cycle-induced senescence in neurons

city: Hong Kong

first: Hei-Man Kim

last: Chow

address: Room 604, Mong Man Wai Building, CUHK

department: School of Life Sciences

country: Hong Kong

institute: The Chinese University of Hong Kong

summary: Chronic and excessive binge-like drinking is a risk factor to pathological cognitive decline and dementia, but the mechanism underlying the prolonged and lasting effect of alcohol even in abstainers remains elusive. This study investigates how ethyl alcohol directly results in metabolic reprograming and persistent physiological changes in brain cells that underlies such effect.

overall_design: RNA sequencing of brain cortex samples from wildtype mice subjected to a binge-like drinking paradigm or vehicle control.

first: Hei-Man

middle: K

first: Ka-Li

middle: J

last: Sun


title: Effect of nuclear pore complex (NPC) blockage by WGA treatment on zygotic genome activation (ZGA) during zebrafish early development

first: Weimin

last: Shen

summary: To investigate the function of nuclear pore complex (NPC) in the regulation of zygotic genome activation (ZGA), we microinjected medium dosage of WGA in zebrafish embryos at 1-cell stage to block NPC function.  We then performed gene expression profiling analysis using data obtained from RNA-seq of control or WGA treated embryo at comparable developmental time point (4.3 hours post fertilization (hpf) ) or develomental stage (dome).

overall_design: Comparative gene expression profiling analysis of RNA-seq data for zebrafish control embryo at 4.3 hpf of dome stage and WGA treated embryos at 4.3 hpf (developmental time matched) or 5 hpf (dome-like stage).

first: Anming

last: Meng


title: CD5 expression by dendritic cells directs T cell immunity and sustains immunotherapy responses

city: Los Angeles

first: Feiyang

last: Ma

state: CA

address: 610, Charles Young Dr East, TLSB 3000C

department: Molecular Biology Institute

institute: UCLA

summary: The induction of proinflammatory T cells by dendritic cell (DC) subtypes is critical for anti-tumor responses and effective immune checkpoint blockade (ICB) therapy. Here we show that human CD1c+CD5+ dendritic cells are reduced in melanoma-affected lymph nodes, with CD5 expression on DCs correlating with patient survival. Activating CD5 on DCs enhanced T-cell priming and improved survival after immune checkpoint blockade therapy. CD5+ DC numbers increased during ICB treatment, and low IL-6 levels promoted their de novo differentiation. Mechanistically, CD5 expression by DCs was required to generate optimally protective CD5hi T helper and CD8+ T cells; further, deletion of CD5 from T cells dampened tumor elimination in response to ICB therapy in vivo. Thus, CD5+ dendritic cells are an essential component of optimal immune checkpoint blockade therapy.

overall_design: single cell RNA sequencing comparing myeloid cells from tumor-involved and uninvolved tissues.

first: Mingyu

last: He

first: Eynav

last: Klechevsky


title: Peripheral blood T helper cells circulate with pathogenic tissue resident T helper cells in chronic GVHD

city: Duarte

first: wei

last: chen

address: 1500 E Duarte Rd

department: Cancer Biology-BRI

institute: City of Hope National Medical Center

summary: Chronic graft versus host disease (cGVHD) is a systemic autoimmune-like syndrome.  The role of Tph cells in the pathogenesis of cGVHD has not been examined, although previous studies have shown that cGVHD is characterized by loss of Tfh cells. Here, we show that in cGVHD patients and in a murine model that reflects characteristic features of human cGVHD, the proportions of Tph cells among CD4+ T cells in the blood were expanded.  These cells augmented memory B cell differentiation and production of IgG via IL-21. Adoptive transfer experiments showed recirculation between Tph in the blood and tissue-resident T helper (Trh) cells in GVHD target tissues.  The TCR repertoires of blood Tph cells and Trh cells in GVHD target tissues of mice were highly overlapping.

overall_design: Irradiated BALB/c recipient in receiving TCD-BM alone or plus 0.2M Thy1.2 cells from C57BL/6 H2Kb donor to establish No GVHD and cGVHD mouse model. PD1hiCXCR5- Tph cells from blood, CD69+ or CD69- PSGL1loPD1hi Trh cells from liver and lung of cGVHD recipients; Tfh cells from the spleen of No GVHD recipients were sorted out. mRNA from sorted cells were then isolated and processed for TCR repertiores sequencing.

first: Defu

last: Zeng

first: Xiwei

first: Xiaohui

last: Kong


title: CD8+ T cell-1 dependent antitumor response boosted by dual blockade of PD-1 and VGFR2 following EGFR-tyrosine kinase inhibitors against lung cancer with Egfr mutation

city: Okayama

first: Shuta

last: Tomida

address: 2-5-1 Shikata-cho, Kita-ku

department: Center for Comprehensive Genomic Medicine

country: Japan

institute: Okayama University Hospital

summary: We showed that CD8+ T cell-dependent antitumor response was induced by an EGFR-tyrosine kinase inhibitor (TKI) against syngeneic Egfr-mutant NSCLC tumors and that the effect was further pronounced by the sequential dual blockade of PD-1 and vascular endothelial growth factor receptor 2 (VEGFR2).

overall_design: The subcutaneous tumors harboring Egfr exon 19 deletions were passaged using C57BL/6J mice, then the mice were randomly assigned to groups that were treated with the vehicle, gefitinib, DC101, and/or 4H2. The tumor volume (width2 × length/2) was determined periodically.

first: Kazuya

last: Nishii

first: Kadoaki

last: Ohashi

first: Katsuyuki

last: Kiura


title: RNAs sequencing revealing the gene expression profiling in kidney tissues between diabetic kidney disease and control

city: Jinan

first: jinxiu

last: Hu

address: jingwuweiqi

institute: Shandong Provincial Hospital

summary: Diabetic kidney disease (DKD), a progressive kidney disease, is a major complication associated with diabetes and has become the leading cause of chronic kidney disease in China. Increasing evidences have demonstrated that lncRNAs play vital roles in kidney diseases, including DKD. To search for new ncRNAs involved in DKD, we performed gene expression profiling in the kidney tissues isolated from DKD patients and non-diabetic renal cancer patients undergoing surgical resection by RNA sequencing. And we identified 65 DEncRNAs (29 upregulated and 36 downregulated in DKD) and 171 DEmRNAs (72 upregulated and 99 downregulated in DKD).This study will provide insights into the prevent and treatment of DKD in the future.

overall_design: kidney tissues from renal biopsies of 3 DKD patients and normal tissues from 3 non-diabetic renal cancer patients undergoing surgical resection

first: Rong

last: Wang

first: Zhimei

last: Lv


title: Single cell ATAC-seq of mouse retinal CX3CR1+ myeloid cells for Naive, PBS and 4xLPS treatment

city: Montreal

first: Mike

last: Sapieha

state: Quebec

address: 5415 Boul. L'Assomption

country: Canada

institute: Hôpital Maisonneuve-Rosemont

summary: We report epigenetic changes in the chromatin accessibility landscape of retinal myeloid cells from mice preconditioned with 4xLPS injections persist after the initial inflammation has subsided. We compared the data of scATAC-seq performed on nuclei extracted from sorted CX3CR1+ retinal cells from mice 3 days after CNV induction, preconditioned with either PBS or 4xLPS 1 month before, or Naïve retinas without CNV induction, preconditioned with PBS. After quality control, filtering and dimension reduction, a two-dimensional UMAP was performed on the remaining 835, 821, and 588 cells in the PBS, 4xLPS, and Naive groups respectively. Unbiased clustering was applied using Leiden algorithm, which partitioned CX3CR1+ myeloid cells into 8 distinct clusters (C1–C8). Based on previously described cell-specific gene signatures, we identified microglia (clusters C1, C2 and C3), monocytes (clusters C4 and C5), and macrophages (cluster C6). Gene expression scores identified C4 as circulating monocytes and C5 as a mixture of classical and inflammatory monocytes. The three microglial populations (C1, C2, and C3), harbor the greatest epigenetic diversity following induction of CNV or preconditioning. GSEA analysis revealed that the C2 subpopulation was characterized by considerable enrichment in opened chromatin regions corresponding to genes coding for inflammation-related pathways. In contrast, the C1 subpopulation showed higher numbers of closed chromatin in genes coding for inflammatory processes. Moreover, when compared to the C1 and C2 subpopulations, C3 had open chromatin regions only in two gene sets coding for inflammation-related pathways, and three gene sets with closed chromatin regions. Together, these data demonstrate that the chromatin landscape of retina-resident microglia is impacted differently by both the prior systemic exposure to LPS and by CNV.

overall_design: scATAC-seq of FACS-sorted CX3CR1+ retinal cells from mice 3 days after CNV induction, preconditioned with either PBS or 4xLPS 1 month before, or Naïve retinas without CNV induction, preconditioned with PBS.

first: Masayuki

last: Hata


title: Analysis of changes in transcriptomes of the rat medial prefrontal cortex tissues (mPFC) in vehicle group, chronic mild stress (CMS) group, and CMS+Phloretin group

first: Yutao

last: Yang

state: Beijing

address: No.10, You An Men Wai Xi Tou Tiao

department: Department of Neurobiology

institute: Capital Medical University

summary:
Purpose: The goals of this study are to investigate the effects of Phloretin (PHL) on the changes of genes in rat mPFC tissues between Vehicle group, CMS group, and CMS+PHL group.
Methods: Vehicle group: Rats received vehicle by oral gavage for 2 weeks, and then were left undisturbed for 3 weeks except for necessary procedures, including handling and routine cleaning for 3 weeks. CMS group: Rats received vehicle by oral gavage for 2 weeks, and then were subjected to eight different stressors for 3 weeks in a random order, including foot shock, water deprivation, cold water swimming, food deprivation, restraint, clip tail, light/dark cycle reversal, and cage tilt. CMS+PHL group: Rats were pre-treated with 20 mg/kg. Phloretin for 2 weeks, and then exposed to above eight stressors randomly together with 20 mg/kg Phloretin for 3 weeks. In each group, we collected mPFC tissues from 3 rats and total RNA was extracted. RNA integrity was assessed using the RNA Nano 6000 Assay Kit of the Bioanalyzer 2100 system. The clustering of the index-coded samples was performed on a cBot Cluster Generation System using TruSeq PE Cluster Kit v3-cBot-HS (Illumina) according to the manufacturer’s instructions. After cluster generation, the library preparations were sequenced on an Illumina Novaseq platform and 150 bp paired-end reads were generated.
Results: We found that Phloretin treatment changed some gene expression, especially in neuronal plasticity, compared with CMS group.

overall_design: mPFC mRNA profiles of Vehicle group, CMS group, and CMS+PHL group.


title: RNA pulldown target circGLS2

city: Shanghai

first: Xi

last: Chen

address: 8th Panshan Road

institute: Second Military Medical University

summary: Hepatocellular carcinoma is a poor prognosis cancer leading to death, with high rate of recurrence after curative therapy. The functions of Covalently closed circular RNA (circRNAs) in HCC recurrence have remained largely unknown. In this study, we generated multi-omics data to explore the circRNAs involving in the HCC recurrence.

overall_design: miRNA sequencing for circGLS2-specific and negative probe pulldown

first: Jianhua

last: Yin

first: Guangwen

last: Cao


title: Epigenetic profiling of multipotent progenitors [Bulk_ATACseq_MPP2]

first: Claus

last: Nerlov

summary: Fate-restricted HSCs generated distinct phenotypic MPP2. Here we report the epigenetic profiles of Vwf+Gata1+ and Vwf-Gata1+ MPP2.

overall_design: MPP2 subpopulations (Vwf+Gata1+ and Vwf-Gata1+) from adult mouse bone marrow (8-12 weeks) were FACS sorted for bulk ATAC-seq (500 cells per replicate and 4 replicates per population).

first: Yiran

last: Meng

first: Joana

last: Carrelha

first: Sten

middle: E

last: Jacobsen


title: Epigenetic profiles of fate-restricted HSCs [Bulk_ATACseq_HSC]

summary: HSC subtypes with distintic lineage restrictions have been previously reported. Here we examine the chromatin landscapes of HSC subtypes with P-restricted, PEM-restricted or multilineage in vivo output.

overall_design: Single cell transplantations of Vwf+ HSCs from mouse bone marrow were performed to generated primary recipients showing lineage-restricted reconstitution over 16 weeks : P-restricted, PEM-restricted and multilineage. Donor-derived Gata1- HSCs were isolated from recipients' bone marrow for bulk ATAC-seq (500 cells per replicate, 3 replicates for PLT-HSC, 6 replicates for PEM-HSC, 4 replicates for MUL-HSC).


title: Transcriptional Antagonism by CDK8 Inhibition Improves Therapeutic Efficacy of MEK Inhibitors

first: Gabriela

last: Alexe

address: 415 Main St.

department: Computational Biology and Bioinformatics

institute: Broad Institute

summary: Aberrant RAS/MAPK signaling, a common driver of oncogenesis, can be therapeutically targeted with clinically approved MEK inhibitors. Single agent therapy ultimately results in tumor outgrowth in most settings and combination therapies are required to achieve significant clinical benefit in most advanced cancers. Here we focus on identifying MEK inhibitor-based combination therapies in RAS-mutant neuroblastoma. Mutations that activate the RAS/MAPK signaling pathway, while rare at diagnosis, are more frequent in relapsed neuroblastoma. More than 50% of children with high-risk neuroblastoma ultimately relapse and treatment options for relapsed neuroblastoma are limited so most children with relapsed disease do not survive. Here we use a genome-scale CRISPR-Cas9 functional genomic screen to identify genes that, when lost, sensitize RAS-mutant neuroblastoma to MEK inhibition.  We discover that loss of either CCNC or CDK8, two members of the mediator kinase module, sensitizes neuroblastoma to MEK inhibition. Furthermore, we demonstrate that small molecule kinase inhibitors of CDK8 improve response to MEK inhibitors in vitro and in vivo in RAS-mutant neuroblastoma and other adult solid tumors, suggesting that the addition of CDK8 inhibitors could improve clinical outcome. Using transcriptional profiling, we unexpectedly find that loss of CDK8 or CCNC antagonizes the transcriptional signature induced by MEK inhibition. When combined, loss of CDK8 or CCNC prevents the compensatory upregulation of pro-growth gene expression induced by MEK inhibition. These findings propose a new therapeutic combination for RAS-mutant neuroblastoma and may have clinical relevance for other RAS-driven malignancies.

overall_design: SK-N-AS cells were infected with a single vector containing Cas9, sgCCNC and sgCDK8. Cells were then selected with puromycin. Nine days after infection, cells were treated with either DMSO or 3 nM trametinib in triplicate.

first: Kimberly

last: Stegmaier


title: Establishment of Primary Liver Cancer Organoids and Application on Sorafenib Resistance

summary: Current in vitro models of primary liver cancer fail to recapitulate the key characteristics of original cancer. We construct the long-term organoids culture from tumor tissue of primary liver cancer (PLC) patients with varieties of subtypes. PLC organoids retain the histopathological features of originating tumor. Organoids transplantation proved that the tumorogenic potential and histological characteristics of PLC organoids are well preserved in vivo. PLC organoids are amenable for preclinical drug screening test and identification of mammalian target of rapamycin (mTOR) inhibitor compound as a potential therapeutic treatment for PLC. Besides, we also establish sorafenib-resistant hepatocellular carcinoma (HCC) organoids to clarify the mechanisms that drive resistance. In conclusion, PLC organoids models provide a platform for drug development for PLC and theoretical basis for HCC resistance.

overall_design: Paired sorafenib-resistant and -sensitive tumor-derived organoids from 4 HCC patients

first: Linfeng

last: Xian

first: Pei

last: Zhao

first: Zhimin

last: Wei


title: Transcriptome sequencing data of tumors and paired adjacent tissues from HCC patients

overall_design: Transcriptome RNA sequencing data of tumors and paired adjacent tissues from HCC patients


title: Epigenetic profiling of hematopoietic progenitors [Bulk_ATACseq_Prog]

summary: To generate lineage-specific chromatin signatures, here we profiled the chromatin landscapes of lineage-committed progenitors.

overall_design: Hematopoietic progenitors from adult mouse bone marrow (8-12 weeks) were FACS sorted for bulk ATAC-seq (1000 cells per replicate, 3 replicates each population).


title: circRNA sequencing data of tumors and paired adjacent tissues from HCC patients


title: Impact of oligodendrocyte secreted factors on hippocampal GABAergic neurons: an electrophysiological and transcriptomic study

city: Paris

first: Noémie

last: Robil

address: 29, rue du Faubourg Saint-Jacques

department: Paris Biotech Santé

country: France

institute: GenoSplice technology

summary: In the present work, we gain insight into the impact of oligodendrocyte secreted factors on hippocampal GABAergic neuron physiology, and performed patch-clamp recordings followed by single-cell RNA sequencing of neurons. Our results demonstrate that the GABAergic neuron excitability is influenced by glial cells and oligodendrocyte-secreted factors. Moreover, we show specific ion channels alterations and find a correlation with electrophysiological parameters suggesting possible mechanisms for the OCM-induced regulation of neuronal function.

overall_design: hippocampal neurons cultured with glial cells or purified neurons treated or not with oligodendrocyte conditioned medium

first: Elisa

last: Mazuir

first: Louis

last: Richevaux

first: Mérie

last: Nassar

first: Pierre

last: de la Grange

first: Catherine

last: Lubetzki

first: Desdemona

last: Fricker

first: Nathalie

last: Sol-Foulon


title: Upregulation of Profilin 2 on HDAC6 overexpression in mouse GC-1 cells and its putative role in germ cell migration in the testis

status: Public on Feb 21 2023

city: Bangalore

first: Genotypic

last: technology

state: Karnataka

address: 259, Apoorva 4th cross,80 feet Road,RMV 2ND STAGE

country: India

institute: Genotypic Technology

summary: HDAC6 was overexpressed in GC-1spg cells, which represent the stage between type B spermatogonia and primary spermatocyte, and its effect on germ cell transcriptome was investigated by microarray

overall_design: Agilent Mouse Whole Genome 8x60k Microarray: AMADID: 74809

first: Pratibha

last: Verma

first: Smita

last: Yevate

first: Priyanka

last: Parte


title: Transcriptome analysis of miRNA–mRNA interactions revealed regulation of multiple signaling pathways in genetically improved farmed tilapia (GIFT, Oreochromis niloticus) gill tissues under hypoxia stress

city: Wuxi

first: Jun

last: Qiang

state: Jiangsu

address: 9 Shanshi East road

institute: Freshwater Fisheries Research Center, Chinese Academy of Fishery Sciences

summary: Dissolved oxygen (DO) is the basis of fish survival, and proper DO level is an important condition to ensure the normal growth of fish. Hypoxic environment is prone to disturb the normal breathing and metabolism of fish, which in turn affects their growth and survival. Gill tissue is the respiratory organs of fish and is in direct contact with the external environment. However, there are few reports on the molecular regulatory mechanism of genetically improved farmed tilapia (GIFT, Oreochromis niloticus) gill tissues in response to hypoxia. Here, we first examine the hypoxia-induced damage of gill tissue by hematoxylin-eosin staining, and then constructed miRNA and mRNA libraries of GIFT gill tissue at 96h of hypoxia stress by a high-throughput sequencing technology, each library has three biological replicates. Gill lamellae of GIFT showed capillary rupture and red blood cell enlargement and overflow under hypoxia stress. Transcription sequencing results showed that the clean reads of miRNA libraries were 9,627,953-13,544,660; the clean reads of mRNA libraries were 43,817,776-53,130,102. Based on the miRNA-mRNA pairs screening principles and mRNA sequencing results, we selected and verified seven differentially expressed miRNAs and their potential target genes. The sequencing results were consistent with the qRT-PCR validation results. These selected miRNA-mRNA pairs are mainly concentrated in the signaling pathways of immune response and metabolic regulation. This study provides new insights into the mechanisms of fish adaptation under hypoxic stress.

overall_design: GIFT used in the experiment was divided into two groups: the acute experimental group and the control group, each group has four replicates. The design of hypoxia stress  were referenced by Yuan et al. Each experimental group was placed in a 500L tank with a density of 30 tails/tank, and the dissolved oxygen conditions were the same as the acclimation condition. Based on the real-time readings of the dissolved oxygen meter in the experiment, the dissolved oxygen was controlled by adjusting the rate of nitrogen and air charged into the water. The acute experimental group reduced the dissolved oxygen to (1. 02 ± 0. 10) mg · L- within 30 minutes 1. The culture conditions of the control group were the same as acclimation condition, and they were fed normally during the experiment. The acute experimental group and the control group were sampled at 96 h after hypoxia stress, and 4 fish were randomly selected from each tank. When sampling, the experimental fish was deeply anesthetized with MS-222, and the second right gill arch were dissected out on the sterilization operation platform, divided into two, and quickly placed in a 1.5 mL centrifuge tube in liquid nitrogen. Quick-freeze used by liquid nitrogen, and then transfer to -80 ℃  refrigerator for storage. In addition, two fish from each tank were randomly collected to sample the second right gill arch, rinsed with physiological saline, and fixed in 4% paraformaldehyde for the preparation of paraffin section.

first: Jie

last: He

first: Yi-Fan

last: Tao

first: Jin-Wen

last: Bao

first: Jun-Hao

last: Zhu

first: Pao

last: Xu


title: Transcription profiles of fate-restricted HSCs [Bulk RNAseq HSC]

first: Claus

last: Nerlov

summary: HSC subtypes with distintic lineage restriction have been previously reported. Here we examine the transcriptome profiles of HSC subtypes with P-restricted, PEM-restricted or multilineage in vivo output.

overall_design: Single cell transplantation of Vwf+ HSCs from mouse bone marrow was performed to generated primary recipients showing lineage-restricted reconstitution over 16 weeks: P-restricted, PEM-restricted and multilineage. Donor-derived Gata1- HSCs were isolated from recipients' bone marrow for bulk RNA-seq (100 cells per replicate, 3 replicates for PLT-HSC, 6 replicates for PEM-HSC, 4 replicates for MUL-HSC).

first: Yiran

last: Meng

first: Joana

last: Carrelha

first: Sten

last: Jacobsen


title: Differentially expressed genes upon TbSAC3 depletion

city: Vienna

first: Alwin

last: Koehler

address: Dr.-Bohr-Gasse 3/9

country: Austria

institute: Max F. Perutz Laboratories

summary: This study examines differential expression upon TbSAC3 depletion in Trypanosoma brucei brucei strain 29.13

overall_design: RNA-seq analysis of the TbSAC3 RNAi cell line: induced and uninduced condition. RNAi against firefly luciferase was used as a further control. Biological duplicates of each condition were analysed.

first: Ana

last: Krolo

first: Sini

last: Junttila

last: Köhler


title: Reversal of lactate and PD-1-mediated macrophage immunosuppression controls growth of PTEN/p53-deficient prostate cancer

city: miami

first: RIMPI

last: KHURANA

state: FL

address: Room 6112B, Rosenstiel Medical Science Building (RMSB),1600 NW 10th Avenue

institute: University of miami

summary: Purpose: PTEN loss-of-function occurs in ~50% of metastatic, castrate-resistant prostate cancer (mCRPC) patients, and associated with poor prognosis and responsiveness to standard-of-care therapies and immune checkpoint inhibitors. While PTEN loss-of-function hyperactivates PI3K signaling, combinatorial PI3K/AKT pathway and androgen deprivation therapy (ADT) has demonstrated limited anti-cancer efficacy in clinical trials. Here, we aimed to elucidate mechanism(s) of resistance to ADT/PI3K-AKT axis blockade, and to develop rational combinatorial strategies to effectively treat this molecular subset of mCRPC.  Experimental design: Prostate-specific PTEN/p53-deficient genetically engineered mice (GEM) with established 150-200 mm3 tumors, as assessed by ultrasound, were treated with either ADT (degarelix), PI3K inhibitor (copanlisib), or anti-PD-1 antibody (aPD-1), as single agents or their combinations, and tumors were monitored by MRI and harvested for immune, transcriptomic and proteomic profiling, or ex vivo co-culture studies. Single-cell RNAseq on human mCRPC samples was performed using 10X Genomics platform.  Results: Co-clinical trials in PTEN/p53-deficient GEM revealed that recruitment of PD-1-expressing tumor-associated macrophages (TAM) thwarts ADT/PI3Ki combination-induced tumor control. The addition of aPD-1 to ADT/PI3Ki combination led to TAM-dependent ~3-fold increase in anti-cancer responses. Mechanistically, decreased lactate production from PI3Ki-treated tumor cells suppressed histone lactylation within TAM, resulting in their anti-cancer phagocytic activation, which was augmented by ADT/aPD-1 treatment and abrogated by feedback activation of Wnt/β-catenin pathway. Single-cell RNA-sequencing analysis in mCRPC patient biopsy samples revealed a direct correlation between high glycolytic activity and TAM phagocytosis suppression.   Conclusions: Immunometabolic strategies that reverse lactate and PD-1-mediated TAM immunosuppression, in combination with ADT, warrant further investigation in PTEN-deficient mCRPC patients.

overall_design:
Pb-Cre; PTENfl/fl Trp53fl/fl mice with established prostate tumors were treated with degarelix (0.625 mg/mouse, sc, single dose) + copanlisib (14 mg/kg, iv, every alternate day) + aPD-1 (200 μg/mouse, ip, every alternate day) combination for 28 days

Grant information:
This work was supported by 16CHAL12 (Prostate Cancer Foundation Challenge Award to *A. Patnaik*) and P30CA014599 (National Cancer Institute grant to *E. Markiewicz, M. Zamora, X. Fan*). Schürer and Khurana were supported by grants P30CA240139 (National Cancer Institute), U54HL127624 (National Institutes of Health), U24TR002278 (National Institutes of Health), 9BC13 (Bankhead Coley State of Florida Biomedical Research Program), 16CHAL12 (Prostate Cancer Foundation Challenge Award to *A. Patnaik*) and P30CA014599 (National Cancer Institute grant to *E. Markiewicz, M. Zamora X. Fan*).

first: Kiranj

last: Chaudagar

first: Hanna

middle: M

last: Hieromnimon

first: Rimpi

last: Khurana

first: Brian

last: Labadie

first: Taghreed

last: Hirz

first: Shenglin

last: Mei

first: Raisa

last: Hasan

first: Jordan

last: Shafran

first: Anne

last: Kelley

first: Eva

last: Apostolov

first: Ghamdan

last: Al-Eryani

first: Kate

last: Harvey

first: Srikrishnan

last: Rameshbabu

first: Mayme

last: Loyd

first: Kaela

last: Bynoe

first: Catherine

last: Drovetsky

first: Ani

first: Erica

last: Markiewicz

first: Marta

last: Zamora

first: Xiaobing

last: Fan

first: Stephan

last: Schürer

first: Alex

last: Swarbrick

first: David

last: Sykes

first: Akash

last: Patnaik


title: Small RNA sequencing data of tumors and paired adjacent tissues from HCC patients

first: Xi

last: Chen

first: Jianhua

last: Yin

first: Guangwen

last: Cao


title: Effect of estrogen receptor alpha (ERα) signaling in dendritic cells in modulating autoimmune disease phenotype in animal model of Multiple Sclerosis

city: Urbana

first: Makoto

last: Inoue

state: Il

address: 2001 S Lincoln Ave

institute: University of Illinois at Urbana-Champaign

summary: ERα has been shown to have a protective effect.We found that ERα deficiency in dendritic cells (DCs) of mice induced a phenotype “switch” in EAE, defined by severe neurodegeneration and resistance to interferon beta. Diminished ERα signaling in DCs generate neurotoxic effector CD4+ T cells.

overall_design: Gene expression analysis of RNAseq data from CD4+T cells isolated from WT and ERa KO mice with EAE

first: Yee

last: Khaw

first: Shehata

last: Anwar

first: Jinyan

last: Zhou

first: Tasuku

last: Kawano

first: Po-Ching

last: Lin

first: Ashley

last: Otero

first: Jenny

last: Drnevich

first: Alvaro

last: Hernandez

first: Chris

last: Wright

first: Tomoko

last: Takahashi

first: CheMyong

last: Ko


title: Physiological and molecular characterization of yeast cultures pre-adapted for fermentation of lignocellulosic hydrolysate

city: LUND

first: Daniel

last: Brink

address: Naturvetarvagen 14

department: Applied Microbiology

country: Sweden

institute: Lund University

summary: To reach an economically feasible bioethanol process from lignocellulose, efficient fermentation by yeast of all sugars present in the hydrolysate has to be achieved. However, when exposed to lignocellulosic hydrolysate, Saccharomyces cerevisiae is challenged with a variety of inhibitors that reduce yeast viability, growth and fermentation rate, and in addition damage cellular structures. In order to evaluate the yeast capability to adapt to lignocellulosic hydrolysates and to investigate the yeast molecular response to inhibitors, fed-batch cultivation of an industrial S. cerevisiae strain was performed using either spruce hydrolysate or a sugar medium as feed. The physiological effects of cultivating yeast in spruce hydrolysate was comprehensively studied by assessment of yeast performance in simultaneous saccharification and fermentation (SSF), measurement of furaldehyde reduction activity, assessment of conversion of phenolic compounds and genome wide transcription analysis. The yeast cultivated in spruce hydrolysate developed a rapid adaptive response to lignocellulosic hydrolysate, which significantly improved its fermentation performance in subsequent SSF experiments. Yeast adaptation to hydrolysate was shown to involve induction of NADPH-dependent aldehyde reduction activity and conversion of phenolic compounds during the fed-batch cultivation and these properties were correlated to the expression of several genes encoding oxido-reductase activities, notably AAD4, ADH6, OYE2/3 and YML131w. The other most significant transcriptional changes involved genes involved in transport mechanisms, such as YHK8, FLR1 or ATR1. A large set of genes were found to be associated to transcription factors involved in stress response (Msn2p, Msn4p, Yap1p but also cell growth and division (Gcr4p, Ste12p, Sok2p) that were most likely activated at the post-transcriptional level.

platform_organism:
Schizosaccharomyces pombe
Saccharomyces cerevisiae

overall_design:
Two biological replicates for each of the following conditions:
S. cerevisiae start of fed-batch (0h)
S. cerevisiae hydrolysate fed-batch (9h)
S. cerevisiae hydrolysate fed-batch (18h)
S. cerevisiae sugars fed-batch (9h)
S. cerevisiae sugars fed-batch (18h)

first: João

middle: R

last: Almeida

first: Magnus

last: Wiman

first: Dominik

last: Heer

first: Uwe

last: Sauer

first: Bärbel

last: Hahn-Hägerdal

first: Gunnar

last: Lidén

first: Marie

last: Gorwa-Grauslund


title: Kuiyangling inhibits inflammation by reducing intestinal NETs in mice with ulcerative colitis

city: Shenzhen

first: Dong

last: Zhang

state: GuangDong

address: No. 1, Fuhua Road, Futian street, Futian District, Shenzhen

department: Digestive Department

institute: The Fourth Clinical Medical College of Guangzhou University of Traditional Chinese Medicine

summary: To explore the molecular mechanism of the the Traditional Chinese Medicine compound Kuiyangling on the mouse ulcer model.

overall_design: In this study, we constructed a male mouse model of ulcerative colitis by drinking 3% DSS freely. The mice were divided into normal group, model group, 10 g/kg group of Kuiyangling, and 50 mg/kg group of mesalazine. The experimental period is 7 days. On the 7th day, all mice were killed and intestinal mucosa tissues were collected for sequencing. Two animals were selected from each group for repeated sequencing.

first: Siwei

last: Duan

first: Zhangyou

last: He

first: Shaoju

last: Guo


title: Analysis of the role of Dectin-1 in the development of intestinal tumor-infiltrating myeloid cells and intestinal tumorigenesis

city: Guangzhou

first: Ce

last: Tang

address: No.58, Zhong Shan Er Lu

institute: The First Affiliated Hospital, Sun Yat-sen University

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

overall_design: Refer to individual Series


title: Circular RNAs inhibited the growth and the recurrence of hepatocellular carcinoma

first: Xi

last: Chen


title: Glycolytic Pfkp Acts as Lin41 Protein Kinase to Regulate Embryonic Stem Cell Differentiation

city: Zhengzhou

first: Ruijie

last: Wang

state: Henan

address: Fengchan Road Street

department: Academy of Medical Sciences

institute: Zhengzhou University

summary: To investigate the synergistic role of Pfkp and Lin41 in the regulation of lineage differentiation, we knocked down Pfkp and Lin41 in mESC cells (R1 cells) by shRNAs respectively, and cultured for 6 days to form embryoid bodies (EBs).We then performed transcriptome sequencing of the Pfkp or Lin41 knockdown EBs.

overall_design: Comparative gene expression profiling analysis of RNA-seq data for R1 cells (sh-Pfkp, sh-Lin41, and sh-ctrl).

first: Leixi

last: Cao

first: Hao

last: Gu


title: Analysis of the role of Dectin-1 in the development of intestinal tumorigenesis [RNA-Seq]

summary: To investigate the potential role of Dectin-1 in the development of intestinal tumorigenesis, we used Dectin-1 deficient (Clec7a–/–, KO) mice under germ-free (GF) condition and  azoxymethane (AOM) and 3 cycles of dextran-sodium-sulfate (DSS)-induced mouse colorectal tumor model to compare with wild-type (WT) mice.

overall_design: WT and KO mice under germ-free condition were admnistrated with AOM (10mg/g) and 3 cycles of 1% DSS for 36 weeks. Colorectal polyps and non-polyp tissues were collected after the dissection. Transcriptional profiles of total two samples of polyps and two of non-polyp that pooled from 5 WT and 5 KO mice respectively were analyzed by RNA-seq.

first: Yoichiro

last: Iwakura


title: Analysis of the role of Dectin-1 in the development of intestinal tumor-infiltrating myeloid cells [scRNA-Seq]

summary: To investigate the potential role of Dectin-1 in the development of intestinal tumor-infiltrating myeloid cells, we purified CD11b+ & CD11c+ cells from colorectal polyps of wild-type (WT) or Dectin-1 deficient (Clec7a–/–, KO) mice after azoxymethane (AOM) and 3 cycles of dextran-sodium-sulfate (DSS)-administration for 16 weeks, and compared the differences in the populations of each myeloid cell subset by scRNA-seq.

overall_design: WT and KO mice were admnistrated with AOM (10mg/g) and 3 cycles of 1% DSS for 16 weeks. Colorectal polyps and non-polyp tissues were collected and CD11b+ & CD11c+ myeloid cells were purified by BD FACS Fusion. These cells were then applied for single cell RNA-sequencing.


title: Single cell transcriptomics of fate-restricted HSCs [scRNAseq HSC]

city: Oxford

first: Claus

last: Nerlov

address: John Radcliffe Hospital, University of Oxford

institute: Weatheral Institute of Molecular Medicine

summary: HSC subtypes with distintic lineage restriction have been previously reported. Here we examine the single cell transcriptomics of HSC subtypes with P-restricted, PEM-restricted or multilineage in vivo output.

overall_design: Single cell transplantation of Vwf+ HSCs from mouse bone marrow was performed to generated primary recipients showing lineage-restricted reconstitution over 16 weeks: P-restricted, PEM-restricted and multilineage. Donor-derived HSCs were isolated from recipients' bone marrow for single cell RNA-seq, 2 donors for each cell type

first: Yiran

last: Meng

first: Supat

last: Thongjuea

first: Joana

last: Carrelha

first: Adriana

last: Gambardella

first: Sten

last: Jacobsen


title: Directed Differentiation of Human iPSCs to Functional Ovarian Granulosa-Like Cells via Transcription Factor Overexpression [scRNA-seq]

city: Boston

first: Merrick

middle: Pierson

last: Smela

address: 3 Blackfan Circle

institute: Harvard University

summary: An in vitro model of human ovarian follicles would greatly benefit the study of female reproduction. Ovarian development requires the combination of germ cells and their supporting somatic cells, known as granulosa cells. Whereas efficient protocols exist for generating human primordial germ cell-like cells (hPGCLCs) from human iPSCs, a method of generating granulosa cells has been elusive. Here we report that simultaneous overexpression of two transcription factors (TFs) can direct the differentiation of human iPSCs to granulosa-like cells. We elucidate the regulatory effects of several granulosa-related TFs, and establish that overexpression of NR5A1 and either RUNX1 or RUNX2 is necessary and sufficient to generate granulosa-like cells. Our granulosa-like cells have transcriptomes similar to human fetal ovarian cells, and recapitulate key ovarian phenotypes including follicle formation and steroidogenesis. When aggregated with hPGCLCs, our cells form ovary-like organoids (ovaroids) and support hPGCLC development from the premigratory to the gonadal stage as measured by induction of DAZL expression. This model system will provide unique opportunities for studying human ovarian biology, and may enable the development of therapies for female reproductive health.

overall_design: Single cell RNA-seq of ovarian organoids (ovaroids) formed from iPSC-derived granulosa-like cells and primordial germ cell-like cells.

last: Pierson Smela

first: Christian

last: Kramme

first: Patrick

last: Fortuna

first: Jessica

last: Adams

first: Edward

last: Dong

first: Mutsumi

last: Kobayashi

first: Garyk

last: Brixi

first: Emma

last: Tysinger

first: Richie

last: Kohman

first: Toshi

last: Shioda

first: Pranam

last: Chatterjee

first: George

last: Church


title: Selective Translation of Maternal mRNA by eIF4E1B Controls Oocyte to Embryo Transition

city: Beijing

first: Hailian

last: Zhao

address: 15 Datun Road

institute: Institute of Biophysics, Chinese Academy of Sciences

summary:
To identify mRNAs loaded onto eIF4E1B and eIF4E, LACE-seq was performed using eIF4E1B and eIF4E immunoprecipitated mRNAs from mouse fully grown oocytes
RNA co-precipitated with eIF4E1B and eIF4E differed from the control RNA enriched by the control IgG rabbit serum antibody.

overall_design: According to our previously developed a linear amplification of cDNA ends and sequencing (LACE-seq) methodology to identify RBP targets at or near the single-cell level.we determined the binding sites for eIF4E1B and eIF4E in 100 of fully-grown mouse oocytes. Two biological repeats, labeled as Rep 1 and Rep 2, were generated for each sample.

first: Jing

last: Guo

first: Yuanchao

last: Xue

first: Ge

last: Lin


title: Single cell RNA sequencing of SCLE reveals cell heterogeneiy in skin lesions

city: changsha

first: zheng

last: meiling

state: Hunan

address: jiefang middle street

institute: central south university

summary: SCLE is a clinical subtype of cutaneous lupus erythematosus with psoriatic-like or annular papules with scaly erythematosus, the pathological mechanism of SCLE has been poorly understood. To investigate the immune pathogenesis of SCLE, we performed single-cell RNA sequencing of SCLE skin lesions and integrated with single cell RNA sequencing data of healthy skin. Our results firstly demonstrated that immune cells such as T, B, macrophage/DC and NK cells increased in the skin lesions of SCLE patients. Secondly, through sub-clustering analysis, GO enrichment analysis and cell communication analysis, we revealed that stromal cells such as keratinocytes and fibroblasts in skin lesions of SCLE enhanced chemotactic function for recruiting immune cells. Importantly, we found widespread high expression of interferon-related genes across almost all cell subtypes in SCLE lesions. Additionally, we revealed a general augmentation in lymphocyte subtypes and an increase in inflammatory myeloid cells such as M1 macrophages and pDC in SCLE lesions. In addition to secreting autoreactive antibodies, B cell subsets were verified to assist local immune responses in SCLE lesions. In conclusion, our investigation provides a comprehensive description of skin lesions in SCLE and suggests a range of potential therapeutic targets.

overall_design:
3 skin lesions of SCLE patients were performed single cell RNA sequencing

>>>Submitter states: Raw data not included due to patient privacy concerns.  If needed, those who are interest in our data can connect to our manager whose email address is zhaoming307@csu.edu.cn for his permission to our raw data. <<<

first: Meiling

last: Zheng

first: Zhi

last: Hu

first: Yi

last: Kong

first: Wenhui

last: Zhou

first: Ruifang

last: Wu

first: Ming


title: A comprehensive assessment of a newly designed non-exonic SNP-based NGS panel for HRD detection

city: Shenyang

first: Hongyan

last: Qi

state: Liaoning

address: No.120 Dongling Road, Shenhe District

department: College of Horticulture

institute: Shenyang Agricultural University

summary: Ovarian cancer is a global problem, is typically diagnosed at a late stage and has no effective screening strategy. Platinum-based chemotherapy or Poly(ADP-ribose) polymerase inhibitors (PARPis) treatment are most frequently applied for ovarian cancer patients who are inoperable and in the advanced stage. The recognition of homologous recombination deficiency (HRD) as a biomarker to predict the effect of Platinum-based or PARPis treatment. WGS and WES can detect tumor HRD status but have several disadvantages which restrict their clinical application. My choice HRD CDx and Foundation Focus CDx are approved by FDA for HRD detection, however, whether they are applicable to the Chinese population or not is unknown. In this study, we created an SNP-based Tg-NGS panel to fill in gaps in Chinese patients’ HRD screening. Our results showed that the panel is cost and time-saving compared with WGS, but equivalent with SNP microarray on CNV and HRD detection. In summary, this newly developed kit is promising in clinical application to guide ovarian cancer and even other cancer types therapy.

overall_design: 27 Ovarian cancer samples were tested by OncoScan® CNV FFPE Arrays to detect whole genome copy number variation.

first: Jinxiang

first: Bing

last: Wei

first: Cai

last: Jiang

first: He

last: Zhang

first: Mingye

first: Taoran

last: Cheng

first: Jun

last: Li

first: Zhizhong

last: Wang

first: Lijun

last: Deng

first: Li

first: Qingxin

last: Xia

first: Jie

last: Ma


title: Presence of Ovarian Stromal Aberrations after Cessation of Testosterone Therapy in a Transgender Mouse Model

city: Ann Arbor

first: Hadrian

last: Kinnear

state: MI

address: 1101 Beal Avenue

department: Biomedical Engineering

institute: University of Michigan

summary: Some transmasculine individuals may be interested in pausing gender-affirming testosterone (T) therapy and carrying a pregnancy. The ovarian impact of taking and pausing T is not completely understood. The objective of this study was to utilize a mouse model mimicking transmasculine T therapy to characterize the ovarian dynamics following T cessation. We injected postpubertal 9–10-week-old female C57BL/6N mice once weekly with 0.9 mg of T enanthate or a vehicle control for six weeks. All T-treated mice stopped cycling and demonstrated persistent diestrus within one week of starting T therapy, while control mice cycled regularly. After 6 weeks of T therapy, one group of T-treated mice and age-matched vehicle-treated diestrus controls were sacrificed. Another group of T-treated mice were maintained after stopping T therapy and sacrificed in diestrus four cycles after the resumption of cyclicity along with age-matched vehicle-treated controls. Ovarian histological analysis revealed stromal changes with clusters of large round cells in the post T group as compared to both age-matched controls and mice at six weeks on T. These clusters exhibited periodic acid-Schiff staining, which has been previously reported in multinucleated macrophages in aging mouse ovaries. Notably, many of these cells also demonstrated positive staining for macrophage markers CD68 and CD11b. Ovarian RNA sequencing found upregulation of immune pathways post T as compared to age-matched controls and ovaries at six weeks on T. Although functional significance remains unknown, further attention to the ovarian stroma may be relevant for transmasculine people interested in pausing T to carry a pregnancy.

overall_design: 16 ovarian samples analyzed. 4 biological replicates per group. Groups: On T, Control for On T, Post T, Control for Post T. C57BL/6NHsd female mice (Envigo) either started testosterone (weekly subcutaneous injection of 0.9 mg testosterone enanthate) at 9-10 weeks old or received control sesame oil only injections. At six weeks on T, one cohort was sacrificed ("On T") and compared to parallel age-matched controls ("Control for On T" or "Control OT"). In a separate cohort, testosterone was stopped after 6 weeks and allowed to washout. These mice were followed until resumption of estrous cyclicity and sacrificed after 4 estrous cycles (“Post T”), with parallel age-matched controls (“Control for Post T” or “Control PT”). All mice were sacrificed in diestrus and ovaries were collected for further analysis.

first: Prianka

middle: H

last: Hashim

first: Cynthia

last: Dela Cruz

first: Faith

last: Chang

first: Gillian

last: Rubenstein

first: Likitha

last: Nimmagadda

first: Venkateswaran

last: Ramamoorthi Elangovan

first: Andrea

last: Jones

first: Margaret

middle: A

last: Brunette

first: D

last: Hannum

middle: Z

first: Vasantha

last: Padmanabhan

first: Molly

last: Moravek

first: Ariella

last: Shikanov


title: An epigenetic switch triggers alternative telomere lengthening and cellular immortalization in ATRX deficient cells

city: Berkeley

first: Dirk

last: Hockemeyer

address: Li Ka Shing Center

department: MCB

institute: UC Berkeley

summary: Alternative Lengthening of Telomeres (ALT) is an aberrant DNA recombination pathway which grants replicative immortality to approximately 10% of all cancers. Despite this high prevalence of ALT in cancer, the mechanism and genetics by which cells activate this pathway remain incompletely understood. A major challenge in dissecting the events that initiate ALT is the extremely low frequency of ALT induction in human cell systems. Guided by the genetic lesions that have been associated with ALT from cancer sequencing studies, we genetically engineered primary human pluripotent stem cells to deterministically induce ALT upon differentiation. Using this genetically defined system, we demonstrate that disruption of the p53 and Rb pathways in combination with ATRX loss-of-function is sufficient to induce all hallmarks of ALT and results in functional immortalization in a cell type-specific manner. We further demonstrate that ALT can be induced in the presence of telomerase, is neither dependent on telomere shortening nor crisis, but is rather driven by continuous telomere instability triggered by the induction of differentiation in ATRX-deficient stem cells.

overall_design: Micro-C analysis in human fibroblasts derived from ATRX+/+ or ATRX-/- hESCs.

first: Timothy

last: Turkalo

first: Antonio

last: Maffia

first: Samuel

middle: G

last: Regalado

first: Johannes

last: Schabort

first: Mital

last: Bhakta

first: Marco

last: Blanchette

first: Diana

last: Spierings

first: Peter

last: Lansdorp


title: 9 human epithelial cell transcriptome sequencing analysis

city: JInan

first: Mengmeng

last: Liu

address: Wenhuaxi Road

institute: Shandong University

summary: We report the study of the mechanism of action of Porphyromonas gingivalis on human oral epithelial cells based on high-throughput sequencing technology. By acting Porphyromonas gingivalis and its metabolites on human oral epithelial cells separately, the mechanism of Porphyromonas gingivalis evading immune surveillance and causing local and deep tissue diffusion to induce systemic diseases was studied. This study provides a framework for studying the pathogenic mechanism of Porphyromonas gingivalis.

overall_design: After 6h by P. gingivalis infection, the mRNA of human oral epithelial cell was extracted.

first: LIU

last: MENGMENG


title: Leukocytes methylome of individuals from leprosy endemic area

city: Belo Horizonte

first: Ana Maria

last: Caetano Faria

state: Minas Gerais

address: Av. Antônio Carlos, 6627, Pampulha

department: Bioquímica e Imunologia

institute: Universidade Federal de Minas Gerais

summary: Inflammaging is the name given to this chronic and asymptomatic inflammatory state generated by the aging process and by chronic and infectious diseases. Chronic diseases can alter the epigenetic profile of tissues leading to an increased epigenetic aging and some of the differentially methylated genes can be used to characterize the disease and as disease biomarkers. Leprosy is an infection caused by Mycobacterium leprae and can be lifelong, exposing the individual to a low-grade inflammation environment.  In this study, we evaluated the inflammatory profile in 35 individuals from a leprosy endemic area from Brazil by cytokine analysis with a luminex assay. In adition, we investigated the leucocytes genome-wide DNA methylation profile using the Infinium MethylationEPIC BeadChip array. A total number of 31 CpGs were significantly methylated, between cases and controls, which belonged to 8 genes potentially peripherally perturbed in the pathogenesis of the disease. Affected individuals from endemic area were epigenetically aged in relation to control samples and interesting control samples from endemic area were aged in relation to unaffected control samples from non-endemic area. In conclusion, leprosy showed a deregulated methylation profile in comparison with control samples. The epigenetic analysis provided valuable clues for further investigations in understanding peripherical blood leprosy alterations and the use of these genes as biomarkers.

overall_design: Illumina Infinium Methylation EPIC BeadChip array profiling performed on  individuals from Leprosy endemic area

last: Durso

first: G

last: Silveira-Nunes

last: Camatta

first: M

last: Coelho

first: L

last: Ventura

last: Nascimento

first: F

last: Caixeta

first: T

middle: U

last: Maioli

first: C

last: Sala

last: Bacalini

last: Nardini

last: Franceschi

first: A

last: Faria


title: Identification of the key epigenetic determinants of chondrocyte aging in humans (Single cell-seq)

city: Los Angeles

first: Denis

last: Evseenko

address: 1450 Biggy St

department: Orthopaedic Surgery

institute: University of Southern  California

summary: Articular chondrocytes undergo functional changes and their regenerative potential declines with age. Although the molecular mechanisms guiding articular cartilage aging is poorly understood, DNA methylation is known to play a mechanistic role in aging. However, our understanding of DNA methylation in chondrocyte development across human ontogeny is limited. To better understand DNA methylome changes, methylation profiling was performed in human chondrocytes. This study reveals association between methylation of specific CpG sites and chondrocyte age. We also determined the putative binding targets of STAT3, a key age-patterned TF in fetal chondrocytes and genetic ablation of STAT3 induced a global genomic hypermethylation. Moreover, an epigenetic clock built for adult human chondrocytes revealed that exposure of aged adult human chondrocytes to STAT3 agonist, decreased epigenetic age. Taken together, this work will serve as a foundation to understand development and aging of chondrocytes with a new perspective for development of rejuvenation agents for synovial joints.

overall_design: Single-cell mRNA sequencing for human osteoarthritic chondrocytes using 10x Genomics

first: Ben

last: Van Handel

first: Arijita

last: Sarkar


title: Effect of Nrf2 deletion on developmental lung transcriptomics in mice

city: RTP

first: NIEHS

last: Microarray Core

state: NC

address: 111 T.W. Alexander Drive

department: DIR

institute: NIEHS

summary:
Background: NRF2 is an essential cytoprotective transcription factor inducing antioxidant response element (ARE)-bearing genes. However, association of NRF2 with lung development has not been examined. Human lungs are not fully developed until 2-3 years of and they are fully matured at about 8 years. Murine lungs at birth are immature (at saccular stage of lung development) and have been used to study developmental lung disorders.
Methods: To investigate (1) the transcriptome changes during lung development and (2) the role of NRF2 in lung development and maturation in mice, lungs were harvested from Nrf2-deficient (Nrf2-/-) and wild-type (Nrf2+/+) mouse embryos, neonates and adults.  Microarray and pathway analysis determined NRF2-directed mechanisms underlying lung development and maturation.
Results: Nrf2 mRNA expression was peack at embryonic days E17.5-E18.5 (immediately before birth) probably to increase antioxidant apparatus to prepare against high O2 environment after birth. The pseudoglandular phase lungs (E13-E15) are undergoing vigorous cell proliferation under the control of high-fidelity DNA damage repair system. Fetal lungs (E13.5-E17.5) are lack in immune system, xenobiotic metabolism, and tissue damage genes. After birth at postnatal day 1 (PND1), lung cell division is quiescent but transporters and lipid metabolism are activated. When lung enters alveolar phase (PND4), cell proliferation is resumed.  Mature lungs (PND14-P42) have heightened networks of host defense systems (immunity, antioxidants) and cellular injury and abnormality (e.g., glucose metabolism disorder). Nrf2 deletion in fetal lung (E13.5-E17.5) altered developmental, immunity, and metabolism genes, and it may have affected lung branching. Nrf2 deletion affected lung transcriptome changes the most at E17.5 when Nrf2 message level is maximum (E17.5-E18.5). Nrf2 deletion in newborn lung (PND0) decreased cell cycle progress and DNA damage repair. Nrf2 deletion in neonatal lung (PND1-4) enhanced tissue injury/cell death and inhibited developmental cell differentiation. Nrf2 deletion in matured mouse lung (PND42) affected not only antioxidant pathway but also immune responses and connective tissue cell migrations.
Conclusion: Overall, NRF2 plays multiple roles in underdeveloped lungs and associated with lung morphogenesis, immunity, cell cycle progress, tissue differentiation and metabolism as well as cellular defense. Results provide putative molecular mechanisms of NRF2-directed lung morphogenesis and maturation.

overall_design: PARALLEL study design with 66 samples comparing 22 groups  of different age (E13.5, E15.5, E17.5, E18.5, PND0, PND1, PND2, PND3, PND4, PND14, PND42) and genotype (Nrf2+/+ or WT, Nrf2-/- or KO): 11 groups Nrf2+/+ WT from E13.5 to PND42, 11 groups Nrf2-/- KO from E13.5 to PND42. Biological replicates: 3 per group

first: Steven

last: Kleeberger

first: Hye-Youn

last: Cho


title: XRN1 knockdown stimulate innate immune reponse in murine melanoma cells

city: Singapore

first: Ying

last: Li

state: --- Select a state ---

address: 14 Medical Dr, Singapore

country: Singapore

institute: Cancer Science Institute of Singapore

summary: Despite the remarkable achievement of immune checkpoint blockade (ICB) therapy, the response rate is relatively low and only a subset of patients can benefit from the treatment. We hypothesize that targeting RNA decay machinery may lead to accumulation of aberrantRNA, triggering interferon (IFN) signaling and sensitizing tumor cells to immunotherapy. With this in mind, we identified an RNA exoribonuclease, XRN1 as a potential target. Silencing of XRN1 suppressed tumor growth in syngeneic immunocompetent mice and potentiated immunotherapy, while silencing of XRN1 alone did not affect tumor growth in immune deficient mice. Mechanistically, XRN1 depletion activated interferon signaling and viral defense pathway; both pathways play determinant roles in regulating immune evasion. We identified aberrant-RNA sensing signaling proteins (RIG-I/MAVS and PKR) in mediating the expression of IFN genes, as depletion of each of them blunted the elevation of anti-viral/IFN signaling in Xrn1 silenced cells. Analysis of pan-cancer CRISPR screening data indicated that IFN signaling triggered by Xrn1 silencing is a common phenomenon, suggesting that the effect of Xrn1 silencing may be extend to multiple types of cancers.

overall_design: XRN1 was knockdown in murine melanoma cell B16/F10 and D4M.3A using multiple techniques including siRNA, shRNA and sgRNA. Five sets of total RNA were extracted; NSG was perfomed to measure the global change of gene expression. The gene expression profiles of XRN1 silenced ones were compared with respective controls (D4M.3A-shXrn1 vs D4M.4A-shCtrl, D4M.3A-sgXrn1 vs D4M.3A-Cas9, B16/F10-siXrn1 vs B16/F10-siCtrl, B16/F10-shXrn1 vs B16/F10-shCtrl, B16/F10-sgXrn1 vs B16/F10-Cas9).

first: Xue-Bin

last: Ran

first: Ling-Wen

last: Ding

first: Henry

last: Yang


title: XRN1 knockdown in tumor cells stimulates immune cell infiltration

summary: Despite the remarkable achievement of immune checkpoint blockade (ICB) therapy, the response rate is relatively low and only a subset of patients can benefit from the treatment. We hypothesize that targeting RNA decay machinery may lead to accumulation of aberrantRNA, triggering interferon (IFN) signaling and sensitizing tumor cells to immunotherapy. With this in mind, we identified an RNA exoribonuclease, XRN1 as a potential target. Silencing of XRN1 suppressed tumor growth in syngeneic immunocompetent mice and potentiated immunotherapy, while silencing of XRN1 alone did not affect tumor growth in immune deficient mice. Mechanistically, XRN1 depletion activated interferon signaling and viral defense pathway; both pathways play determinant roles in regulating immune evasion. In murine tumors engrafted on immmunocompetent mice, XRN1 depletion significantly enhanced immune cell infiltration in solid tumors especially in combinatory with PD-1 blockade. We identified aberrant-RNA sensing signaling proteins (RIG-I/MAVS and PKR) in mediating the expression of IFN genes, as depletion of each of them blunted the elevation of anti-viral/IFN signaling in Xrn1 silenced cells. Analysis of pan-cancer CRISPR screening data indicated that IFN signaling triggered by Xrn1 silencing is a common phenomenon, suggesting that the effect of Xrn1 silencing may be extend to multiple types of cancers.

overall_design: XRN1 was knocked out in murine melanoma cell B16/F10 using sgRNA. The control and XRN1 knockout cells were inoculated into C57BL/6 mice and treated with/without GVAX plus PD-1 antibody treatment. Three largest tumors of each group (four groups and 12 samples in total) were chosen for RNA seq analysis.

first: Qiao-Yang

last: Sun


title: Identification of the key epigenetic determinants of chondrocyte aging in humans (Cut&Run)

overall_design: Genome binding/occupancy profiling for STAT3 by high throughput sequencing in human fetal, adult and osteoarthritic chondrocytes


title: The effect of K458R mutation of HNF4A on HCC

status: Public on Feb 20 2023

city: Shanghai

first: xin

last: zhang

address: 415 Fengyang Road

institute: Changzheng hospital

summary: To investigate the inhibitory effect of K458R mutation of HNF4A on HCC, we established Huh-7 xenografts treated with Ad-GFP, Ad-HNF4A or Ad-K458R. We then performed gene expression profiling analysis using data obtained from RNA-seq of three groups of  Huh-7 xenografts treated with adenovirus.

overall_design: Comparative gene expression profiling analysis of RNA-seq data for Huh-7 xenografts treated with Ad-GFP, Ad-HNF4A or Ad-K458R.

first: Fang

last: Liu

last: Jiang

first: Mengchao

last: Xiao


title: Identification of the key epigenetic determinants of chondrocyte aging in humans (ATAC-seq)

overall_design: ATAC sequencing for human fetal chondrocytes


title: Novel RXR agonists differentially regulate gene transcription in mammary tumors of MMTV-neu mice

city: East Lansing

first: Lyndsey

last: Reich

state: Michigan

address: 1355 Bogue St.

department: Pharmacology & Toxicology

institute: Michigan State University

summary: RXR agonists, which activate the RXR nuclear receptor, are effective in multiple preclinical cancer models for both treatment and prevention. While RXR is the target of these compounds, the downstream effects on gene expression differs between compounds. To elucidate the effects of the novel RXR agonist MSU 42011 on the transcriptome in tumors of MMTV-Neu mice, we performed RNA sequencing. For comparative analysis, RNA sequencing was also performed on tumors treated with the FDA approved RXR agonist bexarotene. Female MMTV-Neu mice with established mammary tumors 4 mm in diameter were fed control diet, bexarotene (100 mg/kg in diet), or MSU 42011 (100 mg/kg in diet) for 10 days. Both treatments differentially regulated cancer-relevant gene sets, such as focal adhesion, extracellular matrix, and immune pathways. Many of the top genes differentially regulated by RXR agonists are positively associated with survival in breast cancer patients. While MSU 42011 and bexarotene act on many common pathways, these experiments coupled with gene expression analysis of tumors treated with another novel RXR agonist V-125 highlight the differences in regulation of gene expression between these compounds of the same class. Exploration of these unique effects on gene transcription may lead to an increased understanding of the complex biology behind RXR agonists, and how the activities of this diverse class of compounds can be utilized to treat cancer.

overall_design: Comparative gene expression profiling analysis of RNA-seq data for murine tumors treated with different RXR agonists

first: Ana

middle: S

last: Leal

first: Carl

last: Wagner

first: Edmund

last: Ellsworth

first: Karen

middle: T

last: Liby


title: fate-restricted HSCs

first: Claus

last: Nerlov

department: MRC Molecular Haematology Unit

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

overall_design: Refer to individual Series


title: Transcriptome, Small RNA, and Degradome Sequencing Reveals the Roles of MicroRNAs in Response to High Night Temperature Stress at the Filling Stage of Rice

city: nanchang

first: zhao

middle: hai

last: wang

state: jiangxi

address: zhimin dadao 1101

institute: jiangxi agricultural university

summary: we utilized transcriptome sequencing to identify differentially expressed genes in rice heat-tolerant line and heat-sensitive line under high night temperature stress .

overall_design: the treatment and control of the heat-sensitive and -tolerant lines of near-isogenic lines with significant differences in heat tolerance at filling stage

first: Jiangmin

last: Fan

first: Hongyu

last: Zhang

first: Yan

last: Shi

first: Yuewu

first: Yuxiang

last: He

first: Qiang

last: Wang

first: Siyi

first: Youmin

last: Yao

first: Jianglin

last: Liao

first: Yingjin

last: Huang

first: Zhaohai


title: Gene expression profile of Vibrio cholerae N16961 grown in various conditions of culture

city: Paris

first: Rachel

last: Legendre

address: 28, rue du docteur Roux

department: Research and Resource Center for Scientific Informatics

institute: Institut Pasteur

summary:
To investigate the effect of conditions of culture on gene expression in Vibrio cholerae N16961
We then performed gene expression profiling analysis using data obtained from RNA-seq of 4 conditions of culture in biological duplicate

sample_organism: Vibrio cholerae O1 biovar El Tor str. N16961

overall_design: Comparative gene expression profiling analysis of RNA-seq data for  Vibrio cholerae N16961 grown in four conditions of culture

first: Evelyne

last: Krin

first: Odile

last: Sismeiro

first: Hugo

last: Varet

first: Zeynep

last: Baharoglu

first: Jean-Yves

last: Coppée

first: Didier

last: Mazel


title: Type I Interferon Signaling via the EGR2 Transcriptional Regulator Potentiates CAR T cell-intrinsic Dysfunction (RNA-Seq)

city: Philadelphia

first: Inyoung

last: Jung

state: PA

address: SPE, 9-304, 3400 Civic Center Blvd, Bldg. 421

institute: University of Pennsylvania

summary: Chimeric antigen receptor (CAR) T-cell therapy has achieved remarkable success in the treatment of hematopoietic cancers, but resistance is common, and efficacy is limited in solid tumors. We demonstrate that CAR T-cells autonomously propagate epigenetically-programmed type I interferon signaling through chronic stimulation or antigen-independent tonic activation, which progressively hampers antitumor effector function. EGR2 transcriptional regulator knockoutnot only blocks this type I interferon-mediated inhibitory program, but also independently expands early memory CAR T-cells with improved efficacy against liquid and solid tumors. The protective effect of EGR2 deletion in CAR T-cells against chronic antigen-induced dysfunction can be overridden by interferon-β exposure, suggesting that EGR2 ablation suppresses CAR T-cell dysfunction through inhibition of type I interferon signaling. Finally, enrichment of an EGR2 gene signature is a clinical biomarker for type I interferon-associated CAR T-cell failure and shorter overall patient survival. These findings conceptually connect prolonged CAR T-cell activation with deleterious immunoinflammatory signaling and point to an EGR2-type I interferon axis as a therapeutically amenable biologic system.

overall_design: AAVS1 and EGR2 knockout PSMA CAR T-cells produced from two different healthy subjects were isolated from the in vitro “stress test” after multiple consecutive rounds of antigen stimulation. Single-cell multiome-seq libraries were prepared using Chromium Single Cell Multiome ATAC and Gene Expression Reagent Kits V1 (10X Genomics).

first: In-Young

first: Robert

last: Bartoszek

first: Andrew

last: Rech

first: Sierra

last: McDonald

first: Soon-Keat

last: Ooi

first: Erik

last: Williams

first: Caitlin

last: Hopkins

first: Vivek

last: Narayan

first: Naomi

middle: B

last: Haas

first: Noelle

middle: V

last: Frey

first: Elizabeth

middle: O

last: Hexner

first: Donald

last: Siegel

first: Gabriela

last: Plesa

first: David

last: Porter

first: Adrian

last: Cantu

first: John

last: Everett

first: Sonia

last: Guedan

first: Shelley

last: Berger

first: Frederic

middle: D

last: Bushman

first: Joseph

last: Fraietta


title: Genome-wide CRISPR/Cas9 Screens Reveal Shared and Bespoke Mechanisms of Resistance to SHP2 inhibition [CRISPR mini screen]

city: New York

first: Igor

last: Dolgalev

state: New York

address: 550 1st Ave

institute: NYU Grossman School of Medicine

summary: CRISPR/Cas9 screens identified unexpected hits in human AML cell lines whose loss of function causes resistance to SHP2 inhibition

overall_design: CRISPR mini-screens were conducted with 14 cancer cell lines with a focused CRISPR library, to identify common resistant hits to SHP099

first: Wei

last: Wei

first: Benjamin

last: Neel


title: mRNA expression profiles of 223 cancer cell lines including newly established ones

city: Tokyo

first: Masayuki

last: Komatsu

address: 5-1-1, Tsukiji, Chuo-ku

institute: National Cancer Center Research Institute

summary:
Establishment and molecular characterization of 239 peritoneally-metastatic cancer cell lines from 170 patients’ ascites in 11 kinds of cancers mainly consisted of gastric, pancreatic, and ovarian cancer.
We performed comparative transcriptome analyses using microarrays between our established cancer cell lines and cell-bank derived cancer cell lines

overall_design: 223 cancer cell lines

first: Fumiko

last: Chiwaki

first: Rie

last: Komatsuzaki

first: Hiroki

last: Sasaki


title: Type I Interferon Signaling via the EGR2 Transcriptional Regulator Potentiates CAR T cell-intrinsic Dysfunction

first: Inyoung

last: Jung


title: Type I Interferon Signaling via the EGR2 Transcriptional Regulator Potentiates CAR T cell-intrinsic Dysfunction (ATAC-Seq)

first: In-Young

first: Robert

last: Bartoszek

first: Andrew

middle: J

last: Rech

first: Sierra

last: McDonald

first: Soon-Keat

last: Ooi

first: Erik

last: Williams

first: Caitlin

last: Hopkins

first: Vivek

last: Narayan

first: Naomi

last: Haas

first: Noelle

last: Frey

first: Elizabeth

last: Hexner

first: Donald

middle: L

last: Siegel

middle: K


title: Genome-wide CRISPR/Cas9 Screens Reveal Shared and Bespoke Mechanisms of Resistance to SHP2 inhibition [CRISPR genomic screen]

first: Igor

last: Dolgalev

overall_design: CRISPR/Cas9 screens in two human AML cell lines (MOLM13 and MV4-11) to identify resistant hits to SHP2 inhibitor (SHP099)

first: Wei

last: Wei

first: Benjamin

last: Neel


title: An mRNA processing pathway suppresses metastasis by governing translational control from the nucleus [Quant-seq]

city: San Francisco

first: Hani

last: Goodarzi

state: CA

department: Biochemistry and Biophysics

institute: UCSF

summary: Cancer cells often co-opt post-transcriptional regulatory mechanisms to achieve pathologic expression of gene networks that drive metastasis. Translational control is a major regulatory hub in oncogenesis, however its effects on cancer progression remain poorly understood. To address this, we used ribosome profiling to compare genome-wide translation efficiencies of poorly and highly metastatic breast cancer cells and patient-derived xenografts. We developed novel regression-based methods to analyze ribosome profiling and alternative polyadenylation data, and identified HNRNPC as a translational controller of a specific mRNA regulon. Mechanistically, HNRNPC, in concert with PABPC4, binds near to poly(A) signals, thereby governing the alternative polyadenylation of a set of mRNAs. We found that HNRNPC and PABPC4 are downregulated in highly metastatic cells, which causes HNRNPC-bound mRNAs to undergo 3’ UTR lengthening and subsequently, translational repression. We showed that modulating HNRNPC expression impacts the metastatic capacity of breast cancer cells in xenograft mouse models. We also found that a small molecule, previously shown to induce a distal-to-proximal poly(A) site switching, counteracts the HNRNPC-PABPC4 driven deregulation of alternative polyadenylation and decreases the metastatic lung colonization by breast cancer cells in vivo.

overall_design: Comparing alternative polyadenylation landscapes in highly and poorly metastatic breast cancer cells

first: Albertas

last: Navickas

first: Hosseinali

last: Asgharian

first: Juliane

last: Winkler

first: Lisa

last: Fish

first: Kristle

last: Garcia

first: Daniel

last: Markett

first: Martin

last: Dodel

first: Bruce

last: Culbertson

first: Sohit

last: Miglani

first: Tanvi

last: Joshi

first: Phi

last: Nguyen

first: Steven

last: Zhang

first: Nicholas

last: Stevers

first: Hun-Way

last: Hwang

first: Faraz

last: Mardakheh

first: Andrei

last: Goga


title: An mRNA processing pathway suppresses metastasis by governing translational control from the nucleus [Ribo-seq, RNA-seq]

first: Hani

last: Goodarzi

overall_design: Comparison of translation efficiencies in highly and poorly metastatic breast cancer cell lines


title: Aberrant expression of GOLM1 protects ALK+ anaplastic large cell lymphoma from apoptosis by enhancing BCL-XL stability

city: shanghai

first: zhenguo

last: zi

state: shanghai

address: Building 5, 100 Banxia Road, Pudong New Area, Shanghai

institute: Shanghai Jiao Tong university

summary: GOLM1 suppresses ALCL apoptosis in ALCL

overall_design: We then performed gene expression profiling analysis using data obtained from RNA-seq of SUP-M2 cell line performing GOLM1 knockout compared with control

first: Zhenguo

last: Zi

first: Fang

last: Wei

first: Xiaojing

last: Ma

first: Qiliang

last: Cai


title: 3D ECM-rich environment sustains the identity of naïve human iPSCs

city: Padua

first: Alessia

last: Gesualdo

address: Via Gradenigo, 6a

department: Industrial Engineering

country: Italy

institute: University of Padua

summary: The establishment of in vitro naïve human pluripotent stem cell cultures opened new perspectives for the study of early events in human development. The role of several transcription factors and signalling pathways during maintenance of human naïve pluripotency have been characterized. However, little is known about the role exerted by the extracellular matrix (ECM) and its three-dimensional (3D) organization. Here, using an unbiased and integrated approach combining transcriptional, proteomic and secretome analyses, we found that naïve, but not primed, hiPSC colonies are characterized by a self-organized ECM-rich microenvironment. Based on this, we developed a 3D culture system that supports robust long-term feeder-free self-renewal of naïve hiPSCs, and also allows direct and timely developmental morphogenesis simply by modulating the signalling environment. Our study opens new perspectives for future applications of naïve hiPSCs to study critical stages of human development in 3D starting from a single cell.

overall_design: Bulk RNA-seq. Comparison of the transcriptomic profile of naïve hiPSCs cultured in 3D Matrigel, primed hiPSCs in 3D Matrigel, primed hiPSCs in 2D, and naïve hiPSCs cultured in 3D Matrigel undergoing priming. Naïve 3D hiPSCs and Primed 2D hiPSCs were harvested at day 4 of culture, primed 3D hiPSCs were harvested at day 5 of culture, while cells in priming condition were harvested at day 2, 4, 6, 8 and 10 of culture. Quadruplicates were collected for every condition and total RNA extracted with Qiagen RNeasy Mini Kit.

first: Elisa

last: Cesare

first: Anna

last: Urciuolo

first: Hannah

last: Stuart

first: Erika

last: Torchio

first: Cecilia

last: Laterza

first: Onelia

last: Gagliano

first: Sebastian

last: Martewicz

first: Meihua

last: Cui

last: Manfredi

first: Lucio

last: Di Filippo

first: Patrizia

last: Sabatelli

first: Stefano

last: Squarzoni

first: Irene

last: Zorzan

first: Riccardo

middle: M

last: Betto

first: Graziano

last: Martello

first: Davide

last: Cacchiarelli

first: Camilla

last: Luni

first: Nicola

last: Elvassore


title: Genome-wide CRISPR/Cas9 Screens Reveal Shared and Bespoke Mechanisms of Resistance to SHP2 Inhibition [RNA-seq]

first: Igor

last: Dolgalev

summary: CRISPR/Cas9 screens identified unexpected hits in human AML cell lines whose loss of function causes resistance to SHP2 inhibition.

overall_design: Transcriptomic analysis of INPPL1, or MAP4K5 KO compared with parental MOLM13 cells either under SHP099 treatment or Ctrl (DMSO) to identify key pathways causing resistance.

first: Wei

last: Wei

first: Benjamin

last: Neel


title: HIV-1 integration in microglia

city: Heidelberg

first: Carl

last: Herrmann

address: INF 267

department: Medical Faculty

country: Germany

institute: University Heidelberg


title: Differential gene expression in Drosophila larval brain due to mutation in the Beadex gene

city: Bangalore

first: Genotypic

last: technology

state: Karnataka

address: 259, Apoorva 4th cross,80 feet Road,RMV 2ND STAGE

institute: Genotypic Technology

summary: The appropriate growth of the neurons, accurate organization of their synapses, and successful neurotransmission are indispensable for sensorimotor activities. These processes are highly dynamic and tightly regulated. Extensive genetic, molecular, physiological, and behavioural studies have identified many molecular players and investigated their roles in various neuromuscular processes. In this paper we show that Beadex (Bx), the Drosophila LIM only (LMO) protein, governs the growth of larval neuromuscular junctions (NMJs) and neuronal activities. The Bx mutant, Bx7, and the RNAi-mediated neuronal-specific knockdown of Bx show drastically reduced synaptic span of the NMJs, an increased spontaneous neuronal firing with altered motor patterns in the CPGs. Microarray studies identified multiple targets of Bx that are involved in different cellular and molecular pathways, including those associated with the cytoskeleton and mitochondria, that could be responsible for the observed neuromuscular defects. With genetic interaction studies, we further show that Highwire (Hiw), a negative regulator of synaptic growth at the NMJs, negatively regulates Bx, as the latter’s deficiency was able to rescue the phenotype of the Hiw dominant negative mutant, HiwDN.

overall_design: Agilent one-color experiment,Organism: Drosophila melanogaster, Agilent Microarray Gene Expression Drosophila 4x 44k Arrays AMADID: 18972

first: Subhash

last: Kairamkonda

first: Upendra

last: Nongthomba


title: Human germline biallelic complete NFAT1 deficiency causes the triad of joint contractures, osteochondromas, and susceptibility to B cell malignancy [Single]

city: Vancouver

first: Stuart

middle: E

last: Turvey

state: BC

address: 938 W 28th Ave

institute: BC Children's Hospital Research Institute

summary: We isolated peripheral blood mononuclear cells from whole blood from an NFAT1 deficient patient and 5 healthy controls. Cells were either treated with PMA (50ng/mL) + 1uM Ionomycin for 4 hours, or left untreated. Cells were then isolated in nanowells, and incubated with single mRNA-capture beads. mRNA from these beads were used for library preparation and sequenced. Raw counts were used for clustering analysis and differential expression. This analysis pointed to defects in NFAT1 deficient patient's B-cells and T-cells that could be contributing the observed B-cell malignancy

overall_design: Single cell transcriptome profiling of NFAT1 deficient patient PBMCs against 5 healthy controls (3 family members and 2 age-matched sex-matched healthy controls), with or without stimulations (4hrs 50ng/mL PMA + 1uM Ionomycin)

first: Mehul

last: Sharma

first: Maggie

middle: P

last: Fu

first: Henry

middle: Y

last: Lu

first: Ashish


title: Human germline biallelic complete NFAT1 deficiency causes the triad of joint contractures, osteochondromas, and susceptibility to B cell malignancy [Bulk]

summary: We isolated chondrocytes from an NFAT1 deficient patients osteochondromas surgically removed from the promixal tibia. The cells were either infected with empty vector (labeled "patient") or WT-NFATC2 (labeled "rescue"). We then conducted differential expression, and gene-set enrichment analysis and determined that inflammatory and cell proliferation signals were higher in "patient" chondrocytes

overall_design: Transcriptome profiling of Empty Vector transduced and WT-NFATC2 transduced patient chondrocytes in technical triplicate, with or without stimulations (4hrs 20ng/mL IL-1b, 50ng/mL PMA + 1uM Ionomycin)

middle: A


title: Human germline biallelic complete NFAT1 deficiency causes the triad of joint contractures, osteochondromas, and susceptibility to B cell malignancy


title: Profiling non-human primate exosomal RNA to understand the legacy of early life stress

first: Brian

middle: George

last: Dias

address: 4650 Sunset Blvd

department: Division of Endocrinology

institute: Children's Hospital Los Angeles

summary: Validation of the etection of the RNA content in plasma exosomes  of rhesus macaques.

overall_design: Total RNA sequencing

middle: G


title: Transcriptome-wide binding sites of HNRNPC and PABPC4 determined using cross-linking immunoprecipitation (CLIP)

first: Hani

last: Goodarzi

overall_design: Mapping RNA-protein interactions for HNRNPC and PABPC4.

first: Navickas

last: Albertas

first: Asgharian

last: Hosseinali

first: Fish

last: Lisa

first: Goodarzi

last: Hani


title: Translation efficiency changes measured using ribosome footprinting (Ribo-seq) in poorly and highly metastatic cancer cells

overall_design: Comparison of translation efficiencies in highly and poorly metastatic breast cancer cell lines and PDXs

first: Miglani

last: Sohit


title: The role of HNRNPC-PABPC4 on polyA site selection

overall_design: Comparing alternative polyadenylation landscapes in response to double and single knockdowns of HNRNPC and PABPC4.

first: Winkler

last: Juliane

first: Garcia

last: Kristle