title: Histone ChIP-seq from BLaER1 (ENCSR311RXD)

summary:
H3K4me2 ChIP-Seq on BLaER1 cell line after 72 h treatment with 100 nM 17β-estradiol, 10 ng/mL Interleukin-3, 10 ng/mL CSF1.

For data usage terms and conditions, please refer to http://www.genome.gov/27528022 and http://www.genome.gov/Pages/Research/ENCODE/ENCODE_Data_Use_Policy_for_External_Users_03-07-14.pdf


title: Histone ChIP-seq from BLaER1 (ENCSR217SDT)

status: Public on Feb 27 2024

city: Stanford

first: ENCODE

last: DCC

state: CA

address: 300 Pasteur Dr

country: USA

institute: ENCODE DCC

type: Genome binding/occupancy profiling by high throughput sequencing

summary:
H3K27ac ChIP-Seq on BLaER1 cell line after 48 h treatment with 100 nM 17β-estradiol, 10 ng/mL Interleukin-3, 10 ng/mL CSF1.

For data usage terms and conditions, please refer to http://www.genome.gov/27528022 and http://www.genome.gov/Pages/Research/ENCODE/ENCODE_Data_Use_Policy_for_External_Users_03-07-14.pdf


title: TF ChIP-seq from BLaER1 (ENCSR334SSD)

summary:
CEBPA ChIP-Seq on BLaER1 cell line after 9 h treatment with 100 nM 17β-estradiol, 10 ng/mL Interleukin-3, 10 ng/mL CSF1.

For data usage terms and conditions, please refer to http://www.genome.gov/27528022 and http://www.genome.gov/Pages/Research/ENCODE/ENCODE_Data_Use_Policy_for_External_Users_03-07-14.pdf


title: Histone ChIP-seq from BLaER1 (ENCSR239WVI)

summary:
H3K36me3 ChIP-Seq on BLaER1 cell line after 36 h treatment with 100 nM 17β-estradiol, 10 ng/mL Interleukin-3, 10 ng/mL CSF1.

For data usage terms and conditions, please refer to http://www.genome.gov/27528022 and http://www.genome.gov/Pages/Research/ENCODE/ENCODE_Data_Use_Policy_for_External_Users_03-07-14.pdf


title: Histone ChIP-seq from BLaER1 (ENCSR205SJZ)

summary:
H3K4me3 ChIP-Seq on BLaER1 cell line after 120 h treatment with 100 nM 17β-estradiol, 10 ng/mL Interleukin-3, 10 ng/mL CSF1.

For data usage terms and conditions, please refer to http://www.genome.gov/27528022 and http://www.genome.gov/Pages/Research/ENCODE/ENCODE_Data_Use_Policy_for_External_Users_03-07-14.pdf


title: TF ChIP-seq from BLaER1 (ENCSR236DYB)

summary:
CEBPA ChIP-Seq on BLaER1 cell line after 72 h treatment with 100 nM 17β-estradiol, 10 ng/mL Interleukin-3, 10 ng/mL CSF1.

For data usage terms and conditions, please refer to http://www.genome.gov/27528022 and http://www.genome.gov/Pages/Research/ENCODE/ENCODE_Data_Use_Policy_for_External_Users_03-07-14.pdf


title: Histone ChIP-seq from BLaER1 (ENCSR308PVP)

summary:
H3K9me3 ChIP-Seq on untreated BLaER1 cell line.

For data usage terms and conditions, please refer to http://www.genome.gov/27528022 and http://www.genome.gov/Pages/Research/ENCODE/ENCODE_Data_Use_Policy_for_External_Users_03-07-14.pdf


title: Histone ChIP-seq from BLaER1 (ENCSR168QMC)

summary:
H3K9me3 ChIP-Seq on BLaER1 cell line after 9 h treatment with 100 nM 17β-estradiol, 10 ng/mL Interleukin-3, 10 ng/mL CSF1.

For data usage terms and conditions, please refer to http://www.genome.gov/27528022 and http://www.genome.gov/Pages/Research/ENCODE/ENCODE_Data_Use_Policy_for_External_Users_03-07-14.pdf


title: Histone ChIP-seq from BLaER1 (ENCSR029BVT)

summary:
H3K9me3 ChIP-Seq on BLaER1 cell line after 168 h treatment with 100 nM 17β-estradiol, 10 ng/mL Interleukin-3, 10 ng/mL CSF1.

For data usage terms and conditions, please refer to http://www.genome.gov/27528022 and http://www.genome.gov/Pages/Research/ENCODE/ENCODE_Data_Use_Policy_for_External_Users_03-07-14.pdf


title: Histone ChIP-seq from BLaER1 (ENCSR144SOW)

summary:
H4K20me1 ChIP-Seq on BLaER1 cell line after 18 h treatment with 100 nM 17β-estradiol, 10 ng/mL Interleukin-3, 10 ng/mL CSF1.

For data usage terms and conditions, please refer to http://www.genome.gov/27528022 and http://www.genome.gov/Pages/Research/ENCODE/ENCODE_Data_Use_Policy_for_External_Users_03-07-14.pdf


title: Histone ChIP-seq from BLaER1 (ENCSR243UAI)

summary:
H4K20me1 ChIP-Seq on BLaER1 cell line after 120 h treatment with 100 nM 17β-estradiol, 10 ng/mL Interleukin-3, 10 ng/mL CSF1.

For data usage terms and conditions, please refer to http://www.genome.gov/27528022 and http://www.genome.gov/Pages/Research/ENCODE/ENCODE_Data_Use_Policy_for_External_Users_03-07-14.pdf


title: Histone ChIP-seq from BLaER1 (ENCSR218KHF)

summary:
H3K9ac ChIP-Seq on BLaER1 cell line after 12 h treatment with 100 nM 17β-estradiol, 10 ng/mL Interleukin-3, 10 ng/mL CSF1.

For data usage terms and conditions, please refer to http://www.genome.gov/27528022 and http://www.genome.gov/Pages/Research/ENCODE/ENCODE_Data_Use_Policy_for_External_Users_03-07-14.pdf


title: TF ChIP-seq from BLaER1 (ENCSR288MRA)

summary:
CEBPA ChIP-Seq on BLaER1 cell line after 168 h treatment with 100 nM 17β-estradiol, 10 ng/mL Interleukin-3, 10 ng/mL CSF1.

For data usage terms and conditions, please refer to http://www.genome.gov/27528022 and http://www.genome.gov/Pages/Research/ENCODE/ENCODE_Data_Use_Policy_for_External_Users_03-07-14.pdf


title: Histone ChIP-seq from BLaER1 (ENCSR037TSC)

summary:
H3K9ac ChIP-Seq on BLaER1 cell line after 24 h treatment with 100 nM 17β-estradiol, 10 ng/mL Interleukin-3, 10 ng/mL CSF1.

For data usage terms and conditions, please refer to http://www.genome.gov/27528022 and http://www.genome.gov/Pages/Research/ENCODE/ENCODE_Data_Use_Policy_for_External_Users_03-07-14.pdf


title: Histone ChIP-seq from BLaER1 (ENCSR039AHR)

summary:
H3K27ac ChIP-Seq on BLaER1 cell line after 6 h treatment with 100 nM 17β-estradiol, 10 ng/mL Interleukin-3, 10 ng/mL CSF1.

For data usage terms and conditions, please refer to http://www.genome.gov/27528022 and http://www.genome.gov/Pages/Research/ENCODE/ENCODE_Data_Use_Policy_for_External_Users_03-07-14.pdf


title: Histone ChIP-seq from BLaER1 (ENCSR136NZR)

summary:
H3K4me1 ChIP-Seq on BLaER1 cell line after 18 h treatment with 100 nM 17β-estradiol, 10 ng/mL Interleukin-3, 10 ng/mL CSF1.

For data usage terms and conditions, please refer to http://www.genome.gov/27528022 and http://www.genome.gov/Pages/Research/ENCODE/ENCODE_Data_Use_Policy_for_External_Users_03-07-14.pdf


title: Histone ChIP-seq from BLaER1 (ENCSR285NFQ)

summary:
H3K27ac ChIP-Seq on BLaER1 cell line after 36 h treatment with 100 nM 17β-estradiol, 10 ng/mL Interleukin-3, 10 ng/mL CSF1.

For data usage terms and conditions, please refer to http://www.genome.gov/27528022 and http://www.genome.gov/Pages/Research/ENCODE/ENCODE_Data_Use_Policy_for_External_Users_03-07-14.pdf


title: TF ChIP-seq from BLaER1 (ENCSR195PUH)

summary:
CEBPA ChIP-Seq on BLaER1 cell line after 12 h treatment with 100 nM 17β-estradiol, 10 ng/mL Interleukin-3, 10 ng/mL CSF1.

For data usage terms and conditions, please refer to http://www.genome.gov/27528022 and http://www.genome.gov/Pages/Research/ENCODE/ENCODE_Data_Use_Policy_for_External_Users_03-07-14.pdf


title: Histone ChIP-seq from BLaER1 (ENCSR131EHC)

summary:
H3K4me2 ChIP-Seq on BLaER1 cell line after 168 h treatment with 100 nM 17β-estradiol, 10 ng/mL Interleukin-3, 10 ng/mL CSF1.

For data usage terms and conditions, please refer to http://www.genome.gov/27528022 and http://www.genome.gov/Pages/Research/ENCODE/ENCODE_Data_Use_Policy_for_External_Users_03-07-14.pdf


title: Histone ChIP-seq from BLaER1 (ENCSR197KBA)

summary:
H3K27me3 ChIP-Seq on BLaER1 cell line after 72 h treatment with 100 nM 17β-estradiol, 10 ng/mL Interleukin-3, 10 ng/mL CSF1.

For data usage terms and conditions, please refer to http://www.genome.gov/27528022 and http://www.genome.gov/Pages/Research/ENCODE/ENCODE_Data_Use_Policy_for_External_Users_03-07-14.pdf


title: Histone ChIP-seq from BLaER1 (ENCSR010OVI)

summary:
H3K27ac ChIP-Seq on BLaER1 cell line after 72 h treatment with 100 nM 17β-estradiol, 10 ng/mL Interleukin-3, 10 ng/mL CSF1.

For data usage terms and conditions, please refer to http://www.genome.gov/27528022 and http://www.genome.gov/Pages/Research/ENCODE/ENCODE_Data_Use_Policy_for_External_Users_03-07-14.pdf


title: Histone ChIP-seq from BLaER1 (ENCSR006ANF)

summary:
H3K27ac ChIP-Seq on BLaER1 cell line after 12 h treatment with 100 nM 17β-estradiol, 10 ng/mL Interleukin-3, 10 ng/mL CSF1.

For data usage terms and conditions, please refer to http://www.genome.gov/27528022 and http://www.genome.gov/Pages/Research/ENCODE/ENCODE_Data_Use_Policy_for_External_Users_03-07-14.pdf


title: Identification of Foxp1 regulating target genes in renal cells  using ChIP-seq sequencing

city: Camperdown

first: RENHUA

last: SONG

state: NSW

address: Charles Perkins Centre - D17, Level 4 West. The University of Sydney Johns Hopkins Drive

country: Australia

institute: Centenary Institute

summary: To investigate the specific role of Foxp1 in kidney tubular system, we specifically deleted Foxp1 expression in kidney distal nephrons and collecting ducts. We examined the effects of Foxp1 on IC differentiation and urine acidification. Chip-seq was used to identify Foxp1 target genes.

overall_design: To identify potential direct target genes of Foxp1 in kidney distal tubules, we performed ChIP-seq analysis with kidney tissues from Foxp1kspKO and littermate control mice.

first: Shi-Ting

last: Wu

first: Dongbo

last: Lu

first: Yu

last: Feng

first: Renhua

last: Song


title: Identification of expression patterns of FoxP1 in the kidneys using RiboTag mice and RNA sequencing

type: Expression profiling by high throughput sequencing

summary: Intercalated cells within renal tubules play a vital role in maintaining body acid-base balance through H+ and HCO3- secretion. Disruptions in intercalated cell differentiation or channel activity due to gene mutations can lead to distal renal tubular acidosis (dRTA), yet the precise mechanisms governing this process remain poorly understood. This study identified Foxp1 and its downstream factors as novel essential factors for intercalated cell differentiation, thus shed light on potential underlying mechanisms in some unresolved cases of dRTA.

overall_design: To investigate the role of Foxp1 in kidney collecting tube, we generated the Cdh16-cre;Foxp1fl/fl (thereafter denoted as FoxP1kspKO) by crossing the Foxp1fl/fl mice with the Cdh16-Cre (also known as the Ksp-Cre) mice. In these mice, FoxP1 is conditionally knocked out in kidney tubular cells and the absence Foxp1 expression in kidney tubular cells was confirmed by immunostaining.


title: Histone ChIP-seq from BLaER1 (ENCSR011IBZ)

summary:
H3K4me1 ChIP-Seq on BLaER1 cell line after 48 h treatment with 100 nM 17β-estradiol, 10 ng/mL Interleukin-3, 10 ng/mL CSF1.

For data usage terms and conditions, please refer to http://www.genome.gov/27528022 and http://www.genome.gov/Pages/Research/ENCODE/ENCODE_Data_Use_Policy_for_External_Users_03-07-14.pdf


title: Histone ChIP-seq from BLaER1 (ENCSR192IRQ)

summary:
H3K9ac ChIP-Seq on BLaER1 cell line after 3 h treatment with 100 nM 17β-estradiol, 10 ng/mL Interleukin-3, 10 ng/mL CSF1.

For data usage terms and conditions, please refer to http://www.genome.gov/27528022 and http://www.genome.gov/Pages/Research/ENCODE/ENCODE_Data_Use_Policy_for_External_Users_03-07-14.pdf


title: Histone ChIP-seq from BLaER1 (ENCSR122IWP)

summary:
H3K4me3 ChIP-Seq on BLaER1 cell line after 48 h treatment with 100 nM 17β-estradiol, 10 ng/mL Interleukin-3, 10 ng/mL CSF1.

For data usage terms and conditions, please refer to http://www.genome.gov/27528022 and http://www.genome.gov/Pages/Research/ENCODE/ENCODE_Data_Use_Policy_for_External_Users_03-07-14.pdf


title: Cellular indexing of transcriptomes and epitopes sequencing of mobilized peripheral blood human CD34+ hematopoietic stem and progenitor cells from a healthy volunteer

status: Public on Feb 26 2024

city: Bethesda

first: Daisuke

last: Araki

state: MD

address: 9000 Rockville Pike

institute: National Institutes of Health

summary: Our research has demonstrated that high expression of surface cMPL receptor marks long-term repopulating human hematopoietic stem cells.

overall_design: G-CSF mobilized peripheral blood human CD34+ cells were obtained from a healthy volunteer and CITE-sequencing was performed.

first: Andre

last: Larochelle

first: Neelam

last: Redekar

first: Bryan

last: Fisk


title: Histone ChIP-seq from BLaER1 (ENCSR105FGG)

summary:
H3K4me3 ChIP-Seq on BLaER1 cell line after 36 h treatment with 100 nM 17β-estradiol, 10 ng/mL Interleukin-3, 10 ng/mL CSF1.

For data usage terms and conditions, please refer to http://www.genome.gov/27528022 and http://www.genome.gov/Pages/Research/ENCODE/ENCODE_Data_Use_Policy_for_External_Users_03-07-14.pdf


title: Gene-edited Mtsoc1 triple mutant Medicago plants do not flower

city: Auckland

first: Joanna

last: Putterill

state: Auckland

address: 3A Symonds Street

department: School of Biological Sciences

country: New Zealand

institute: The University of Auckland

summary:
Optimised flowering time is an important trait ensuring successful plant adaptation and crop productivity. SOC1-like genes encode
MADS transcription factors known to play important roles in flowering control in many plants. This includes the best characterised
eudicot model Arabidopsis thaliana (Arabidopsis) where SOC1 promotes flowering and functions as a floral integrator gene
integrating signals from different flowering time regulatory pathways. Medicago truncatula (Medicago) is a temperate reference
legume with strong genomic and genetic resources used to study flowering pathways in legumes. Interestingly, despite responding
to the similar floral-inductive cues of extended cold (vernalisation) followed by warm long days, as winter annual Arabidopsis,
Medicago lacks FLC and CO which are key regulators of flowering in Arabidopsis. Unlike Arabidopsis with one SOC1 gene, multiple
gene duplication events have given rise to three MtSOC1 paralogs within the Medicago genus in legumes; one Fabaceae group A
SOC1 gene, MtSOC1a, and two tandemly-repeated Fabaceae group B SOC1 genes, MtSOC1b and MtSOC1c. Previously, we showed that
MtSOC1a has unique functions in floral promotion in Medicago. The Mtsoc1a Tnt1 retroelement insertion single mutant showed
moderately delayed flowering in long and short day photoperiods, with and without prior vernalization, compared with wild type.
On the other hand, Mtsoc1b Tnt1 single mutants did not have altered flowering time or flower development, indicating that it was
redundant in an otherwise wild type background. Here, we describe the generation of Mtsoc1 triple mutant plants by CRISPR-Cas9
gene editing. Two independent Mtsoc1 homozygous triple mutants were non-flowering and bushy in floral inductive VLD.
Phenotyping and gene expression analyses by RNA-seq and RT-qPCR indicate that the Mtsoc1 triple mutants remain vegetative. Thus
overall, the Mtsoc1 triple mutants are dramatically different from the single Mtsoc1a mutant and the Arabidopsis soc1 mutant;
implicating multiple MtSOC1 genes in critical overlapping roles in the transition to flowering in Medicago.

overall_design: To investigate the role of Medicago SOC1 genes, we carried out RNA-seq on single Mtsoc1a mutant and gene-edited triple Mtsoc1-4 mutant and compared to the relative wildtype.

first: Axel

last: Poulet

first: Min

last: Zhao

first: Yongyan

last: Peng

first: FangFei

last: Tham

first: Mauren

last: Jaudal

first: Lulu

last: Zhang

first: Josien

middle: C

last: van Wolfswinkel


title: Circulating Monocytes are Predictive and Responsive in Moderate-to-Severe Plaque Psoriasis Subjects Treated with Apremilast

city: Cleveland

first: Thomas

middle: S

last: McCormick

state: OH

address: 2109 Adelbert Rd

department: Dermatology

institute: Case Western Reserve University

summary: Monocytes play a critical role in the inflammation associated with psoriasis, and their abnormalities have been reported as biomarkers of cardiovascular event risk, a psoriasis comorbidity. Monocytic cells in chronic inflammatory disorders express elevated levels of cAMP phosphodiesterase. Restoring cAMP levels using the oral cAMP phosphodiesterase-4 inhibitor, apremilast, improves clinical outcomes for a subset of psoriasis patients. We asked whether aberrant monocyte subsets or transcriptomic pathways can function as biomarkers of psoriasis endotypes that can predict enhanced clinical responses to cAMP phosphodiesterase inhibition. A 16-week open-label study of 22 patients with monocyte flow cytometric and transcriptomic analysis was performed. Subjects with elevated hyper-adhesive monocyte doublets at baseline were more likely to be responders to apremilast (p< 0.0001); 82% of subjects with elevated hyper-adhesive monocyte doublets achieved 50% reduction in PASI (PASI50) compared to 46% in those without elevated doublets. We observed a significant reduction in hyper-adhesive monocyte-containing doublets and monocyte-platelet aggregates, suggesting an effect of apremilast on the adhesiveness of blood monocytes during chronic inflammation. Monocyte differentially-expressed gene transcripts predictive of clinical response uncovered pharmaco-endotypes with distinct patterns of nucleotide metabolism, energetics, and differentiation. Further study to understand the basis of drug responsiveness, and to develop an apremilast psoriasis treatment algorithm using monocyte refined gene expression is required to validate and become practical in clinical use, offering patients a test that personalizes their likelihood of clinical response.

overall_design: To examine CD14+ monocyte gene expression in moderate-to-severe plaque psoriasis patients based on response to apremilast.

first: Emma

middle: L

last: Larson

first: Dustin

middle: P

last: DeMeo

first: Kevin

middle: D

last: Cooper


title: sc-RNA sequencing data of primary liver cells from wildtype, YAPKO,TAZKO and DKO mice

city: Heidelberg

first: Kai

last: Breuhahn

address: Im Neuenheimer Feld 224

country: Germany

institute: Heidelberg University

summary:
Background & Aims
The Hippo pathway and its transcriptional effectors yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ) are promising targets for cancer therapy. However, it is not understood if inhibition of one factor is compensated by the activation of the other and if YAP/TAZ-directed perturbation affects cell-cell communication of non-malignant liver-resident cells.
Methods
Mice with hepatocyte (HC)-/biliary epithelial cell (BEC)-specific deletions of YAP and/or TAZ were generated (YAPKO, TAZKO and double knock-out (DKO)). Liver tissues were investigated by histology, immunohistochemistry, and single cell RNA-sequencing (scRNA-seq). Serum samples were analyzed using a cytokine array.
Results
Liver tissues from YAPKO and DKO mice were characterized by the loss of BECs, liver fibrosis, and necrosis. This phenotype was weakened in DKO tissues compared to specimen from YAPKO animals. YAP expression was induced in different non-parenchymal cells (NPCs) after YAP-depletion in HCs and BECs. Activation of YAP in Kupffer cells (KCs) and endothelial cells (ECs) in subclusters with specific molecular features was independent of cholestasis. Pro-inflammatory chemokines and cytokines such as interleukin-1 (IL1) and intercellular adhesion molecule-1 (ICAM1) were detected in the serum of YAPKO animals. YAP-interacting TEA domain transcription factor (TEAD) family members bound promoter regions of different secreted factors and may contribute to a severe inflammatory response in mice with YAP-inactivation in HCs and BECs.
Conclusions
YAP inactivation causes severe liver damage in vivo and concomitant TAZ deletion does not enhance but moderately reduce this phenotype. Furthermore, we describe a new mechanism how YAP inactivation in HCs/BECs contributes to YAP-driven heterologous cell communication originating from NPCs.

overall_design: sc-RNA sequencing data were generared from primary liver cells of  wildtype (n=1), YAPKO(n=1),TAZKO(n=1) and DKO (n=1) mice

first: Kaijing

last: Liu

first: David

last: Ibberson


title: 5’ isoforms of miR-1246 have distinct targets and stronger functions compared to canonical miR-1246 in colorectal cancer cells in vitro

city: Kaunas

first: Jurgita

last: Skiecevičienė

address: Eiveniu str. 4

department: Institute for Digestive Research

country: Lithuania

institute: Lithuanian University of Health Sciences

type: Non-coding RNA profiling by high throughput sequencing

summary: Due to alternative processing pathway and post-transcriptional modifications, precursor miRNAs maturate into various sequence isoforms (isomiRs). These sequence variations may result in the changes of the miRNA seed site, target genes, involvement in signaling pathways and thus function. It is important to mention that knowledge about the targets of isomiR is still poor. To date, isomiR research has only been performed in melanoma, breast, and gastric cancer, but there are no experimental studies conducted in colorectal cancer. Here, we aimed to evaluate the putative targets and functional role in vitro of miR-1246 and its two 5’ isoforms (ISO-miR-1246_a and ISO-miR-1246_G). To our best knowledge, this is the first study showing the important role of 5’isoforms of miR-1246 in colorectal carcinogenesis, while acting on different targetomes and being involved in distinct signaling pathways.

overall_design: Commercial Caco-2 cells of CRC origin were analyzed for expression of WT-miR-1246 and its 5 isoforms using small RNA sequencing data and overabundance of the two miR-1246 isoforms was determined. This was followed by transcriptome analysis of Caco-2 cell transfected with WT-miR-1246, ISO-miR-1246_G and ISO-miR-1246_a mimics. This study includes Caco-2 cells with no transfection.

first: Simonas

last: Juzenas

first: Rokas

last: Lukosevicius

first: Greta

last: Varkalaite


title: Incidence of microvascular dysfunction is increased in hyperlipidemic mice, reducing cerebral blood flow and impairing remote memory.

city: Bad Nauheim

first: Carsten

last: Kuenne

address: Ludwigstrasse 43

department: Bioinformatics

institute: Max Planck Institute for Heart and Lung Research

summary: The development of cognitive dysfunction is not necessarily associated with diet-induced obesity. We hypothesized that cognitive dysfunction might require additional vascular damage, for example, in atherosclerotic mice. We induced atherosclerosis in male C57BL/6N mice by injecting AAV-PCSK9DY (2x1011 VG) and feeding them a cholesterol-rich Western diet. After 3 months, mice were examined for cognition using Barnes maze procedure and for cerebral blood flow. Cerebral vascular morphology was examined by immunehistology. In AAV-PCSK9DY-treated mice, plaque burden, plasma cholesterol, and triglycerides are elevated. RNAseq analyses followed by KEGG annotation show increased expression of genes linked to inflammatory processes in the aortas of these mice. In AAV-PCSK9DY-treated mice learning was delayed and long-term memory impaired. Blood flow was reduced in the cingulate cortex (-17%), caudate putamen (-15%), and hippocampus (-10%). Immunohistological studies also show an increased incidence of string vessels and pericytes (CD31/Col IV staining) in the hippocampus accompanied by patchy blood-brain barrier leaks (IgG staining) and increased macrophage infiltrations (CD68 staining). We conclude that the hyperlipidemic PCSK9DY mouse model can serve as an appropriate approach to induce microvascular dysfunction that leads to reduced blood flow in the hippocampus, which could explain the cognitive dysfunction in these mice.

overall_design: RNA sequencing (RNAseq) analysis was performed in the descending aorta. Aortic tissue was isolated, trimmed from fat, and snap frozen in liquid nitrogen. Total RNA was isolated with the RNA Mini Kit from Bio& SELL (Nuremberg, Germany) combined with on-column DNase digestion (DNase-Free DNase Set, Qiagen) to avoid genomic DNA contamination. RNA and library preparation integrity were verified with LabChip Gx Touch 24 (Perkin Elmer). As input for VAHTS Stranded mRNA-seq Library preparation, 500 µg of total RNA was used following the manufacturer’s protocol (Vazyme). Sequencing was performed on a NextSeq2000 instrument (Illumina) with 1x72-bp single-end setup. The resulting raw reads were assessed for quality, adapter content, and duplication rates with FastQC (RRID:SCR_014583) (Andrews Simon: Andrews Simon: FastQC: a quality control tool for high-throughput sequence data. Available online at http://www.bioinformatics.babraham.ac.uk/projects/fastqc). Trimmomatic version 0.39 was employed to trim reads after a quality drop below a mean of Q15 in a window of 5 nucleotides and keeping only filtered reads longer than 15 nucleotides (20). Reads were aligned versus Ensembl mouse genome version mm10 (Ensembl release 101) with STAR 2.7.10a (21). Aligned reads were filtered to remove duplicates with Picard 2.27.4 (Picard: A set of tools in Java for working with next-generation sequencing data in the BAM format), multi-mapping, ribosomal, or mitochondrial reads. Gene counts were established with featureCounts 2.0.4 by aggregating reads overlapping exons on the correct strand, excluding those overlapping multiple genes (22). The raw count matrix was normalized with DESeq2 version 1.36.0 (23). Contrasts were created with DESeq2 based on the raw count matrix. Genes were classified as significantly differentially expressed at average count > 5, multiple testing adjusted p-value < 0.05, and -0.585 < log2FC > 0.585. The Ensemble annotation was enriched with UniProt data (Activities at the Universal Protein Resource (UniProt))

first: Luis

last: Hernandez Torres

first: Flavia

last: Rezende

first: Eva

last: Peschke

first: Olga

last: Will

first: Jan-Bernd

last: Hoevener

first: Frauke

last: Spiecker

first: Ümit

last: Özorhan

first: Josephine

last: Lampe

first: Ines

last: Stölting

first: Zouhair

last: Aherrahrou

first: Kristina

last: Kusche-Vihrog

first: Urte

last: Matschl

first: Susanne

last: Hille

first: Ralf

last: Brandes

first: Markus

last: Schwaninger

first: Oliver

middle: J

last: Müller

first: Walter

last: Raasch


title: Ribosome profiling experiment characterising early response of Lactococcus Lactis infected in sk1 bacteriophage

city: Cork

first: Martina

last: Yordonova

address: Western road

department: School of Biochemistry and Cell Biology

country: Ireland

institute: University College Cork

summary: Time-series ribosome profiling experiment. It consists of mock and sk1 bacteriophage infected samples of Lactococcus Lactis at three different timepoints; 2,5 and 15 minutes post infection

overall_design: Time-series ribosome profiling experiment. infection

first: Patrick

middle: B

last: O’Connor

first: Jennifer

last: Mahony

first: Eoghan

last: Casey

first: Pavel

middle: V

last: Baranov

first: Douwe

last: van Sinderen

middle: M

last: Yordanova


title: Effect of VEGF-C treatment on sorted brain microglia/macrophages

city: New Haven

first: Jean-Leon

last: Thomas

state: CT

address: 800 Howard Ave

institute: Yale University

summary: Meningeal lymphatic vessels (MLVs) promote tissue clearance and immune surveillance in the central nervous system (CNS). Vascular endothelial growth factor-C (VEGF-C) regulates MLV development and maintenance and has therapeutic potential for treating neurological disorders. Herein, we investigated the effects of VEGF-C overexpression on brain fluid drainage and ischemic stroke outcomes in mice. Intra-cerebrospinal administration of an adeno-associated virus expressing mouse full-length VEGF-C (AAV-mVEGF-C) increased CSF drainage to the deep cervical lymph nodes (dCLNs) by enhancing lymphatic growth, and upregulated neuroprotective signaling pathways identified by single nuclei RNA sequencing of brain cells. In a mouse model of ischemic stroke, AAV-mVEGF-C pretreatment reduced stroke injury and ameliorated motor performances in the subacute stage, associated with mitigated microglia-mediated inflammation and increased BDNF signaling in brain cells. Neuroprotective effects of VEGF-C were lost upon ligation of the dCLN afferent lymphatics, and not mimicked by acute post-stroke VEGF-C injection. We conclude that VEGF-C prophylaxis promotes multiple vascular, immune, and neural responses that culminate in a protection against neurological damage in acute ischemic stroke.

overall_design: For evaluating the effect of VEGFc-mediated meningeal lymphatic expansion on brain myeloid cells, we treated C57/Bl6J mice with AAV-CTRL or AAV-VEGFc for 4 weeks. Half of the samples were obtained at this time point. For the other half of samples, tMCAO was performed and the infarcted hemisphere was isolated 7 days after. Samples were processed with MACS bead-based myelin removal followed by purification of CD11b+ microglia/macrophages using MACS beads. Isolated cells were then lysed for mRNA isolation and sequencing. We then performed gene expression analysis with RNAseq data.

first: Ligia

last: Braga Boisserand

first: Luiz

middle: H

last: Medeiros Geraldo

first: Mark

last: Robinson


title: Histone ChIP-seq from BLaER1 (ENCSR285PDU)

first: ENCODE

last: DCC

summary:
H3K27me3 ChIP-Seq on BLaER1 cell line after 24 h treatment with 100 nM 17β-estradiol, 10 ng/mL Interleukin-3, 10 ng/mL CSF1.

For data usage terms and conditions, please refer to http://www.genome.gov/27528022 and http://www.genome.gov/Pages/Research/ENCODE/ENCODE_Data_Use_Policy_for_External_Users_03-07-14.pdf


title: The AsiDNA™ decoy mimicking DSBs protects the normal tissue from radiation toxicity through a DNA-PK/p53/p21-dependent G1/S arrest.

city: Orsay

first: Anouk

last: Sesink

address: Rue Henri Becquerel

country: France

institute: Institut Curie

summary: AsiDNA, a cholesterol-coupled oligonucleotide mimicking double-stranded DNA breaks, was developed to sensitize tumour cells to radio- and chemotherapy. This drug acts as a decoy hijacking the DNA damage response. Previous studies have demonstrated that standalone AsiDNA administration is well tolerated with no additional adverse effects when combined with chemo- and/or radiotherapy. This lack of normal tissue complication encouraged further examination into the role of AsiDNA in normal cells. The delayed development of pulmonary fibrosis after FLASH-RT compared to CONV-RT might be a known phenomenon but the complexity behind this specific tissue response is completely unidentified. Radiation has been shown to impact various cell types presented in the lung, resulting in changes in cellular activity and numerous pathway activations. Current unpublished data suggest a clear variety between the CONV and FLASH-RT gene signatures examined using single cell RNA sequencing. As the combined treatment of AsiDNA with CONV-RT resulted in a delay in radiation induced lung fibrosis compared to CONV-RT standalone, it is to be questioned if the signature of AsiDNA CONV-RT is similar to FLASH-RT or CONV-RT. To characterize the similarity in cellular changes and expression signatures in lungs 5 months post CONV-RT, FLASH-RT, AsiDNA CONV-RT or non-irradiated (Control) treatment. Single cell RNA sequencing of irradiated lungs revealed a closer resemblance between CONV AsiDNA and FLASH-RT in profibrotic gene signatures within the fibroblast and macrophages population, in comparison to CONV-RT standalone. Collectively, this information indicates that the activity of AsiDNA and FLASH-RT could draw upon identical mechanism interference to result in the protective capacities within the normal tissue.

overall_design: Single-cell suspensions were prepared from 5 month C57BL/6J mice and single cell RNA-seq libraries were generated using 3' V3 or 3'V3 NextGem chemistry kit on Chromium Single cell controller (10x Genomics). This dataset includes 3 samples: 1 sample 5 months 13 Gy post-CONV irradiation; 1 sample 5 months 13 Gy post-CONV irradiation with AsiDNA drug treatment; 1 sample 5 months 13 Gy post-FLASH irradiation.

first: A

first: M

last: Dubail

first: J

last: Soulier

first: C

last: Fouillade

first: P

last: Girard


title: RNA-seq for blood Ly6Chi and Ly6Clo monocyte in WT and RBP-Jfl/fl Lyz2-Cre mice

city: Beijing

first: Tiantian

last: Kou

address: Haidian  District

country: China

institute: Tsinghua university

summary: To evaluate the consequences of RBP-J loss of function in blood monocyte subsets, we sequenced RNA of blood Ly6Chi monocyte and Ly6Clo monocyte from  WT and RBP-Jfl/fl Lyz2-Cre mice.

overall_design: Blood Ly6Chi and Ly6Clo monocytes were isolated from WT and RBP-Jfl/fl Lyz2-Cre mice, and total RNA was extracted using total RNA purification kit. RNA was converted into RNA-seq quantification libraries, and RNA-seq libraries were sequenced with the pair-end option.

first: Lan

last: Kang

first: Bin

last: Zhang


title: DNA Methylation Potential Energy Landscape Analysis of Diffuse Midline Glioma/Diffuse intrinsic pontine glioma (DMG/DIPG RNA-Seq)

status: Public on Feb 25 2024

city: Baltimore

first: Michael

middle: A

last: Koldobskiy

address: 855 N. Wolfe St.

department: Center for Epigenetics

institute: Johns Hopkins University

summary: Diffuse intrinsic pontine glioma (DIPG) is a uniformly lethal brainstem tumor of childhood, driven by mutations in histone H3 at lysine 27 (K27M) leading to altered epigenetic regulation. Epigenomic analyses of DIPG have shown global loss of repressive chromatin marks accompanied by DNA hypomethylation. However, studies providing a static view of the epigenome do not adequately capture the regulatory underpinnings of DIPG intratumoral heterogeneity and phenotypic plasticity. To address this, we performed whole-genome bisulfite sequencing (WGBS) on 23 primary patient DIPG specimens, 4 patient-derived DIPG neurosphere cell lines, and 5 normal controls and applied a novel framework for analysis of DNA methylation variability, permitting the derivation of comprehensive genome-wide DNA methylation potential energy landscapes that capture intrinsic epigenetic variation. We show that DIPG exhibits a markedly disordered epigenome, with increasingly stochastic DNA methylation localizing to key regulatory elements and genes. We demonstrate marked epigenetic instability at genes regulating pluripotency and developmental identity, potentially enabling cells to sample a diverse range of transcriptional programs and differentiation states. We then evaluated the responsiveness of the DIPG epigenetic landscape to pharmacologic modulation. Treatment with the DNA hypomethylating agent decitabine produced profound genome-wide demethylation and reduced DNA methylation stochasticity at active enhancers, bivalent promoters, and promoters of key developmental genes. Decitabine treatment elicited changes in gene expression, including upregulation of immune signaling, and sensitized DIPG cells to the effects of histone deacetylase inhibition. This study provides a resource for dissecting the epigenetic instability that underlies DIPG heterogeneity and plasticity, suggesting the application of epigenetic therapies to constrain the range of epigenetic states available to DIPG cells.

overall_design: RNA-seq of indicated patient-derived DIPG neurosphere cell lines after treatment with DMSO control of decitabine (DAC), in triplicate.

first: Ashley

middle: R

last: Tetens


title: Histone ChIP-seq from BLaER1 (ENCSR048RSQ)

summary:
H3K4me2 ChIP-Seq on BLaER1 cell line after 18 h treatment with 100 nM 17β-estradiol, 10 ng/mL Interleukin-3, 10 ng/mL CSF1.

For data usage terms and conditions, please refer to http://www.genome.gov/27528022 and http://www.genome.gov/Pages/Research/ENCODE/ENCODE_Data_Use_Policy_for_External_Users_03-07-14.pdf


title: Seven chain adaptive immune receptor repertoire analysis in rheumatoid arthritis reveals novel features associated with disease and clinically relevant phenotypes

status: Public on Feb 23 2024

city: Barcelona

first: Antonio

last: Julià

state: Barcelona

address: c/ Baldiri Reixac nº15

department: Rheumatology Research Group

country: Spain

institute: Vall d'Hebron Hospital Research Institute

summary: In rheumatoid arthritis (RA), the activation of T and B cell clones specific for self-antigens leads to the chronic inflammation of the synovium. Here, we perform an in-depth quantitative analysis of the seven chains that comprise the adaptive immune receptor repertoire (AIRR) in RA. In comparison to controls, we show that RA patients have multiple and strong differences in the BCR repertoire including reduced diversity as well as altered isotype, chain and segment frequencies. We demonstrate that therapeutic TNF inhibition partially restores this alteration but find a profound difference in the underlying biochemical reactivities between responders and non-responders. Combining the AIRR with HLA typing, we identify the specific TCR repertoire associated with disease risk variants. Integrating these features, we further develop a molecular classifier that shows the utility of the AIRR as a diagnostic tool. Simultaneous sequencing of the seven chains of the human AIRR reveals novel features associated with the disease and clinically relevant phenotypes, including response to therapy. These findings show the unique potential of AIRR to address precision medicine in immune-related diseases.

overall_design:
Three complementary study designs were conducted to characterize the immune repertoire of RA, including case-control, case-case and longitudinal analyses
Please note that the gender information for each sample (included in mixed sample records) is provided in the corresponiding sample description field.

first: Adrià

last: Aterido


title: Super enhancer dysregulation in rhabdoid tumor cells is regulated by the SWI/SNF ATPase BRG1

city: Nashville

first: Jing

last: Wang

state: TN

address: 2220 Pierce Avenue

institute: Vanderbilt University Medical Center

summary: Mutations in the SWI/SNF chromatin remodeling complex occur in ~20% of cancers. In rhabdoid tumors defined by loss of the SWI/SNF subunit SMARCB1, dysregulation of enhancer-mediated gene expression is pivotal in driving oncogenesis. Enhancer dysregulation in this setting is tied to retention of the SWI/SNF ATPase BRG1—which becomes essential in the absence of SMARCB1—but precisely how BRG1 contributes to this process remains unknown. To characterize how BRG1 participates in chromatin remodeling and gene expression in SMARCB1-deficient cells, we performed a genome-wide characterization of the impact of BRG1 depletion in multiple rhabdoid tumor cell lines. We find that although BRG1-regulated open chromatin sites are distinct at the locus level, the biological characteristics of the loci are very similar, converging on a set of thematically related genes and pointing to involvement of the AP-1 transcription factor. The open chromatin sites regulated by BRG1 colocalize with histone-marked enhancers and intriguingly include almost all super-enhancers, revealing that BRG1 plays a critical role in maintaining super-enhancer function in this setting. These studies can explain the essentiality of BRG1 to rhabdoid tumor cell identity and survival and implicate the involvement of AP-1 as critical downstream effector of pro-tumorigenic transcriptional programs.

overall_design: We used rhabdoid tumor cell lines derived from various tissues and interrogated the contribution of BRG1 to gene regulation using the well-characterized BRG1 chemical degrader called ACBI1. We performed chromatin binding assays, transcriptomic assays, and chromatin accessibility assays.

first: April

last: Weissmiller

first: William

last: Tansey

first: Qi

last: Liu


title: Nuclear microRNA-mediated transcriptional control determines adult microglial homeostasis and brain function [cKO+Pu.1 inhibitor RNA-seq]

status: Public on Feb 22 2024

city: Kunming

first: ying

last: cheng

state: Yunnan

address: University East Outer Ring South Road

department: lnstitute of Biomedical Research

institute: YunnanUniversity

summary: Microglia are versatile regulators in brain development and disorders. Emerging evidence links miRNA-mediated regulation to microglial function; however, the exact underlying mechanism remains largely unknown. Here, we discover that miR-137, a neuropsychiatric disorders-associated miRNA, is abundant in the microglial nucleus and exhibits unexpected epigenetic functions in maintaining the global transcriptomic state, core properties, and functions of microglia. Mechanistically, microglial Mir137 deletion increases the accessibility of chromatin, which harbors binding motifs of microglial master transcription factor Pu.1. Our biochemical and bioinformatics analyses suggest that miR-137 can interact with Pu.1, thus influencing Pu.1-mediated gene expression. Importantly, we find that increased Pu.1 binding upregulates the target gene Jdp2, and Jdp2 knockdown markedly suppresses the impaired cellular phenotypes in Mir137 knockout microglia. Collectively, our study provides evidence supporting a notion that miR-137 acts as an epigenetic regulator, and this microglia-specific function is essential to maintain normal adult brain function.

overall_design: We generated microglia-specific Mir137 knockout mice to investigate the role of miR-137 in microglia in adult mice. To do so, we crossed Mir137loxP/loxP mice with transgenic mice bearing a tamoxifen-inducible Tmem119-CreERT2 allele. After 7 consecutive days injection of tamoxifen at 7–8 weeks of age, we obtained the mice with correct genotypes, including Mir137+/+;Tmem119-CreERT2 (cWT) and Mir137loxP/loxP;Tmem119-CreERT2 (cKO). The primary microglia of adult mice (n = 4) were gently isolated and purified. To investigate the transcriptional changes up the loss of miR-137, we performed RNA-seq for Mir137 cWT and cKO microglia. Three replicates were included for each genotype.

first: Kexin

last: Mao


title: Gene regulatory basis of bystander activation in CD8+ T cells

city: Ithaca

first: Andrew

last: Grimson

state: NY

address: 445 Biotech Bldg

department: Molecular Biology and Genetics

institute: Cornell University

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

sample_organism:
Homo sapiens
Mus musculus

platform_organism:
Homo sapiens
Mus musculus

overall_design: Refer to individual Series


title: Regulatory small RNA profiling of  first-trimester maternal plasma-derived exosome content in preeclampsia aggravated with intrauterine growth restriction

city: Budapest

first: Tamás

middle: István

last: Orbán

address: Magyar tudósok körútja 2.

department: Enzimology Institute

country: Hungary

institute: Research Centre for Natural Sciences

summary: Preeclampsia (PE) is a pregnancy related multisystemic syndrome, which shows symptomes after the 20th week of the pregnancy. It affects 5-8% of all pregnancies, caused by placental disfunction and commonly combined with fetal intrauterine growth restriction (IUGR). Exosomes mediate cell-to-cell communication with their cargo, such as different types of RNA molecules. The exosomal RNA cargo is unique, gives information about the molecular condition of the donor cells and promotes altered gene expression in the acceptor cells. To address a better understanding of the pathophysiological mechanism of PE combined with IUGR, we investigated the differences of plasma exosomal regulatory small RNA content between healthy and PE+IUGR pregnancies before the development of symptoms. We created a high-throughput exosomal small RNA sequencing based method using first-trimester maternal plasma samples from 5 control and  5 PE+IUGR pregnancies to find differences in regulatory small RNA expression levels, such as miRNAs and piRNAs. The differential exosomal expression was corrected for the completed gestational weeks at sampling time calculated on the basis of the Crown-Rump Length (CRL). The analysis has shown differential exosomal expression in case of 16 miRNAs and 6 piRNAs in the PE+IUGR pregnancies compared to normal conditions (p-value ≤ 0.05) . All of the miRNAs and 3 piRNAs were up-regulated, wherease 3 piRNAs were down-regulated. Our results also supported the importance of gestational age at sampling time on exosomal small RNA expression.

overall_design: Exosomal small RNA profile of first-trimester derived plasma samples in case of 5 control and 5 preeclampsia plus intrauterine growth restriction (PE+IUGR) pregnancies.

first: Luca

last: Gál

first: Ábel

last: Fóthi

first: Gábor

middle: N

last: Than


title: Blood–brain barrier disruption and sustained systemic inflammation in individuals with long COVID-associated cognitive impairment

city: Dublin

first: Chris

last: Greene

address: 123 St Stephen's Green

department: Physiology & Medical Physics

institute: Royal College of Surgeons in Ireland

summary: Vascular disruption has been implicated in COVID-19 pathogenesis, and may predispose to the neurological sequelae associated with the condition (known as Long COVID), yet it remains unclear how blood-brain barrier (BBB) function is affected in these conditions. Here, we show that BBB disruption is evident during acute infection and in Long COVID patients with cognitive impairment, commonly referred to as brain fog. Using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), we show BBB disruption correlated with brain volume changes. Transcriptomic analysis of peripheral blood mononuclear cells (PBMCs) revealed dysregulation of the coagulation system and a dampened adaptive immune response in individuals with brain fog. Accordingly, PBMCs showed increased adhesion to human brain endothelial cells in vitro, while exposure of endothelial cells to serum from Long COVID patients induced expression of inflammatory markers. Together, our data suggest that sustained systemic inflammation and persistent localised BBB dysfunction is a key feature of Long COVID-associated brain fog.

overall_design: To investigate the role of systemic inflammation in Long COVID we performed RNA seq on peripheral blood mononuclear cells from unaffected controls, patients recovered from SARS-CoV-2 infection and Long COVID patients with or without cognitive impairment, also known as brain fog.

first: Matthew

last: Campbell


title: Locus-specific LINE-1 expression in clinical ovarian cancer specimens at the single-cell level

city: Helsinki

first: Anna

last: Perkiö

address: Haartmaninkatu 8

country: Finland

institute: University of Helsinki

summary: Long interspersed nuclear elements (LINE-1s or L1s) are a group of retrotransposons that can copy themselves within a genome. In our species, it is the most successful transposon in nucleotide content. L1 expression is generally mild in normal human tissues, but the activity has been shown to increase significantly in many cancers. Only few studies have examined L1 expression at single-cell resolution, thus it is undetermined whether L1 reactivation occurs solely in malignant cells within tumors. One of the cancer types with frequent L1 activity is high-grade serous ovarian carcinoma (HGSOC). Here, we identified locus-specific L1 expression with 3’ single-cell RNA sequencing in pre- and post-chemotherapy HGSOC sample pairs from 11 patients, and in fallopian tube samples from five healthy women. Although L1 expression quantification with the chosen technique was challenging due to the repetitive nature of L1 elements, we found evidence of genuine L1 expression. The expression levels were similar in pre- and post-chemotherapy samples, indicating that L1 transcriptional activity was unaffected by the treatment. Furthermore, we found that L1 activity was negatively associated with the expression of MYC target genes, a finding that supports earlier literature of MYC being an L1 suppressor.

overall_design:
We studied LINE-1 expression in 22 high-grade serous ovarian cancer patient samples collected concurrently with both laparoscopy and interval debulking surgery from 11 women, as well as in five non-cancerous fallopian tube or fimbria tissue samples from five healthy post-menopausal women. We used scRNA-seq to get a single-cell level view of the expression profiles.
----------------------------
Authors state:
Raw data files are not included. The raw data has been uploaded to EGA (EGAS00001006246 for fallopian tube/fibmriae samples,  EGAS00001005010 for cancer samples) in order to comply with data protection regulations.

first: Barun

last: Pradhan

first: Sanna

last: Pikkusaari

first: Kaisa

last: Huhtinen

first: Kaiyang

last: Zhang

first: Sara

last: Narva

first: Johanna

last: Hynninen

first: Liisa

last: Kauppi

first: Erdogan

last: Erkan

last: Vähärautio


title: Transcriptome-wide profiling of different mouse adipose tissues during aging using snRNA-seq

first: Meng

last: Xie

state: Beijing

address: No.5 Yiheyuan Road, Haidian District

institute: Peking University

summary: We found the mPRAT adipose undergoes a whitning process which differs from iBAT and iWAT. The whitened adipocytes can still respond to cold exposure, which has cellular and molecular differences compared with iBAT and iWAT.

overall_design: Different mouse adipose depots including brown and white adipose tissue were collected at different ages for comparison. Besides, the depot-specific cold-response was compared.

first: Houyu

first: Yan

last: Li

first: Carlos

middle: F

last: Ibáñez


title: Chronic stress causes metastasis via neutrophil-mediated changes to the microenvironment.

city: CLEVELAND

first: Yuan

last: Gao

address: 2109 Adelbert Rd., Wood Building Research Tower 300-7, Wood Building Research Tower 300-7

department: Pharmacology

institute: Case Western Reserve University

summary: We report the mechanism linking chronic stress with increased cancer metastasis risk.

overall_design: RNA-seq  experiments in murine lung tissue or breast cancer tumors under chronic stress, and RNA-seq and ChIP-seq experiments in murine bone marrow isolated neutrophils treated with different glucocorticoid receptor agonists.

first: Xue-Yan

last: He

first: Mikala

last: Egeblad


title: Nuclear microRNA-mediated transcriptional control determines adult microglial homeostasis and brain function [cKO scRNA-Seq]

first: ying

last: cheng

overall_design: We generated microglia-specific Mir137 knockout mice to investigate the role of miR-137 in microglia in adult mice. To do so, we crossed Mir137loxP/loxP mice with transgenic mice bearing a tamoxifen-inducible Tmem119-CreERT2 allele. After 7 consecutive days injection of tamoxifen at 7–8 weeks of age, we obtained the mice with correct genotypes, including Mir137+/+;Tmem119-CreERT2 (cWT) and Mir137loxP/loxP;Tmem119-CreERT2 (cKO). The primary microglia of adult mice (n = 4) were gently isolated and purified. To investigate the transcriptional changes up the loss of miR-137, we performed RNA-seq for Mir137 cWT and cKO microglia. Two replicates were included for each genotype in single cell RNA-seq.

first: Kexin

last: Mao


title: Nuclear microRNA-mediated transcriptional control determines adult microglial homeostasis and brain function [gKO RNA-seq]

overall_design: We generated Mir137 knockout mice to investigate the role of miR-137 in mice. To do so, we obtained the mice with correct genotypes, including Mir137 gWT and Mir137 gKO. The primary microglia of adult mice (n = 4) were gently isolated and purified. To investigate the transcriptional changes up the loss of miR-137, we performed RNA-seq for Mir137 gWT and gKO microglia. Three replicates were included for each genotype.


title: Nuclear microRNA-mediated transcriptional control determines adult microglial homeostasis and brain function [cKO RNA-seq]


title: Nfe2l3 promotes neuroprotection and long-distance axon regeneration after injury in vivo [bulkRNA-seq]

city: Farmington

first: Ephraim

last: Trakhtenberg

address: 263 Farmington Ave. RM L4005

department: Neuroscience

institute: University of Connecticut School of Medicine

summary: Nuclear factor erythroid 2 like (Nfe2l) gene family members 1-3 mediate cellular response to oxidative stress, including in the central nervous system (CNS). However, neuronal functions of Nfe2l3 are unknown. Here, we comparatively evaluated expression of Nfe2l1, Nfe2l2, and Nfe2l3 in singe cell RNA-seq (scRNA-seq)-profiled cortical and retinal ganglion cell (RGC) CNS projection neurons, investigated whether Nfe2l3 regulates neuroprotection and axon regeneration after CNS injury in vivo, and characterized a gene network associated with Nfe2l3 in neurons. We showed that, Nfe2l3 expression transiently peaks in developing immature cortical and RGC projection neurons, but is nearly abolished in adult neurons and is not upregulated after injury. Furthermore, within the retina, Nfe2l3 is enriched in RGCs, whereas Nfe2l1 and Nfe2l2 are expressed robustly in other retinal cell types as well, and are also upregulated after injury. We also found that, expressing Nfe2l3 in injured RGCs through localized intralocular viral vector delivery promotes neuroprotection and long-distance axon regeneration after optic nerve injury in vivo. Moreover, Nfe2l3 treatment provided a similar extent of neuroprotection and axon regeneration as viral vector-targeting of Pten and Klf9, which are prominent regulators of neuroprotection and long-distance axon regeneration. Finally, we bioinformatically characterized a gene network associated with Nfe2l3 in neurons, which revealed the association of Nfe2l3 with established mechanisms of neuroprotection and axon regeneration. Thus, Nfe2l3 is a novel neuroprotection and axon regeneration-promoting factor with a therapeutic potential for treating CNS injury and disease.

overall_design: Bulk-RNA-seq samples from postnatal day 5 RGCs were purified by immunopanning for Thy1 (after immunopanning depletion of macrophages). RNA with RNA Integrity Number (RIN) ≥ 9 (by Bioanalyzer 2100 using the Nano 6000 kit, Agilent) was extracted using Direct-zol RNA MiniPrep kit (R2050, Zymo Research). The RNA was processed and cDNA libraries were prepared using RiboZero and ScriptSeq v2 kit (Epicentre) which depletes rRNAs. Paired reads were sequenced in a DNA-strand-specific manner, 100 bp from each end, on HiSeq 2000 Sequencer (Illumina), passed QC filters, mapped to the mm10 genome and transcriptome by Hisat2, and analyzed by Cufflinks/CuffDiff. Transcript isoforms expressed > 0.1 FPKM were retained and visualized using IGV browser.

first: Agnieszka

last: Lukomska

first: Matthew

last: Frost


title: 5’ isoforms of miR-1246 have distinct targets and stronger functions compared to canonical miR-1246 in colorectal cancer cells in vitro

first: Jurgita

last: Skiecevičienė

address: Eiveniu str. 4

institute: Lithuanian University of Health Sciences

summary: Due to alternative processing pathway and post-transcriptional modifications, precursor miRNAs maturate into various sequence isoforms (isomiRs). These sequence variations may result in the changes of the miRNA seed site, target genes, involvement in signaling pathways and thus function. It is important to mention that knowledge about the targets of isomiR is still poor. To date, isomiR research has only been performed in melanoma, breast, and gastric cancer, but there are no experimental studies conducted in colorectal cancer. Here, we aimed to evaluate the putative targets and functional role in vitro of miR-1246 and its two 5’ isoforms (ISO-miR-1246_a and ISO-miR-1246_G). To our best knowledge, this is the first study showing the important role of 5’isoforms of miR-1246 in colorectal carcinogenesis, while acting on different targetomes and being involved in distinct signaling pathways.

overall_design: Colorectal cancer (CRC) is a multifactorial disease involving genetic and epigenetic factors, such as miRNAs. Sequencing-based studies revealed that miRNAs have many isoforms (isomiRs) with modifications at 3’, 5’ ends or in the middle, resulting in distinct targetomes, and consequentially, function. In the present study, we aimed to evaluate the putative targets and functional role in vitro of miR-1246 and its two 5’ isoforms (ISO-miR-1246_a and ISO-miR-1246_G).   Commercial Caco-2, SW480 and HT-29 cells of CRC origin were analyzed for expression of WT-miR-1246 and its 5’ isoforms using small RNA sequencing data and overabundance of the two miR-1246 isoforms was determined in all cell lines. Transcriptome analysis of Caco-2 cell transfected with WT-miR-1246, ISO-miR-1246_G and ISO-miR-1246_a indicated a minor overlap of targetomes between the studied miRNA isoforms. Consequentially, enrichment analysis showed involvement of the potential targets of miR-1246 isoforms in distinct signaling pathways. Cancer related pathways were predominantly more enriched in dysregulated genes in ISO-miR-1246_G and ISO-miR-1246_a, whereas cell cycle pathways - in WT-miR-1246. Functional analysis of WT-miR-1246 and its two 5’ isoforms revealed that inhibition of any of these molecules had a tumor-suppressive role (reduced cell viability, migration, and promoted early cell apoptosis) in CRC cells. However, 5’-isoforms had a stronger effect on viability compared to WT-miR-1246.   To conclude, this research shows that WT-miR-1246 and its two 5’-isoforms have different targetomes and are involved in distinct signaling pathways, but collectively play an important role in CRC pathogenesis.

first: Rokas

last: Lukosevicius

first: Gediminas

last: Alzbutas

first: Greta

last: Varkalaite

first: Violeta

last: Salteniene

first: Deimante

last: Tilinde

first: Simonas

last: Juzenas

first: Ugne

last: Kulokiene

first: Kestutis

last: Adamonis

last: Kiudelis

first: Juozas

last: Kupcinskas

last: Skieceviciene


title: Nuclear microRNA-mediated transcriptional control determines adult microglial homeostasis and brain function [ATAC-seq]

last: cheng

overall_design: We generated microglia-specific Mir137 knockout mice to investigate the role of miR-137 in microglia in adult mice. To do so, we crossed Mir137loxP/loxP mice with transgenic mice bearing a tamoxifen-inducible Tmem119-CreERT2 allele . After 7 consecutive days injection of tamoxifen at 7–8 weeks of age, we obtained the mice with correct genotypes, including Mir137+/+;Tmem119-CreERT2 (cWT) and Mir137loxP/loxP;Tmem119-CreERT2 (cKO). The primary microglia of adult mice (n = 4) were gently isolated and purified. To investigate the most active transcription factors upon the loss of miR-137, we performed transposase-accessible chromatin sequencing (ATAC-seq) for Mir137 cWT and cKO microglia. Three replicates were included for each genotype.


title: Nuclear microRNA-mediated transcriptional control determines adult microglial homeostasis and brain function. [SuperSeries]


title: Nuclear microRNA-mediated transcriptional control determines adult microglial homeostasis and brain function [ChIP-seq]

overall_design: We generated microglia-specific Mir137 knockout mice to investigate the role of miR-137 in microglia in adult mice. To do so, we crossed Mir137loxP/loxP mice with transgenic mice bearing a tamoxifen-inducible Tmem119-CreERT2 allele. After 7 consecutive days injection of tamoxifen at 7–8 weeks of age, we obtained the mice with correct genotypes, including Mir137+/+;Tmem119-CreERT2 (cWT) and Mir137loxP/loxP;Tmem119-CreERT2 (cKO). The primary microglia of adult mice (n = 4) were gently isolated and purified. To investigate the transcriptional regulation of miR-137, we performed chromatin immunoprecipitation sequencing (ChIP-seq) of Pu.1, H3K4me3, H3K27ac, Pol II, and Pol II Ser5P for Mir137 cWT and cKO microglia. Three replicates were included for each genotype.

last: Mao


title: Hypoxia-induced expression of Tfcp2l1 promotes cell immortalization by enhancing cellular reprogramming

city: Seville

first: José

middle: M.

last: Santos-Pereira

address: Avda. Manuel Siurot s/n

institute: IBiS, Universidad de Sevilla-CSIC

summary: Cellular senescence is a stress response mechanism maintaining tissue homeostasis by changing physiological state and inducing irreversible proliferative arrest. It has been reported that hypoxia can bypass senescence and extend lifespan of naïve primary cells, mainly, by the decrease in oxidative damage. However, it is unclear how hypoxia can promote the evasion of senescence and promote cell immortalization prior to malignant transformation.  We observed that the lifespan of MEFs is increased when they are cultured in hypoxia, reducing the expression of p16INK4a, p15INK4b and p21Cip1. In transcriptional genetic screenings, we found that proliferating naïve MEFs in hypoxia overexpress Tfcp2l1, which is a main regulator of pluripotency and self-renewal in embryonic stem cells, ESCs, as well as stemness-associated genes like Oct3/4, Sox2, Nanog. Tfcp2l1 expression is lost during culture in normoxia. The expression of Tfcp2l1 in hypoxia seems to be regulated by Hif1α and only when it is overexpressed at similar levels to those induced physiologically by hypoxia it increases lifespan of MEFs and promotes overexpression of stemness-associated genes. In Chip-seq experiments, we found that Tfcp2l1 binds and activate the expression of genes which regulate proliferation, which in many cases, are also related to stem cell properties, such as Sox2, Sox9 and Tgfa. Additionally, Tfcp2l1 can replicate the effect of hypoxia increasing cellular reprogramming and its expression correlates positively with the expression of Nanog and negatively with p21Cip1 and p16INK4a.  Altogether, our data suggests that the activation of Tfcp2l1 by hypoxia could be relevant in the immortalization prior to malignant transformation, facilitating tumorigenesis and dedifferentiation of cells.

overall_design: ChIP-seq and ATAC-seq assays in MEFs undergoing senescence in normoxia or immortalized in hypoxia

first: Daniel

last: Otero-Albiol

first: Antonio

last: Lucena-Cacace

first: Yoshinori

last: Yoshida

first: Amancio

last: Carnero


title: Mouse Striatum scRNAseq:2months of age

status: Public on Feb 21 2024

city: Los Angeles

first: Kay

last: Linker

state: California

address: 10833 Le Conte Avenue, 53-263 CHS

department: Physiology

institute: UCLA

summary: The striatum is a functionally diverse brain region. We investigated astrocyte and glia diversity within this brain region.

overall_design: To investigate the functional heterogeneity of astrocytes from a defined brain region, we performed single cell RNA-seq of striatal cells from adult mice (8-9 weeks old).

first: Baljit

last: Khakh


title: Maternal RNA transcription in Dlk1-Dio3 domain is critical for proper development of the mouse placental vasculature

status: Public on Feb 20 2024

city: Harbin

first: Ximeijia

last: Zhang

address: 92 Xidazhi Street

institute: Harbin Institute of technology

summary: Maternal RNA transcription plays important roles in maintaining vasculature in mouse placental development associated with regulating gene expression, imprinting status and DNA methylation in the Dlk1-Dio3 imprinted domain.

overall_design: We used Easi-CRISPR technology to insert three polyadenylation cassettes into the promoter of Gtl2 in the Dlk1-Dio3 imprinted domain to generate Gtl2 polyA knock-in mouse model. At embryonic day 12.5 (E12.5), the placentas of paternally Gtl2 polyA knock-in (PKI), maternally Gtl2 polyA knock-in (MKI), homozygous (HOMO) and wild-type (WT) mice were selected to do the RNA-sequencing.

first: Qiong

last: Wu


title: Myb overexpression synergizes with loss of Pten and is a dependency factor and therapeutic target in T-cell acute lymphoblastic leukemia

city: Ghent

first: Bruno

last: Palhais

address: Corneel Heymanslaan 10

department: Department of Biomolecular Medicine

country: Belgium

institute: Ghent University

summary: T-lineage acute lymphoblastic leukemia (T-ALL) is an aggressive hematological malignancy that accounts for 10%–15% of pediatric and 25% of adult ALL cases. Although the prognosis of T-ALL has improved over time, the outcome of T- ALL patients with primary resistant or relapsed leukemia remains poor. Therefore, further progress in the treatment of T-ALL requires a better understanding of its biology, and the development of more effective precision oncologic therapies. The proto-oncogene MYB is highly expressed in diverse hematologic malignancies, including T-ALLs with genomic aberrations that further potentiate its expression and activity. Previous studies have associated MYB with a malignant role in pathogenesis of several cancers. However, its role in the induction and maintenance of T-ALL remains relatively poorly understood. In this study, we found that increased copy number of MYB is associated with higher MYB levels, and might be associated with inferior event-free survival of pediatric T-ALL patients. Using our previously described conditional Myb overexpression mice, we generated two distinct MYB-driven T-ALL mouse models. We demonstrated that the overexpression of Myb synergizes with Pten deletion, but not with the overexpression of Lmo2, to accelerate the development of T-cell lymphoblastic leukemias. We also showed that MYB is a dependency factor in T-ALL, since RNA interference of Myb blocked cell cycle progression and induced apoptosis in both human and murine T-ALL cell lines. Finally, we provide preclinical evidence that targeting the transcriptional activity of MYB can be a useful therapeutic strategy for the treatment of T-ALL.

overall_design:
To investigate the role of MYB in tumor maintenance, we performed doxycycline-inducible knockdown of Myb in vitro in two primary murine T-ALL cell line MyPL1.
We crossed the conditional R26-Myb model with the spontaneous T-ALL Pten/Lck-Cre mouse model, to obtain R26-Myb/Pten/LckCre mice, that overexpress Myb and have Pten loss, specifically in the T-cell compartment. We derived a primary murine T-ALL line from the obtained tumors from these R26-Myb/Pten/LckCre mice. This cell line was named MyPL1.
Next, we transduced MyPL1 with an lentiviral vector that contains an inducuble hairpin against Myb and an eGFP reporter. After transduction and GFP sorting, the parental cell line iMyb MyPL1 was established.
We performed gene expression profiling analysis (RNA-seq) upon knockdown of Myb in the primary murine T-ALL cell line iMyb MyPL1 by treating it for four days with 1 µg/mL of doxycycline (DOX) or not (control). Samples were collected at day 1, 2, 3 and 4. Four replicates were used per condition.

first: André

last: Almeida

first: Sara

last: T’Sas

first: Luca

last: Pagliaro

first: Igor

last: Fijalkowski

first: Wouter

last: Sleeckx

first: Hannah

last: Van Steenberge

first: Rafaella

last: Zamponi

first: Béatrice

last: Lintermans

last: Van Loocke

first: Alexandra

last: Reekmans

first: Valentina

last: Bardelli

first: Lisa

last: Demoen

first: Lindy

last: Reunes

first: Dieter

last: Deforce

first: Filip

last: Van Niewerburgh

first: Alex

last: Kentsis

first: Panagiotis

last: Ntziachristos

first: Nadine

last: Van Roy

first: Barbara

last: De Moerloose

first: Cristina

last: Mecucci

first: Roberta

last: La Starza

first: Giovanni

last: Roti

first: Steven

last: Goossens

first: Pieter

last: Van Vlierberghe

first: Tim

last: Pieters


title: Touch receptor end-organ innervation and function requires sensory expression of the transcription factor Meis2

city: Lyon

first: Kiran

last: Padmanabhan

address: 32-34 avenue Tony Garnier

department: IGFL

institute: ENS-Lyon

summary: To better understand the molecular changes underlying tactile defects in Meis2 mutant mice, we performed bulk RNAseq analysis on Dorsal Root Ganglia (DRG) dissected form WT, Isl1Cre/+ and Isl1Cre/+::Meis2LoxP/LoxP E18.5 embryos

overall_design: Comparative gene expression profiling analysis of RNA-seq data for DRG WT, Isl1Cre/+ and Isl1Cre/+::Meis2LoxP/LoxP E18.5 embryos

first: Kevin

last: Tartour

first: Patrick

last: Carroll

first: Frédéric

last: Marmigère


title: Effects of a humanized CD47 antibody and SIRPα on triple negative breast carcinoma stem cells

city: Bethesda

first: Thomas

middle: Joshua

last: Meyer

state: Maryland

address: 41 Center Drive, Building 41, Room B620

department: National Cancer Institute

institute: National Institutes of Health

summary: Signal regulatory protein alpha (SIRPα, designated CD172a), also called SHPS-1 (SHP substrate 1) binds to CD47, a receptor for Thromobospondin-1 (TSP1). To block CD47-SIRP interaction, several CD47 blocking agents are in clinical trials. The purpose of this project is to explore the effects of SIRPFc signaling on bCSCs (breast cancer stem cells) derived from MDA-MB- 231 cells, when bCSCs were treated with either SIRPFc or CD47 blocking antibody CC90002 from Celgene Corporation.

overall_design: MDA-MB-231 were cultured routinely as described earlier(PMID: 26840086).  MDA-MB-231 cells were cultured 72h using Aggrewell media from stem cell technologies according to manufacture instructions. The cells were treated with SIRPα-Fc or CD47 blocking antibody CC90002 (Celgene Corporation) for 72hrs. The Total RNA was extracted using ISOLATE II RNA Mini Kit from BIOLINE and RNA integrity and quantification was measured using RNA-Bio analyzer.

first: Sukhbir

last: Kaur

first: Maggie

last: Cam

first: David

last: Roberts


title: Preclinical Optimization of the PI3K/Akt inhibitor Paxalisib for the Treatment of Diffuse Midline Glioma [ATAC-Seq]

city: Callaghan

first: Dylan

last: Kiltschewskij

address: Room MS616, Level 6, Medical Sciences Building, University Drive

department: School of Biomedical Sciences and Pharmacy

institute: The University of Newcastle

summary: Diffuse midline glioma (DMG) is a uniformly fatal pediatric, adolescent, and young adult cancer diagnosed in the midline structures of the brain. PI3K/Akt signaling is an overarching contributor to the poor outcomes of DMG patients due to their dependance on insulin and recurring mutations and amplifications in PI3K/Akt genes. Paxalisib (GDC-0084) is a potent PI3K/Akt inhibitor developed to penetrate the brain’s protective blood-brain barrier (BBB). We performed paxalisib regimen optimization by assessment of blood glucose levels, analysis in vivo pharmacokinetics/pharmacodynamics properties, and employed DMG patient derived xenograft (PDX) mouse models to determine preclinical efficacy. To identify novel combination strategies, we conducted high-resolution quantitative phosphoproteomics of DMG cells treated with paxalisib. Elevated blood glucose levels promoting hyperglycemia was seen in mice using paxalisib 10 mg/kg/day (~mouse equivalent human maximum tolerated dose- NCT03696355). Whereas 5 mg/kg/day, or 5mg/kg/b.i.d. (twice daily) non-significantly increased blood glucose levels compared to controls. Pharmacokinetic analysis of mouse tissues showed 5 mg/kg/b.i.d. increased paxalisib acumination in the brainstem, suppressing PI3K/Akt signaling to significantly extend the survival of DMG PDX models compared to all other regimens; a survival benefit amplified when combined with the anti-glycemic therapy metformin. Phosphoproteomic profiling identified increased Protein kinase C (PKC) signaling following paxalisib treatment. The combination of paxalisib and enzastaurin (PKC inhibitor) synergistically extended the survival of PDX models. Our optimized dosing regimen increased the preclinical benefits of paxalisib, with the combination of paxalisib with metformin, or paxalisib with enzastaurin, heralding rationally designed combination strategies for the treatment of DMG.

overall_design: Profiling of transposase-accessible chromatin regions amongst RA055 diffuse intrinsic pontine glioma (DIPG) cells, xenografted into the pontine region of mice treated with paxalisib, enzastaurin or metformin in varying combinations.

first: Ryan

last: Duchatel

first: Evangeline

last: Jackson

first: Izac

last: Findlay

first: Sandra

last: Laternser

first: Abdul

last: Mannan

first: Padraic

last: Kearney

first: M

last: Jamaluddin

first: Dilana

last: Staudt

first: Zacary

last: Germon

first: Ameha

last: Woldu

first: Alicia

last: Douglas

first: Sarah

last: Parackal

first: Elizabeth

middle: E

last: Manning

first: Christopher

last: Dayas

first: Heather

middle: C

last: Murray

last: Skerrett-Byrne

first: Brett

last: Nixon

first: Maria

last: Tsoli

last: Ziegler

first: Murray

last: Cairns

first: Nicholas

last: Vitanza

first: Carl

last: Koschmann

first: Frank

last: Alvaro

last: Tinkle

first: Jason

last: Cain

first: Sabine

last: Mueller

first: Javad

last: Nazarian

first: Matthew

last: Dun


title: Prosaposin promotes neural stem cell quiescence

city: Paris

first: Hugo

last: Varet

address: 28 rue du Docteur Roux

institute: Institut Pasteur

overall_design: Refer to individual Series


title: Transcriptomic differences between juvenile and adult quiescent NSCs

summary: We generated a dataset in which we compared the bulk transcriptome of qNSCs between 1.5 and 3.5 mpf fish, stages between which deeper quiescence is progressively instated in order to find differences between deeply and shallow quiescent NSC

overall_design: To investigate transcriptomic differences between adult deeply quiescent NSCs and activated NSCs, we performed bulk RNA Seq

first: Miriam

last: Labusch

first: Emmanuel

last: Than-Trong

first: Marion

last: Coolen

first: Rachel

last: Legendre

first: Laure

last: Bally-Cuif


title: Transcriptomic differences between deeply quiescent and activated adult NSCs

summary: To identify pathways regulating NSC quiescence, with a possible link to quiescence depth, we used double transgenic Tg(her4:drfp);Tg(mcm5:gfp) fish and paradigms predicted to highlight deep vs shallower quiescence.  In adult fish (3 month-post-fertilization -mpf-), we performed bulk RNA sequencing on FACS sorted RFPhigh,GFPneg qNSCs (expressing strongly her4, signing NSCs transcriptionally remote from activation), and activated NSCs.


title: Bacterial single cell RNA-seq unveils cyclic-di-GMP as an antitoxin critical for antibiotic tolerance in biofilm.

city: Wuhan

first: Xiaodan

last: Yan

state: Hubei Province

address: Donghu Road, No. 115, Wuchang District,

department: Medical Research Institute

institute: Wuhan University

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

sample_organism: Escherichia coli str. K-12 substr. MG1655

overall_design:
Refer to individual Series

** The submitter states that the study's data have undergone significant changes and are no longer accurately reflected in SuperSeries GSE239505 [Feb 20, 2024]. The correct data are in SuperSeries GSE260458. **


title: Bacterial single cell RNA-seq unveils cyclic-di-GMP as an antitoxin critical for antibiotic tolerance in biofilm [scRNA-seq]

summary: Biofilms are heterogeneous bacterial communities featured by high persister prevalence, responsible for antibiotic tolerance. However, the mechanisms underlying persister formation within biofilms remained ambiguous. Here, by developing and utilizing a ribosomal RNA depleted bacterial single-cell RNA-seq method, RiboD-mSPLiT, we resolved biofilm heterogeneity and discovered pdeI as a marker gene for persister subgroup within biofilms. Remarkably, our findings elucidated that PdeI upregulates cellular levels of c-di-GMP, which acts as an antitoxin to modulate the toxicity of toxin protein HipH. HipH localizes on nucleoid and functions as a potent DNase, inducing cells into a viable but non-culturable state. Conversely, c-di-GMP interacts with HipH, reducing its genotoxic effects and enabling cells to enter a persister state, resulting in drug tolerance. Importantly, by targeting this toxin-antitoxin system, we repressed drug tolerance in Uropathogenic Escherichia coli infections, offering promising therapeutic strategies against chronic and relapsing infections.

platform_organism: Escherichia coli str. K-12 substr. MG1655

overall_design:
we performed a new single-cell library construction method for three species of bacteria: Escherichia coli MG1655, Pseudomonas aeruginosa PAO1, Staphylococcus aureus 25923 and verified the effect of different treatments during library construction on library data. Then we analysed two E.coli single-cell sequencing datas, because we found that by cluster analysis we can find biofilm's marker gene

** The submitter states that the study's data have undergone significant changes and are no longer accurately reflected in SuperSeries GSE239505 [Feb 20, 2024]. The correct data are in SuperSeries GSE260458. **


title: Bacterial single cell RNA-seq unveils cyclic-di-GMP as an antitoxin critical for antibiotic tolerance in biofilm [ChIP-seq]

overall_design:
Chromatin Immunoprecipitation DNA-sequencing (Chip-seq) is performed in overexpression of HipH in E.coli with or without C-di-Gmp(CDG)

** The submitter states that the study's data have undergone significant changes and are no longer accurately reflected in SuperSeries GSE239505 [Feb 20, 2024]. The correct data are in SuperSeries GSE260458.  GSE260458 does not include Chip-seq data.  **


title: Preclinical Optimization of the PI3K/Akt inhibitor Paxalisib for the Treatment of Diffuse Midline Glioma

first: Dylan

last: Kiltschewskij

overall_design: Comparative gene expression profiling of the SU-DIPG-VI diffuse intrinsic pontine glioma cell line treated with Paxilisb or DMSO at multiple time points via BRB-seq.

first: Ryan

last: Duchatel

first: Evangeline

last: Jackson

first: Izac

last: Findlay

first: Sandra

last: Laternser

first: Abdul

last: Mannan

first: Padraic

middle: S

last: Kearney

first: M

last: Jamaluddin

first: Dilana

last: Staudt

first: Zacary

last: Germon

first: Ameha

last: Woldu

first: Alicia

last: Douglas

first: Sarah

last: Parackal

first: Elizabeth

last: Manning

first: Christopher

last: Dayas

first: Heather

last: Murray

first: David

last: Skerrett-Byrne

first: Brett

last: Nixon

last: Tsoli

last: Ziegler

middle: L


title: Effect of global translation initiation inhibition associated to glucose starvation on cytoplasmic lncRNAs levels

first: Maxime

last: Wery

address: 26 rue d'Ulm

institute: Institut Curie

summary: To analyze the effect of global translation initiation inhibition associated to glucose deprivation on cytoplasmic lncRNAs levels, we performed RNA-Seq using WT, xrn1-delta and upf1-delta cells grown in glucose-containing complete synthetic medium (CSM) and then shifted for 16 min in glycerol- and ethanol-containing medium. In parallel, control cells were maintained for the same time in glucose-containing CSM. For the WT strains, we also included a treatment of 15 min with CHX (100 μg/ml final concentration) or an equal volume of DMSO (Mock).

overall_design: Strand-specific total RNA-seq (2 biological replicates per condition).

first: Sara

last: ANDJUS

first: Ugo

last: SZACHNOWSKI

first: Nicolas

last: VOGT

first: Isabelle

last: HATIN

first: Chris

last: PAPADOPOULOS

first: Anne

last: LOPES

first: Olivier

last: NAMY

last: WERY

first: Antonin

last: MORILLON


title: Translational landscape of Xrn1-sensitive lncRNAs in yeast

summary: To define the translational landscape of Xrn1-sensitive lncRNAs in yeast, we performed Ribo-Seq in WT and upf1 mutant cells, in native conditions or upon treatment with translation elongation inhibitor (cycloheximide).

overall_design: Ribo-seq was performed on WT and upf1 mutant yeast cells, treated or not with cycloheximide, with 2 biological replicates per condition.


title: The Role of microRNAs in Defining LSECs Cellular Identity and in Regulating F8 Gene Expression

status: Public on Feb 19 2024

city: Bonn

first: Muhammad Ahmer

last: Jamil

state: NRW

address: Sigmund-Freud Str. 25

department: Institute of experimental haematology and transfusion medicine

institute: University Clinic Bonn

summary: Coagulation Factor VIII (FVIII) plays a pivotal role within the coagulation cascade, and deficiencies in its levels, as seen in Hemophilia A, can lead to significant health implications. Liver sinusoidal endothelial cells (LSECs) are the main producers and contributors of FVIII in blood, a fact we have previously elucidated through mRNA expression profiling when comparing these cells to other endothelial cell types. Our current investigation delves into small microRNAs, analyzing their distinct expression patterns across various endothelial cells and hepatocytes. The outcome of this exploration underscores the discernible microRNA expression differences that set LSECs apart from both hepatocytes (193 microRNAs at p < 0.05) and other endothelial cells (72 microRNAs at p < 0.05). Notably, the 134 and 35 overexpressed microRNAs in LSECs compared to hepatocytes and other endothelial cells, respectively, shed light on the unique functions of LSECs in the liver. Our investigation identified a panel of 10 microRNAs (miR-429, miR-200b-3p, miR-200a-3p, miR-216b-5p, miR-1185-5p, miR-19b-3p, miR-192-5p, miR-122-5p, miR-30c-2-3p, and miR-30a-5p) that distinctly define LSEC identity. Furthermore, our scrutiny extended to microRNAs implicated in F8 regulation, revealing a subset - miR-122-5p, miR-214-3p, miR-204-3p, and miR-2682-5p - whose expression intricately correlates with F8 expression within LSECs. This microRNA cohort emerges as a crucial modulator of F8, both directly through suppression and indirect effects on established F8-related transcription factors. The above miRNA emerged as potential targets for innovative therapies in Hemophilia A patients.

overall_design: Comparison of microRNAs profiling from 3 primary liver sinusoidal endothelial cells with other primary endothelial cells including 3 human cardiac microvascular endothelial cells, 3 human pulmonary arterial endothelial cells, and 3 human pulmonary microvascular endothelial cells, and also against 3 hepatocytes

first: Muhammad

first: Osman

last: El-Maarri


title: Cytoplasmic lncRNAs accumulate upon ANS-induced translation elongation inhibition

summary: To investigate the role of translation in the decay of cytoplasmic lncRNAs, we performed RNA-Seq in WT and upf1-delta yeast cells, treated or not with CHX.

overall_design: Strand-specific total RNA-seq in control (DMSO) and ANS-treated WT and upf1 mutant cells (2 biological replicates per condition).


title: Pervasive translation of Xrn1-sensitive unstable long non-coding RNAs in yeast

summary: Despite being predicted to lack coding potential, cytoplasmic long non-coding (lnc)RNAs can associate with ribosomes. However, the landscape and biological relevance of lncRNAs translation remains poorly studied. In yeast, cytoplasmic Xrn1-sensitive lncRNAs (XUTs) are targeted by the Nonsense-Mediated mRNA Decay (NMD), suggesting a translation-dependent degradation process. Here, we report that XUTs are pervasively translated, which impacts their decay. We show that XUTs globally accumulate upon translation elongation inhibition, but not when initial ribosome loading is impaired. Ribo-Seq confirmed ribosomes binding to XUTs and identified ribosome-associated 5’-proximal small ORFs. Mechanistically, the NMD-sensitivity of XUTs mainly depends on the 3’-untranslated region length. Finally, we show that the peptide resulting from the translation of an NMD-sensitive XUT reporter exists in NMD-competent cells. Our work highlights the role of translation in the post-transcriptional metabolism of XUTs. We propose that XUT-derived peptides could be exposed to the natural selection, while NMD restricts XUTs levels.


title: Gene expression profile of submandibular gland from IgG4 related disease patients at a single cell level.

city: Chiba

first: Shigeru

last: Tanaka

address: 1-8-1 Inohana

department: Allergy and Clinical Immunology

country: Japan

institute: Chiba University

summary: IgG4-related disease (IgG4-RD) is an autoimmune disease with an unknown etiology. In this study, we focused on non-hematopoietic cells in the submandibular gland of IgG4-RD patients. Through single-cell RNA sequencing, our aim was to unravel the contributions of these cells to the development and progression of IgG4-RD.

overall_design: CD45– cells from the submandibular glands of IgG4-RD patients were sorted using FACS and subsequently underwent single-cell RNA-sequencing utilizing the 10X Genomics platform. As a comparative control, cells from the submandibular glands of neck cancer patients were also included in the analysis.

first: Arifumi

last: Iwata

first: Masahiro

last: Kiuchi

first: Kei

last: Ikeda


title: Bacterial single cell RNA-seq unveils cyclic-di-GMP as an antitoxin critical for antibiotic tolerance in biofilm [RNA-seq]

first: Xiaodan

last: Yan

overall_design:
we performed gene experssion profiling analysis using data obtained from RNA-seq of exponential growth phase E.coli. Then we analysed consistency of RNA-seq data with single-cell sequencing data.

** The submitter states that the study's data have undergone significant changes and are no longer accurately reflected in SuperSeries GSE239505 [Feb 20, 2024]. The correct data are in SuperSeries GSE260458. **


title: Single-nucleus RNA-seq characterizes the cell types along the neuronal lineage in the adult human subependymal zone

city: Nijmegen

first: Sofia

last: Puvogel

address: Geert Grooteplein Zuid 10

country: Netherlands

institute: RadboudUMC

summary: The subependymal zone (SEZ), also known as the subventricular zone (SVZ), constitutes a neurogenic niche that persists during post-natal life. To investigate the cellular diversity of this brain region during human adulthood, we characterized the complete cellular niche of the adult human SEZ by single-nucleus RNA sequencing (snRNAseq), in youth and middle-aged adults.

overall_design: Single nuclei were isolated from SEZ frozen post-mortem tissue from 4 young (16-22 years) and 4 middle-aged (44-53 years) adults. DAPI positive events were collected by FACS and subjected to snRNA.

first: Sofía

first: Astrid

last: Alsema

first: Hayley

last: North

first: Maree

last: Webster

first: Cynthia

last: Weickert

first: Bart

last: Eggen


title: miRNA expression of papillary renal neoplasm with reverse polarity  (PRNRP) cases

status: Public on Feb 18 2024

city: San Sebastian

first: Stéphane

last: Nemours

state: Guipúzcoa

address: Paseo Dr. Begiristain, s/n

institute: Biogipuzcoa

summary: Between 80% and 90% of renal carcinomas are either clear cell renal cell carcinoma or papillary RCC  although there are at least 20 other distinct forms of RCC recognised by the World Health Organization (WHO). Emerging or provisional entities have been considered as variants of PRCC, including papillary renal neoplasm with reversed polarity (PRNRP).  However, the molecular basis of PRNRP, and miRNA expression profile, is unknown. We used microarray analysis to elucidate the non-coding RNA (ncRNA)  profiles of 10 PRNRP cases and compared them with other renal neoplasms. Cases were only considered for this study after fulfilment of strict inclusive histological and immunohistochemical criteria. We used Affymetrix miRNA v.4.0 arrays to elucidate the expression of these samples.

overall_design: Samples were extracted from macrodisected FFPE slides and purified using the Recoverall kit from Ambion

first: STÉPHANE

last: NEMOURS

first: MARÍA

last: ARMESTO

last: ARESTÍN

first: CLAUDIA

last: MANINI

first: DORIANA

last: GIUSTETTO

first: MARIS

last: SPERGA

first: KRISTYNA

last: PIVOVARCIKOVA

first: DELIA

last: PÉREZ-MONTIEL

first: ONDREJ

last: HES

first: MICHAL

last: MICHAL

first: JOSÉ

middle: I

last: LÓPEZ

first: CHARLES

last: LAWRIE


title: Cytoplasmic lncRNAs accumulate upon CHX-induced translation elongation inhibition

first: Maxime

last: Wery

overall_design: Strand-specific total RNA-seq in control (DMSO) and CHX-treated WT and upf1 mutant cells (2 biological replicates per condition).

first: Sara

last: ANDJUS

first: Ugo

last: SZACHNOWSKI

first: Nicolas

last: VOGT

first: Isabelle

last: HATIN

first: Chris

last: PAPADOPOULOS

first: Anne

last: LOPES

first: Olivier

last: NAMY

last: WERY

first: Antonin

last: MORILLON


title: Large-scale bioreactor production of extracellular vesicles from mesenchymal stromal cells for treatment of acute radiation syndrome

status: Public on Feb 17 2024

city: Madison

first: Sean

last: McIlwain

state: WI

address: 1111 Highland Avenue

institute: University of Wisconsin

summary: Background: Hematopoietic acute radiation syndrome (H-ARS) occurring after exposure to ionizing radiation damages bone marrow (BM) causing cytopenias, increasing susceptibility to infections and death. We and others have shown that cellular therapies like human mesenchymal stromal cells (MSCs), or monocytes/macrophages educated ex-vivo with extracellular vesicles (EVs) from MSCs were effective in a lethal H-ARS mouse model. However, given the complexity of generating cellular therapies and the potential risks of using allogeneic products, development of an “off-the-shelf” cell-free alternative like EVs may have utility in conditions like H-ARS that require rapid deployment of available therapeutics. The purpose of this study was to determine the feasibility of producing MSC-derived EVs at large scale using a bioreactor and assess critical quality control attributes like identity, sterility, and potency in educating monocytes and promoting survival in a lethal H-ARS mouse model. Methods: EVs were isolated by ultracentrifugation from unprimed and liposaccharide (LPS)-primed MSCs grown at large scale using a hollow fiber bioreactor and compared to a small scale system using flasks. The physical identity of EVs included a time course assessment of particle diameter, yield, protein content and surface marker profile by flow-cytometry. Comparison of the RNA cargo in EVs was determined by RNA-seq. Capacity of EVs to generate exosome educated monocytes (EEMos) was determined by qPCR and flow cytometry, and potency was assessed in vivo using a lethal ARS model with NSG mice. Results: Physical identity of EVs at both scales were similar but yields by volume were up to 38-fold more using a large-scale bioreactor system. RNA-seq indicated that flask EVs showed upregulated let-7 family and miR-143 micro-RNAs. EEMos educated with LPS-EVs at each scale were similar, showing increased gene expression of IL-6, IDO, FGF-2, IL-7, IL-10, and IL-15 and immunophenotyping consistent with a PD-L1 high, CD16 low, and CD86 low cell surface expression. Treatment with LPS-EVs manufactured at both scales were effective in the ARS model, improving survival and clinical scores through improved hematopoietic recovery. EVs from unprimed MSCs were less effective than LPS-EVs, with flask EVs providing some improved survival while bioreactor EVs provide no survival benefit. Conclusions: LPS-EVs as an effective treatment for H-ARS can be produced using a scale-up development manufacturing process, representing an attractive off-the-shelf, cell-free therapy.

overall_design: RNA-seq was performed on flask-scale EVs isolated from six human MSCs isolates (Flask_Replicate1 to Flask_Replicate6) and LPSEVs from subset of 3 MSC isolates (Bioreactor_Replicate1 to Bioreactor_Replicate3) of that group. RNA-seq was also performed on three technical replicates of the bioreactor-scale EVs (96H Bioreactor) from MSCs (isolate B). RNA sequencing (RNA-seq) was performed by Systems Biosciences (Palo Alto, CA USA).

first: John

last: Kink

first: Michael

last: Bellio

first: Matthew

last: Forsberg

first: Alexandra

last: Lobo

first: Anna

last: Thickens

first: Bryson

last: Lewis

first: Irene

last: Ong

first: Aisha

last: Khan

first: Christian

last: Capitini

first: Peiman

last: Hematti


title: ZMYND8 is a negative regulator of ferroptosis in BCSCs

city: Dallas

first: Maowu

last: Luo

state: TX

address: 5323 Harry Hines Blvd.

institute: UT Southwestern Medical Center

summary: ZMYND8 Protects Breast Cancer Stem Cells against Oxidative Stress and Ferroptosis through Activation of NRF2

overall_design: Parental and ZMYND8 knockout MDA-MB-231 mammospheres were subjected to NRF2 ChIP-seq.

first: Lei

last: Bao

first: Weibo


title: Mi-2β promotes immune evasion in melanoma by activating EZH2 methylation

city: kaifeng

first: Zhixiang

last: Xu

address: Jin Ming Avenue north section

institute: 河南大学

summary: Recent development of new immune checkpoint inhibitors has been particularly successfully in cancer treatment, but still the majority patients fail to benefit. Converting resistant tumors to immunotherapy sensitivity will provide a significant improvement in patient outcome. Here we identify Mi-2β as a key melanoma-intrinsic effector regulating the adaptive anti-tumor immune response. Genetically engineered mouse melanoma studies indicate that loss of Mi-2β rescued the immune response to immunotherapy in vivo. Mechanistically, ATAC-seq indicate that Mi-2β controlled the accessibility of IFN-γ-stimulated genes (ISGs). Mi-2β bound to EZH2 and promote K510 methylation of EZH2 and subsequently activate the trimethylation of H3K27 to inhibit the transcription of ISGs. Finally, we develop an Mi-2β-targeted inhibitor, Z36-MP5, which targeted inhibition of Mi-2β ATPase activity and recovered ISG transcription. Consequently, Z36-MP5 efficiently induce a response to immunotherapy in otherwise resistant melanomas. Our work provides a potential therapeutic strategy to convert immunotherapy resistant melanomas to sensitive ones.

overall_design: Assay for transposase-accessible chromatin with high-throughput sequencing (ATAC-seq) indicate that Mi-2β controlled the accessibility of IFN-γ-stimulated genes (ISGs). Mi-2β bound to EZH2 and promote K510 methylation of EZH2 and subsequently activate the trimethylation of H3K27 to inhibit the transcription of ISGs.

first: Cang

last: Li

first: Yujia

first: Zhi-Xiang

first: Yongping

last: Jian


title: Gene expression of papillary renal neoplasm with reverse polarity  (PRNRP) cases + PRCC cases

first: Stéphane

last: Nemours

summary: Between 80% and 90% of renal carcinomas are either clear cell renal cell carcinoma or papillary RCC  although there are at least 20 other distinct forms of RCC recognised by the World Health Organization (WHO). Emerging or provisional entities have been considered as variants of PRCC, including papillary renal neoplasm with reversed polarity (PRNRP).  However, the molecular basis of PRNRP is unknown. We used microarray analysis to elucidate the gene profile of 10 PRNRP cases and an additional 7 PRCC cases. Cases were only considered for this study after fulfilment of strict inclusive histological and immunohistochemical criteria. We used Affymetrix Clariom D human arrays to elucidate the expression of these samples.

first: STÉPHANE

last: NEMOURS

first: MARÍA

last: ARMESTO

last: ARESTÍN

first: CLAUDIA

last: MANINI

first: DORIANA

last: GIUSTETTO

first: MARIS

last: SPERGA

first: KRISTYNA

last: PIVOVARCIKOVA

first: DELIA

last: PÉREZ-MONTIEL

first: ONDREJ

last: HES

first: MICHAL

last: MICHAL

first: JOSÉ

last: LÓPEZ

first: CHARLES

last: LAWRIE


title: Oncopig and Human Bladder Cancer Cell Lines: Control vs Gemcitabine Treated

status: Public on Feb 16 2024

city: Chicago

first: Kyle

last: Schachtschneider

state: IL

address: 2201 West Campbell Park Drive

institute: Sus Clinicals Inc

summary: Transcriptional profiling of Oncopig and human bladder cancer cell lines comparing control untreated cells to cell treated with gemcitabine for 48 hours. Goal was to compare similar transcriptional alterations in response to gemcitabine treatment across both species

sample_organism:
Homo sapiens
Sus scrofa

platform_organism:
Homo sapiens
Sus scrofa

overall_design: Two-condition experiment, control vs gemcitabine treated cells. Biological replicates: 3 control replicates, 3 treated replicates for both species.

first: Tiago

last: Collares

first: Lawrence

last: Schook

first: Natalia

last: Segatto


title: Transcription of endogenous retroviruses in pre-senescent cells contributes to the accumulation of double-stranded RNAs that trigger an anti-viral response that reinforces senescence

city: Perugia

first: Elisabetta

last: Albi

state: Italy

address: Via Romana

department: Department of Pharmaceutical Sciences

country: Italy

institute: Università degli studi di Perugia

summary: An important epigenetic switch marks the onset and maintenance of senescence. This allows transcription of the genetic programs that arrest the cell cycle and alter the microenvironment. Transcription of endogenous retroviruses (ERVs) is also a consequence of this epigenetic switch. In this manuscript, we have identified a group of ERVs that are epigenetically silenced in proliferating cells but are upregulated during replicative senescence or during various forms of oncogene-induced senescence, by RAS, Akt, or HDAC4 depletion. In an HDAC4 model of OIS, removal of the repressive histone mark H3K27me3 is the plausible mechanism that allows the transcription of intergenic ERVs during senescence. We have shown that ERVs contribute to the accumulation of dsRNAs in senescence, which can initiate the antiviral response via the IFIH1-MAVS signaling pathway and thus contribute to the maintenance of senescence. This pathway, and MAVS in particular, plays an active role in shaping the microenvironment and maintaining growth arrest, two essential features of the senescence program

overall_design: Double strand RNA immunoprecipitation from proliferating SK-LMS-1 cells and cells undergoing senescence at 96h from HDAC4 depletion. Total RNA pre-immunoprecipitation was used as input

first: Nicolò

last: Gualandi

first: Eros

last: Di Giorgio

first: Liliana

last: Ranzino

first: Vanessa

last: Tolotto

first: Emiliano

last: Dalla

first: Matteo

last: Burelli

first: Claudio

last: Brancolini


title: Screening of differentially expressed genes in LSCC cells knocking down FSCN1

city: Taiyuan

first: Liu

last: Hongliang

state: Shanxi

address: No. 56, South Xinjian Road

institute: Shanxi Medical University

type:
Expression profiling by array
Non-coding RNA profiling by array

summary: Laryngeal squamous cell carcinoma (LSCC) is a common malignant tumor with a poor prognosis. Fascin actin-bundling protein 1 (FSCN1) has been reported to play a crucial role in LSCC development and progression, but the underlying molecular mechanisms remain unknown. Here, a whole transcriptome microarray analysis was performed to screen for differentially expressed genes in FSCN1 knockdown cells. We identified 1063 differentially expressed mRNA transcripts. Functional annotation revealed that these differentially expressed genes (DEGs) were involved in multiple biological functions such as transcriptional regulation, response to radiation, focal adhesion, ECM-receptor interaction, steroid biosynthesis, and others. Through co-expression and protein-protein interaction analysis, we linked FSCN1 to novel functions, including defense response to virus and steroid biosynthesis.

overall_design: Three independent siRNA transfections were performed to generate FSCN1 knockdown and control TU-177 cells, followed by total RNA extraction and integrity examination.

first: Hongliang

last: Liu