title: An anciently diverged family of RNA binding proteins maintain correct splicing of ultra-long exons through cryptic splice site repression [iCLIP-seq]

status: Public on Sep 28 2023

city: Newcastle upon Tyne

first: Graham

last: Smith

address: Framlington Place

department: Bioinformatics Support Unit

institute: Newcastle University

summary: We previously showed that the germ cell specific nuclear protein RBMXL2 represses cryptic splicing patterns during meiosis and is required for male fertility. RBMXL2 evolved from the X-linked RBMX gene, which is silenced during meiosis due to sex chromosome inactivation. It has been unknown whether RBMXL2 provides a direct replacement for RBMX in meiosis, or whether RBMXL2 evolved to deal with the transcriptionally permissive environment of meiosis. Here we find that RBMX primarily operates as a splicing repressor in somatic cells, and specifically regulates a distinct class of exons that exceed the median human exon size. RBMX protein-RNA interactions are enriched within ultra-long exons, particularly within genes involved in genome stability, and repress the selection of cryptic splice sites that would compromise gene function. These similarities in overall function suggested that RBMXL2 might replace the function of RBMX during meiosis. To test this prediction we carried out inducible expression of RBMXL2 and the more distantly related RBMY protein in somatic cells, finding each could rescue aberrant patterns of RNA processing in response to RBMX depletion. The C-terminal disordered domain of RBMXL2 is sufficient to rescue proper splicing control after RBMX depletion. Our data indicate that RBMX and RBMXL2 have parallel roles in somatic tissues and the germline that must have have been conserved over at least 200 million years of mammalian evolution. We propose RBMX family proteins are particularly important for the splicing inclusion of ultra-long exons because these would be particularly susceptible to disruption by cryptic splice site selection.

overall_design: Individual-nucleotide resolution UV crosslinking and immunoprecipitation (iCLIP-seq) of RBMX protein done in triplicate

first: Chileleko

last: Siachisumo

first: Sara

last: Luzzi

first: Saad

last: Aldalaqan

first: Gerald

last: Hysenaj

first: Caroline

last: Dalgliesh

first: Kathleen

last: Cheung

first: Matthew

last: Gazzara

first: Ivaylo

last: Yonchev

first: Katherine

last: James

first: Mahsa

last: Chadegani

first: Ingrid

last: Ehrmann

first: Simon

last: Cockell

first: Jennifer

last: Munkley

first: Stuart

middle: A

last: Wilson

first: Yoseph

last: Barash

last: Elliott


title: Nanobodies agains Sars Cov 2 Nsp9 protein protects cells from virus infection

status: Public on Oct 10 2023

city: Abu Dhabi

first: Piergiorgio

last: Percipalle

state: Abu Dhabi

address: Saadiyat Campus, Abu Dhabi

department: Biology Department, Science Division

country: United Arab Emirates

institute: New York University Abu Dhabi

type: Expression profiling by high throughput sequencing

summary: Nanobodies are emerging as ideal instruments for drug design and several have recently been created to block SARS-Cov-2 entry in the host cell by targeting surface-exposed Spike protein. However, due to the high frequency of mutations that affect Spike, these nanobodies may not efficiently target Spike during viral entry. Here we have established a pipeline that instead targets highly conserved viral proteins that are made only after viral entry into the host cell when the SARS-Cov-2 RNA-based genome is translated. As proof of principle, we designed nanobodies against the SARS-CoV-2 non-structural protein Nsp9, required for replication of the viral genome. To find out if this strategy efficiently blocked viral replication, one of these anti-Nsp9 nanobodies, 2NSP23, previously characterized using immunoassays and NMR spectroscopy for epitope mapping, was encapsulated into lipid nanoparticles (LNP) as mRNA. We show that this nanobody, hereby referred to as LNP-mRNA-2NSP23, is internalized and translated in HEK293 cells. We next infected HEK293-ACE2 cells subjected to LNP-mRNA-2NSP23 with multiple SARS-CoV-2 variants. Analysis of total RNA isolated form infected cells treated or untreated with LNP-mRNA-2NSP23 using qPCR and RNA deep sequencing shows that the LNP-mRNA-2NSP23 nanobody protects HEK293-ACE2 cells and suppresses replication of several SARS-CoV-2 variants. These observations indicate that following translation, the nanobody 2NSP23 inhibits viral replication by targeting Nsp9 in living cells. We propose that LNP-mRNA-2NSP23 may be translated into an innovative technology to generate novel antiviral drugs highly efficient across coronaviruses.

overall_design: RNA seq analysis of 293T cells treated with lipid nanoparticles containing control dTomato (LNP45) or Nsp9 nanobody mRNA (LNP23) which are subsequently infected with different variants of Sars Cov 2 virus

first: Tomas

last: Venit

first: Nizar

last: Drou

first: Jean-Claude

last: Twizere


title: Pachytene piRNAs govern male meiosis I by spatial restriction of gene expression (siRNA)

status: Public on Oct 14 2023

city: Houston

first: Jacob

middle: Manuel

last: Ortega

state: Texas

address: 6550 Bertner Ave

department: Genetics

country: USA

institute: MD Anderson Cancer Center

type: Non-coding RNA profiling by high throughput sequencing

summary: Pachytene piRNAs control male fertility across metazoans, yet mechanisms through which they govern meiosis I in pachytene remain unclear. We demonstrate, in C. elegans, that homolog pairing, and crossover formation are compromised in the absence of piRNA function. We identify several protein coding genes as targets of piRNAs including Polo like kinase 3 (PLK-). Pachytene piRNAs spatially restrict and exclude PLK-3 expression from meiosis I. Expansion of PLK-3 expression into the pachytene region, upon loss of piRNAs, is reflected in meiotic defects, which are partially rescued by removal of ectopic PLK-3. Pachytene piRNAs regulate PLK-3 through both translational repression and post-transcriptional degradation establishing the spatiotemporal control of gene expression. Given the conserved role of pachytene piRNAs, we propose that these mechanisms may be applicable to mammals.

overall_design: To identify differences in 22G siRNA levels mapping to protein-coding genes between wild type and prg-1 mutant adult male C. elegans, we profiled small RNA samples for piRNAs derived from animals of the following genotypes [replicates]: Wild Type [x3], prg-1(null) [x3].

first: Lamia

last: Wahba

last: Seemann

first: Andrew

last: Fire

first: Swathi

last: Arur


title: The Gene Profile of Senescent Corneal Cells

status: Public on Oct 25 2023

city: Kyoto

first: Akifumi

last: Matsumoto

state: Kyoto

address: 465 Kajii-cho, Kawaramachi-Hirokoji, Kamigyo-ku

department: Department of Ophthalmology

country: Japan

institute: Kyoto Prefectural University of Medicine

summary: To investigate the gene profiles of senescent corneal cells by X-ray exposure.

overall_design: Three biological replicates were analyzed for each of 2 conditions (untreated, irradiation)

first: Koji

last: Kitazawa

first: Kosaku

last: Numa


title: Mechanisms of response and resistance to combined decitabine and ipilimumab for advanced myeloid disease

status: Public on Oct 31 2023

city: Boston

first: Livius

last: Penter

state: MA

address: 450 Brookline Avenue

department: Medical Oncology

institute: Dana-Farber Cancer Institute

summary: The ETCTN 10026 study tested decitabine and ipilimumab for transplant-naive advanced myelodysplastic syndrome/acute myeloid leukemia and relapsed acute myeloid leukemia after allogeneic hematopoietic stem cell transplantation. Using single cell RNA sequencing, determinants of response (higher T/NK to myeloid cell ratio in responders) and resistance (insufficient clearance of AML clones) were identified and pharmacodynamics of decitabine (cytoreduction) and ipilimumab (increase in regulatory T cells) characterized.

overall_design:
Single cell RNA sequencing of unselected bone marrow-derived mononuclear cells before treatment (screening), after 1 cycle of decitabine treatment alone (end of lead-in, EOLN), after combined treatment with decitabine and ipilimumab (C1, C2, ...), and at the end of treatment (EOT).
NOTE FROM SUBMITTER: The raw data for this submission is being deposited in dbGAP under accession number phs003015.v1.

first: Jacqueline

middle: S

last: Garcia

first: Catherine

middle: J

last: Wu


title: An anciently diverged family of RNA binding proteins maintain correct splicing of ultra-long exons through cryptic splice site repression

first: Graham

last: Smith

country: United Kingdom

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

overall_design: Refer to individual Series


title: An anciently diverged family of RNA binding proteins maintain correct splicing of ultra-long exons through cryptic splice site repression [RNA-seq]

overall_design:
RNA-Seq was performed on the following samples:
MDA-MB-231 cells treated with either control siRNAs (1 + 3 biological replicates) or siRNAs targeting RBMX (1 + 3 biological replicates);
HEK293 cells treated with either control siRNAs or siRNAs targeting RBMX, half of which were treated with tetracycline to induce RBMXL2 overexpression (1 biological replicate per condition)

**Please note that no suitable processed data was generated for GSM7429573-GSM7429576 samples. The processing produced BAMs which were examined in IGV to generate the conclusions that are described in the associated publication.

first: Chileleko

last: Siachisumo

first: Sara

last: Luzzi

first: Saad

last: Aldalaqan

first: Gerald

last: Hysenaj

first: Caroline

last: Dalgliesh

first: Kathleen

last: Cheung

first: Matthew

middle: R

last: Gazzara

first: Ivaylo

middle: D

last: Yonchev

first: Katherine

last: James

first: Mahsa

middle: K

last: Chadegani

first: Ingrid

last: Ehrmann

first: Simon

last: Cockell

first: Jennifer

last: Munkley

first: Stuart

last: Wilson

last: Barash

first: David

last: Elliott


title: Transcriptomic analysis of the effect of Sfp1 depletion

status: Public on Sep 21 2023

city: Burjassot

first: Jose

middle: E.

last: Perez-Ortin

state: Valencia

address: Dr. Moliner 50

department: Bioquimica y Biologia Molecular

country: Spain

institute: Universitat de Valencia

summary: The effect of Sfp1 depeltion at transcriptional level was investigated by construting a AID-Sfp1 strain (Auxin sensitive degron) that allowed to shutoff the Sfp1 expression and analyze the primary effects on synthesis rates (SR) and mRNA levels (RA) genome-wide. mRNA stabilities can be calculated as RA /SR for each gene in all samples.

overall_design: For the degron experiment, the auxin degron strain (AID-Sfp1) was inoculated in YPD medium until a OD600 of 0.4 and then an aliquot was taken, corresponding to t=0. After auxin addition two more samples were taken at 20 and 60 minutes. At each time point (0, 20 and 60 minutes) Genomic Run-on (GRO) was performed, as described in (Oliete-Calvo et al., 2018), and data for SR, RA were obtained for each time point. Note that each sample record represents two (cDNA) and (GRO) replicates .

first: José

middle: E

last: Pérez-Ortín

last: García-Martínez


title: Luteolin exerts anti-tumor immunity in hepatocellular carcinoma by accelerating CD8+ T lymphocyte infiltration

status: Public on Sep 20 2023

city: tianjin

first: shijiao

last: cai

address: Qixiangtai road

country: China

institute: Tianjin Medical University

summary: We observed that luteolin effectively restrained the growth of solid tumors in the established mouse model of HCC. Expression spectrum chip sequencing showed that treatment with luteolin could promote T cell activation, cell chemotaxis and cytokine production. Furthermore, we explored the influence of luteoin on the phenotypic and functional alterations of T cells. Our findings revealed that luteolin maintained a high ratio of CD8+ T cells in the peripheral blood, spleen, and tumor tissues. Additionally, luteolin restored the cytotoxicity of tumor-infiltrating CD8+ T cells in H22 tumor-bearing mice. Moreover, CD8+ T cells showed stronger activation phenotypes and more production of IFN-γ, TNFα, and Granzyme B in serum. Furthermore, the co-administration of luteolin and PD-1 mAb resulted in potentiated anti-tumor effects in H22 tumor-bearing mice.These findings indicate that luteolin could exert an anti-tumor immune response by inducing CD8+ T cell infiltration and enhance the anti-tumor effects of PD-1 mAb in HCC treatment in H22 tumor-bearing mice.

overall_design: To investigate the function of luteolin on hepatocellular carcinoma, H22 cells were injected subcutaneously into BALB/c mice.200mg/kg luteolin or 0.5% carboxymethyl cellulose sodium were administered strictly once daily for 21 days in a volume of 0.2 ml when the tumor volume reached ∼50 mm3.  We then performed gene expression profiling analysis using data obtained from RNA-seq .

first: Shijiao

last: Cai

first: YiDan

last: Gou

first: Yanyan

last: Chen

first: Hengjie

last: Yuan


title: Systematic identification of RNA-binding proteins and tethered domains that activate exon splicing inclusion [eCLIP-seq]

status: Public on Sep 25 2023

city: La Jolla

first: Brian

last: Yee

state: CA

address: 9500 Gilman Dr

department: Health

institute: UCSD

summary: RNA-binding proteins (RBPs) modulate alternative splicing outcomes to determine isoform expression and cellular survival. To identify RBPs that directly drive alternative exon inclusion, we evaluated 718 human RBPs with tethered function luciferase-based splicing reporter assays to identify 58 candidates, including known splicing factors such as RBFOX and serine-arginine proteins. We performed enhanced CLIP, RNA-seq, and affinity purification-mass spectrometry to investigate a subset of the 11 candidates with no prior association with splicing. Integrative analysis of these assays indicated the surprising roles of TRNAU1AP, SCAF8, and RTCA in modulating hundreds of endogenous splicing events. We also leveraged our tethering assays and top candidates to identify potent and compact exon inclusion activation domains for splicing modulation applications. Using identified domains, we engineered programmable fusion proteins which outperformed current artificial splicing factors at manipulating inclusion of reporter and endogenous exons. Altogether, our tethering approach characterized the ability of RBPs to induce exon inclusion and yielded new molecular parts for programmable splicing control.

overall_design: eCLIP-seq with TRNAU1AP-specific antibody in HEK cells, or V5-specific antibody in HEK cells overexpressing V5-tagged targets

first: Jonathan

middle: C

last: Schmok

first: Manya

last: Jain

first: Lena

last: Street

first: Maya

middle: L

last: Gosztyla

first: Evan

last: Boyle

first: Pratibha

last: Jagannatha

first: En-Ching

last: Luo

first: Marko

last: Jovanovic

first: Gene

middle: W

last: Yeo


title: STAT3-dependent long non-coding RNA Lncenc1 contributes to ES cells pluripotency

status: Public on Sep 27 2023

city: Milan

first: Emanuele

last: Monteleone

state: Italy

address: Via Olgettina 60

country: Italy

institute: Università Vita Salute San Raffaele

summary: The self-renewal of Embryonic Stem Cells (ESCs) relies on a complex interplay of pluripotency transcription factors and their targets. LIF-activated STAT3 is a key player in regulating stemness by a number of mechanisms, including the transcriptional induction of pluripotency factors and the maintenance of a stern–like epigenetic landscape. However, not much is known about how STAT3 may be involved in the regulation of stem-cell specific non coding RNAs, an important player in the balance between pluripotency and differentiation. Here we identify in mouse ESCs a STAT3-dependent long non coding RNA, Lncenc1, which is required for pluripotency maintenance and mostly localizes to the cytoplasm. Lncenc1 acts as a positive feedback regulator of the LIF-STAT3 axis by competing for the binding of microRNA-128 to the 3’UTR of the core pluripotency factor Klf4 mRNA, enhancing its expression. Our results unveil a novel mechanism for LIF-STAT3-mediated pluripotency.

overall_design: gene expression profiling analysis of RNA-seq data for mES-E14 cells and its KD derivatives (AsoLncecn1_1,AsoLncecn1_2,shLncenc1_1,shLncenc1_2)

first: Valeria

last: Poli


title: Mouse modeling of pediatric glioma, MYCN reveals intratumoral heterogeneity including neuronal and oligodendroglial lineage signatures

city: Hamburg

first: Melanie

last: Schoof

address: Martinistr. 52

country: Germany

institute: Research Institute Childrens Cancer Center Hamburg

type: Methylation profiling by genome tiling array

sample_organism:
Homo sapiens
Mus musculus

platform_organism:
Homo sapiens
Mus musculus


title: A dynamic atlas of immunocyte migration reveals specific populations of gut-imprinted cells in distal tissues

status: Public on Sep 13 2023

first: Silvia

last: Galvan-Pena

address: 77 Avenue Louis Pasteur

department: Department of Immunology

institute: Harvard Medical School

summary: Dysbiosis in the gut microbiota impacts several systemic diseases. One possible mechanism is the migration of perturbed intestinal immunocytes to extra-intestinal tissues. Combining the Kaede photoconvertible mouse model and single-cell genomics, we generated a detailed map of migratory trajectories from the colon, at baseline and during intestinal and extra-intestinal inflammation. All colonic lineages emigrated from the colon in an S1P-dependent manner, dominated by B lymphocytes with a large continuous circulation of follicular B cells, which carried a gut-imprinted transcriptomic signature. T cell emigration was more selective, with distinct groups of RORg+ cells and IEL-like CD160+ T cells in the spleen. Gut inflammation curtailed emigration, except for DCs disseminating to lymph nodes. Colon emigrating cells distributed differentially to tumor, skin inflammation, or arthritic synovium, the former dominated by myeloid cells in a chemokine-dependent manner. These results thus reveal specific cellular trails originating in the gut, influenced by microbiota, which can shape peripheral immunity.

overall_design: We investigated the transcriptional status of colon-origin migratory immunocytes and compared it to local cells. To do so we used 7-week-old female Kaede.B6 mice, and sorted splenic CD45+ Kaede green and CD45+ Kaede red from the same mice 24hr, 48hr and 72hr post-photoconversion of the descending colon. Each sample was tagged with DNA-coded anti-CD45 hashtag antibodies (BioLegend) post-sort. Cells were encapsulated using the Chromium Single Cell 5’ v3 platform (10X Genomics).

last: Galván-Peña

first: Diane

last: Mathis

first: Christophe

last: Benoist


title: Systematic identification of RNA-binding proteins and tethered domains that activate exon splicing inclusion

status: Public on Sep 22 2023

last: Yee


title: Multifaceted anti-tumor activity of a CDK9 inhibitor in prostate cancer [RNA-seq]

city: Bedford Park

first: Luke

last: Selth

state: SA

address: Flinders Drive

department: College of Medicine and Public Health

country: Australia

institute: Flinders University

summary: Cyclin-dependent kinase 9 (CDK9) stimulates oncogenic transcriptional pathways in cancer. Here, we evaluate the activity of an orally bioavailable CDK9 inhibitor, CDKI-73, in prostate cancer, a disease characterized by aberrant activity of multiple transcriptional regulators. CDKI-73 caused inhibition of proliferation and cell death in diverse in vitro models of androgen receptor (AR)-driven and AR-independent models of castration-resistant prostate cancer (CRPC). The activity of CDKI-73 was validated in more clinically-relevant systems, including xenografts, patient-derived tumor explants and aggressive patient-derived CRPC organoids. Mechanistically, CDKI-73 inhibited CDK9-mediated phosphorylation of serine 2 on RNA polymerase II and serine 81 on AR. This resulted in reduced levels of anti-apoptotic factors and suppression of signaling pathways regulated by AR, MYC and BRD4, key drivers of dysregulated transcription in prostate cancer. CDKI-73 synergized with the BRD4 inhibitor AZD5153 in cell lines and organoid models of aggressive AR-driven and AR-independent disease. Collectively, our work provides new insights into CDK9’s oncogenic activity and reveals CDKI-73 as a promising therapeutic agent for prostate cancer, particularly aggressive, therapy-resistant subtypes.

overall_design: RNA-seq analysis of LNCaP cells following 4 hours of CDKI-73 treatment (250nM) or DMSO control.


title: Effect of knockdown of HEXB on gene expression of GSC1 cells.

status: Public on Sep 07 2023

city: shenyang

first: Xin

last: Chen

address: No. 36, Sanhao Street

institute: Shengjing Hospital Affiliated to China Medical University

summary: To explore the mechanism of HEXB regulating GBM cell glycolysis, we transcriptionally profiled endogenous HEXB-silenced GSC1 for further enrichment analysis based on down-regulated genes positively related to HEXB knockdown.

overall_design: Mechanism exploration of GSC1 cells between NC and ShHEXB based on RNA-seq data.

first: Chen

last: Zhu

first: Tianqi

last: Liu

first: Lin

last: Cheng

first: Wen

first: Peng

first: Anhua

last: Wu


title: Regulation of potassium homeostasis in Caulobacter crescentus [RNA-seq]

status: Public on Jan 19 2024

city: Namur

first: Regis

last: Hallez

address: 61 Rue de Bruxelles

country: Belgium

institute: UNamur

summary: Potassium (K+) is an essential physiological element determining membrane potential, intracellular pH, osmotic/turgor pressure, and protein synthesis in cells. Nevertheless, K+ homeostasis remains poorly studied in bacteria. Here we describe the regulation of potassium uptake systems in the oligotrophic -proteobacterium Caulobacter crescentus known as a model for asymmetric cell division. We show that C. crescentus can grow in concentrations from the micromolar to the millimolar range by essentially using two K+ transporters to maintain potassium homeostasis, the low affinity Kup and the high affinity Kdp uptake systems. When K+ is not limiting, we found that the kup gene is essential while kdp inactivation does not impact the growth. In contrast, kdp becomes critical but not essential and kup dispensable for growth in K+-limited environments. However, in the absence of kdp, mutations in kup were selected to improve growth in K+-depleted conditions, likely by improving the affinity of Kup for K+. In addition, mutations in the KdpDE two-component system, which regulates kdpABC expression, suggest that the inner membrane sensor regulatory component KdpD works as a kinase in early stages of growth and as a phosphatase to regulate transition into stationary phase. Our data also show that KdpE is not only phosphorylated by KdpD but also by another non-cognate histidine kinase. On top of this, we determined the KdpE-dependent and independent K+ transcriptome and identified the direct targets of KdpE. Together, our work illustrates how an oligotrophic bacterium responds to fluctuation in K+ availability.

overall_design: Determination of K+- and KdpE-dependent regulons in Caulobacter crescentus WT and DkdpE cells grown in minimal media M2G-K supplemented either with 5 mM or 0.025 mM K+

first: Alex

last: Quintero-Yanes

first: Loïc

last: Léger

first: Madeline

last: Collignon

first: Julien

last: Mignon

first: Aurélie

last: Mayard

first: Catherine

last: Michaux

first: Régis


title: PML modulates epigenetic composition of chromatin to regulate expression of pro-metastatic genes in triple-negative breast cancer

first: Rosa

last: Bernardi

address: via Olgettina 60

institute: San Raffaele Scientific Institute

type: Genome binding/occupancy profiling by high throughput sequencing


title: Transcriptome profiling of lettuce plants exposed to abiotic stresses

status: Public on Sep 01 2023

city: Beltsville

first: Sunchung

last: Park

state: MD

address: 10300 Baltimore ave, Bldg001

department: ARS-NEA

institute: USDA -ARS

summary: Lettuce is one of most consumed vegetables globally. This crop is susceptible to abiotic stresses. To understand the molecular mechanisms of stress response in lettuce, global transcriptome analysis was conducted. This analysis revealed distinctive temporal expression patterns among the stress-regulated genes in lettuce plants exposed to abiotic stresses

overall_design: mRNA profiles for lettuce plants exposed to cold for 0h, 4h, 24h, or 7d or to heat, drought, and salt for 0h, 5h, 24h, 48h  were generated in triplicate by Illumina RNA sequencing

first: Beiquan

last: Mou


title: RNA-seq analysis reveals potential molecular mechanism of RAD54B on cell proliferation of inflamed human dental pulp cells

status: Public on Sep 02 2023

city: Wuhan

first: Pei

last: Huang

state: Hubei

address: 237 Luoyu Road

department: School and Hospital of Stomatology

institute: Wuhan University

summary:
Purpose: To compare the transcriptional changes of genes in dental pulp tissues with different degrees of inflammatory severity and investigate the role of RAD54B in inflamed human dental pulp cells (hDPCs)
Methods: Normal, carious, and pulpitis human dental pulp tissues were collected. Total RNA extracted were subjected to RNA-sequencing and gene expression profiles were further studied by Gene Ontology (GO) and KEGG pathway analysis. DEGs (differentially expressed genes) in homologous recombination repair (HRR) were validated with qRT-PCR. The expression of RAD54B and TNF-α in human dental pulp tissues was detected by immunohistochemistry. HDPCs were cultured and RAD54B level in hDPCs was detected after LPS stimulation using western blot. CCK-8 was applied to investigate the cell proliferation of hDPCs transfected with negative control (Nc) small interfering RNA (siRNA), RAD54B siRNA, P53 siRNA or both siRNAs with or without LPS stimulation. Flow cytometry was applied to detect the cell cycle distribution, and western blot and immunofluorescence were utilized to analyze the expression of RAD54B, P53 and P21 under the above treatments. One-way and two-way ANOVA followed by LSD posttest were used for statistical analysis.
Results: RNA-sequencing results identified DEGs among three groups. KEGG pathway analysis revealed enrichment of DEGs in Replication and Repair pathway. HRR and non-homologous end joining (NHEJ) components were further verified and qRT-PCR results were basically consistent with the sequencing data. RAD54B, a HRR accessory factor highly expressed in carious and pulpitis tissues compared to normal pulp, was chosen as our gene of interest. High RAD54B expression was confirmed in inflamed human dental pulp tissues and LPS-stimulated hDPCs. Upon RAD54B knockdown, P53 and P21 expressions in hDPCs were upregulated whereas the cell proliferation was significantly downregulated, accompanied with increased G2/M phase arrest. After inhibiting P53 expression in RAD54B-knockdown hDPCs, P21 expression and cell proliferation were reversed.
Conclusions: Gene expression profiles of normal, carious and pulpitis human dental pulp tissues were revealed. HRR components was elucidated to function in dental pulp inflammation. Among HRR DEGs, RAD54B could regulate the cell proliferation of inflamed hDPCs via P53/P21 signaling. This research not only deepens our understanding of dental pulp inflammation but also provides a new insight to clarify the underlying mechanisms.

overall_design: gene profiles of human dental tissues with different degrees of inflammatory severity were analyzed by RNA-seq

first: Liuyan

last: Meng

first: Fushi

last: Wang


title: PML modulates epigenetic composition of chromatin to regulate expression of pro-metastatic genes in triple-negative breast cancer [ChIP-seq]

status: Public on Sep 11 2023

summary: The promyelocytic leukemia (PML) protein organizes nuclear aggregates known as PML nuclear bodies (PML-NBs), where many transcription factors and transcriptional regulators converge to be regulated. Specific associations of PML and PML-NBs with chromatin are described in different cell types, further implicating PML in transcriptional regulation. However, a complete understanding of the functional consequences of PML association to DNA in a cellular context where it regulates relevant phenotypes is still lacking.We examined the role of PML in chromatin association and transcription in triple-negative breast cancer (TNBC), a pathological condition where PML exerts important oncogenic functions. We find that PML associates discontinuously with large heterochromatic PML-associated domains (PADs) that contain gene-rich euchromatic sub-domains locally depleted of PML. PML promotes heterochromatic organization in PADs and expression of pro-metastatic genes embedded in these sub-domains. Importantly, this occurs outside PML-NBs, suggesting that nucleoplasmic PML exerts a cell type-relevant function of transcriptional regulation. PML also plays an indirect regulatory function in TBNC cells by promoting the expression of pro-metastatic genes outside PADs.Our findings demonstrate that PML is an important transcriptional regulator of metastasis and pro-oncogenic metagenes in TNBC cells, via distinct molecular activities that include indirect transcriptional regulation and direct epigenetic organization of heterochromatin domains that embed regions of localized transcriptional activity.

overall_design: Chromatin immunoprecipitation DNA-sequencing (ChIP-seq) for PML, LMNB1, H3K9me3, H3K27me3, H3K4me3 and H3K27ac in MDA-MB-231 cells.

first: Cristina

last: Fracassi

first: Martina

last: Ugge’

first: Mohamed

last: Abdelhalim

first: Ettore

last: Zapparoli

first: Dejan

last: Lazarevic

first: J

middle: M

last: Morelli

first: Philippe

last: Collas


title: Transcriptional differences in breast cancer cells exposed to acute versus chronic hypoxia.

city: Baltimore

first: Ines

last: Godet

address: 1650 Orleans Street, CRB1, room 128

department: Oncology

institute: Johns Hopkins University

summary: Our previous studies demonstrated that exposing  cells to acute hypoxic conditions in vitro (24 h at 1% oxygen) does not fully recapitulate exposure to intratumoral hypoxia (Godet et al., 2019). In this study, we sought to investigate whether chronic exposure to hypoxia in vitro (10 days at 1% oxygen) would better mimic the transcriptional effects of intratumoral hypoxia.

overall_design: To compare acute versus chronic hypoxic conditions, MDA-MB-231 cells were cultured for 1 or 10 days under 20% or 1% O2. To investigate the effect of reoxygenation, cells cultured for 10 days under 1% O2 were then subjected to 10 days under 20% O2. RNA was extracted using the Direct-zol miniRNA kit (Zymo) and samples with RIN>9 were submitted for library preparation, RNA sequencing and preliminary analysis.

first: Daniele

last: Gilkes


title: Effect of Serendipita indica-infection on the gene expression in wild-type and YUC9 overexpressing Arabidopsis thaliana plants

status: Public on Aug 30 2023

city: Pozuelo de Alarcón

first: Stephan

last: Pollmann

state: Madrid

address: Campus de Montegancedo, Autovia M-40 (km 38)

institute: CBGP (UPM-INIA/CSIC)

summary: The root-colonizing fungal endophyte Serendipita indica, formerly known as Piriformospora indica, is well known to promote plant biomass production and stress tolerance of its host plants. Moreover, previous studies highlighted an important impact of the fungus on auxin homeostasis during the infection of Arabidopsis thaliana plants. Auxin is a key determinant of plant growth, including the growth of the root system. Auxin overproducing mutants, like for instance YUC9oe (Hentrich et al., 2013 Plant J.), show a pronounced root phenotype that can be restored by the co-cultivation with S. indica. We here report the comparative analysis of the effect of a mock- and S. indica-infection on both wild-type Arabidopsis plants (Col-0) and YUC9 overexpressing mutants. Our data provide evidence for the induction of GRETCHEN HAGEN 3 (GH3) genes that are involved in conjugating active free indole-3-acetic acid with amino acids. The fungus triggered induction GH3s is suggested to be involved in affecting the cellular auxin homeostasis.

overall_design: To investigate differential gene expression in mock- (WOP) and S. indica-infected (WP) Arabidopsis wild-type plants (Col-0) and YUC9 overexpression mutants

first: Jesús

last: Vicente-Carbajosa


title: Mesenchymal stem cells in synovial fluid increase in number in response to synovitis and display more tissue-reparative phenotypes in osteoarthritis

status: Public on Aug 17 2023

city: Bunkyo-ku

first: Kentaro

last: Endo

state: Tokyo

address: 1-5-45 Yushima

institute: Institute of Science Tokyo

summary: To investigate whether the gene expression profiles of synovial fluid mesenchymal stem cells (SF-MSCs) from rat OA knees were favorable for endogenous cartilage repair, we performed RNA sequencing for SF-MSCs from intact knees and knees 4 weeks after the pMx and sham surgery.

overall_design: Comparative gene expression profiling analysis of RNA-seq data for SF-MSCs from intact knees and knees 4 weeks after the pMx and sham surgery.

first: Hideto

last: Furuoka


title: scRNA of GBM tumors

status: Public on Aug 16 2023

city: Lund

first: Mattias

last: Belting

state: Skåne

address: Barngatan

department: Clinical Sciences Lund

country: Sweden

institute: Lund University

summary: Glioblastoma (GBM) presents a formidable clinical challenge due to its complex microenvironment. Here, we introduce tumor-associated foam cells (TAFs), a previously unidentified immune cell entity of lipid droplet (LD)-loaded macrophages, in GBM. Through extensive analyses of patient tumors, together with in vitro and in vivo investigations, we reveal that TAFs exhibit distinct pro-tumorigenic characteristics related to hypoxia, mesenchymal transition, angiogenesis, and impaired phagocytosis. Moreover, TAF presence correlates with worse patient outcome. Our mechanistic investigations demonstrate that TAF formation is facilitated by lipid cargo transfer from extracellular vesicles released by GBM cells. Importantly, we demonstrate that targeting key enzymes involved in LD formation, such as DGAT1 or ACSL, effectively disrupts TAF functionality. This study establishes TAFs as a prominent immune cell entity in GBM and provides valuable insights into their interplay within the microenvironment. Disrupting LD formation to target TAFs presents an interesting avenue for future therapeutic development in GBM.

overall_design: scRNA-Seq

first: Valeria

last: Governa

first: Kelin

middle: G

last: de Oliveira

first: Svenja

last: Offer

first: Myriam

last: Magaña

first: Anna

middle: B

last: Rudenstam

first: Jiaxin

last: Li

first: Sarah

last: Beyer

first: Maria

last: Johansson

first: Ann-Sofie

last: Månsson

first: Charlotte

last: Edvardsson

first: Faris

last: Durmo

first: Axel

last: Boukredine

first: Emelie

last: Gezelius

first: Julien

last: Menard

first: Raquel

last: Garza

first: Johan

last: Jakobsson

first: Therese

last: de Neergaard

first: Pia

last: Sundgren

first: Pontus

last: Nordenfelt

last: Darabi

first: Karin

last: Forsberg-Nilsson

first: Hugo

last: Talbot

last: Bengzon


title: Association analysis of invasive urinary carcinoma in the Shetland sheepdogs and related breeds.

status: Public on Aug 28 2023

city: Bethesda

first: Heidi

last: Parker

address: 50 South Dr. Rm 5347

department: CGB

institute: NHGRI

summary: Naturally occurring canine invasive urinary carcinoma (iUC) closely resembles human muscle invasive bladder cancer in terms of histopathology, metastases, response to therapy and, low survival rate. The heterogeneous nature of the disease has led to the association of large numbers of risk loci in humans, however most are of small effect. There exists a need for new and accurate animal models of invasive bladder cancer. In dogs, distinct breeds show markedly different rates of iUC, thus presenting an opportunity to identify additional risk factors and overcome the locus heterogeneity encountered in human mapping studies. In the association study presented here, inclusive of 100 Shetland sheepdogs and 58 dogs of other breeds, we identify a homozygous protein altering point mutation within the NIPAL1 gene which increases risk by eight-fold (OR=8.42, CI=3.12-22.71), accounting for nearly 30% of iUC risk in the Shetland sheepdog. Inclusion of six additional loci accounts for the majority of disease risk in the breed and explains nearly 75% of the phenotypes in this study. When combined with sequence data from tumors, we show that variation in the MAPK signaling pathway is an overarching cause of iUC susceptibility in dogs.

overall_design: DNA was collected from Shetland sheepdogs, Collies, Border collies, and Australian shepherds with and without diagnosis of invasive urothelial carcinoma (iUC) also known as transitional cell carcinoma of the bladder. SNPs were genotyed using the Illumina CanineHD SNP chip. These data were used in associated studies to find regions of the genome associated with risk or development of iUC.

first: Elaine

last: Ostrander

first: Alexander

last: Harris


title: Systematic identification of RNA-binding proteins and tethered domains that activate exon splicing inclusion [RNA-seq]

first: Brian

last: Yee

overall_design: Differential splicing and expression analysis of RNA-seq data for HEK293T cells and its KD derivatives (shTRNAU1AP, shSTAU2, shSCAF8, shRTCA).

first: Jonathan

last: Schmok

first: Manya

last: Jain

first: Lena

last: Street

first: Maya

last: Gosztyla

first: Evan

last: Boyle

first: Pratibha

last: Jagannatha

first: En-Ching

last: Luo

first: Marko

last: Jovanovic

first: Gene

last: Yeo


title: Clariom D  gene array of HBMEC cells

first: Mattias

last: Belting

summary: Glioblastoma multiforme (GBM) presents a formidable clinical challenge due to its complex microenvironment. Here, we introduce lipid droplet (LD)-loaded macrophages, or tumor-associated foam cells (TAFs), as a previously unidentified immune cell population in GBM. Through extensive analyses of patient tumors, together with in vitro and in vivo investigations, we reveal that TAFs exhibit distinct pro-tumorigenic characteristics related to hypoxia, mesenchymal transition, angiogenesis, and impaired phagocytosis. Moreover, TAF presence correlates with worse patient outcome. Our mechanistic investigations demonstrate that TAF formation is facilitated by lipid cargo from extracellular vesicles released by GBM cells. Importantly, we demonstrate that targeting key enzymes involved in LD formation, such as DGAT1 or ACSL, effectively disrupts TAF functionality. This study establishes TAFs as a prominent immune cell entity in GBM and provides valuable insights into their interplay within the microenvironment. Disruptin

overall_design: 8 samples from 2 Donors, out of which: 2 are HBMECs that received serum-free conditioned media, 2 are HBMECs that received serum-free conditioned media and LDDDs, 2 are HBMECs that received Evs, and 2 are HBMECs that received Evs and LDDDs.

first: Valeria

last: Governa

first: Kelin

last: de Oliveira

first: Svenja

last: Offer

first: Myriam

last: Magaña

first: Anna

last: Rudenstam

first: Jiaxin

last: Li

first: Sarah

last: Beyer

first: Maria

last: Johansson

first: Ann-Sofie

last: Månsson

first: Charlotte

last: Edvardsson

first: Faris

last: Durmo

first: Axel

last: Boukredine

first: Emelie

last: Gezelius

first: Julien

last: Menard

first: Raquel

last: Garza

first: Johan

last: Jakobsson

first: Therese

last: de Neergaard

first: Pia

last: Sundgren

last: Nordenfelt

last: Darabi


title: Clariom D Pico gene array of microdissected GBM areas or PBMCs.

first: Mattias

last: Belting

overall_design: 13 samples, out of which: 4 are from microdissected regions high in macrophage marker intensity (2 with high lipid droplet (LD+) and 2 with low lipid droplet (LD-)); and 9 samples are from patient PBMCs (4 monocytes (HC_t0 and P_t0), 2 macrophages (HC_CTRL), and 2 of macrophages plus extracellular vesicles (HC_EVs)). The LD- and HC_CTRL samples are reference/control samples. The brain samples were microdissected from glioblastoma tissues, underwent RNA extraction with AllPrep DNA/RNA Micro Kit for RNA, and hybridization on Affymetrix Clariom Human D Pico microarray cartrige. The PBMCs samples were isolated by CD14+ microbeads, and underwent RNA extraction with AllPrep DNA/RNA Micro Kit for RNA, and hybridization on Affymetrix Clariom Human D Pico microarray cartrige

first: Valeria

last: Governa

first: Kelin

last: de Oliveira

last: Offer

last: Magaña

first: Pontus

first: Karin

last: Forsberg-Nilsson

first: Hugo

last: Talbot

last: Bengzon


title: Characterization of transcriptional profiles associated with stress-induced neuronal activation in Arc-TRAP mice

status: Public on Aug 14 2023

city: Mainz

first: Susanne

last: Gerber

address: Staudinger Weg 9

department: Institute for Human Genetics

institute: University Medicine Mainz

summary: Chronic stress has become a predominant factor associated with a variety of psychiatric disorders, such as depression and anxiety, in both humans and animal models. Although multiple studies have looked at transcriptome after social defeat stress, these studies focus on bulk tissues, which could dilute important molecular signatures of social interaction activated cells.In this study, we employed the Arc-TRAP mouse model in conjunction with chronic social defeat (CSD) to selectively isolate activated nuclei (AN) populations in the ventral hippocampus (vHIP) and prefrontal cortex (PFC) brain regions of resilient and susceptible animals. We subsequently performed nuclear RNA-seq to reveal the transcriptional signatures underlying susceptible and resilient behaviors and conducted a detailed analysis on these specific populations.Our findings provide a novel view of stress-exposed neuronal activation and the molecular response mechanisms, which may have important implications for understanding the development of stress-related disorders.

overall_design: Nuclear RNA-seq of activated nuclei (GFP+) and non-activated nuclei (GFP-) from Prefrontral cortex (PFC) and ventral hippocampus (vHIP) of resilience, susceptible (and control) animals  following chronic social defeat.

first: Tamer

last: Butto

first: Monika

last: Chongtham

first: Kanak

last: Mungikar

first: Dewi

last: Hartwich

first: Matthias

last: Linke

first: Nicolas

last: Ruffini

first: Konstantin

last: Radyushkin

first: Susann

last: Schweiger

first: Jennifer

last: Winter


title: The establishment of a CTCF activity reporter for systematic stratification of CTCF binding sites

status: Public on Aug 12 2023

city: Oxford

first: Felice

middle: Hoching

last: Tsang

state: Oxfordshire

address: John Radcliffe Hospital/Headley Way

department: Weatherall Institute of Molecular Medicine

institute: University of Oxford

summary: While the elements encoding enhancers and promoters have been relatively well studied, the full spectrum of insulator elements which bind the CCCTC binding factor (CTCF), is relatively poorly characterised. In part, this is due the fact that their roles and activity is greatly influenced by their genomic context. Here we have developed an experimental system to determine the ability of consistently sized, individual CTCF elements to interpose between enhancers and promoters and thereby reduce gene expression during differentiation. Importantly each element is tested in the identical location thereby minimising the effect of genomic context. We found no correlation between the ability of CTCF elements to block enhancer-promoter activity with the amount of CTCF or cohesin bound at the natural genomic sites of these elements; the degree of evolutionary conservation; or their resemblance to the consensus core sequences. Nevertheless, we have shown that the strongest enhancer-promoter blockers include a previously described bound element lying upstream of the CTCF core motif. In addition, we found other uncharacterised DNAse1 footprints located close to the core sequence that may affect function. We have developed a high throughput assay of CTCF elements which will enable researchers to sub-classify CTCF elements in an unbiased way.

overall_design: Artificial CTCF binding sequences were genetically engineered in mouse ESCs. These mESCs were subjected to an in vitro erythroid differentiation protocol (doi: 10.1371/journal.pone.0261950) and purified CD71+ erythroid cells derived from differentiated Wildtype (WT) or mutant mouse Embryonic Stem (mES) cells were analysed by CTCF ChIP-seq.

middle: H

first: Rosa

last: Stolper


title: Transcriptomic analysis of Paenarthrobacter nicotinovorans ATCC 49919 nicotine metabolism

status: Public on Aug 07 2023

city: Iași

first: Marius

last: Mihasan

state: Iași

address: Bulevardul Carol I, nr. 20 A

department: Biology

country: Romania

institute: Alexandru Ioan Cuza University of Iasi

summary: Paenarthrobacter nicotinovorans pAO1 is a nicotine degrading microorganism that shows promising applications in converting nicotine-containing waste into useful green chemicals. Its biotechnological applications are nevertheless hampered by the lack of knowledge and tools to perform genetic and metabolic engineering. The objective of the work is to provide the first transcriptome of the strain and is a second step in our envisioned complete omics characterization of nicotine metabolism in P. nicotinovorans ATCC 49919. Acknowledgements. This work was supported by a grant of the Romanian Ministry of Education and Research, CNCS - UEFISCDI, project number PN-III-P4-ID-PCE-2020-0656, within PNCDI III.

overall_design: The strain was grown on citrate medium with and without nicotine. Cells were harvested at three different timepoints correlated with cellular growth and nicotine catabolism. The first timepoint (T1) was set at ~5 hours after inoculation (and nicotine-supplementation), representing the start of the exponential phase (and of nicotine catabolism). The second timepoint (T2), at ~10 HAI, captures the transition from the exponential to stationary phase: the on-going degradation of nicotine and its depletion from the growth medium. The third timepoint (T3), at 24 HAI, represents the stationary phase, when nicotine has been depleted from the growth medium. Total RNA was isolated, poly-adenylated, and directly sequenced using the Oxford Nanopore Technology (ONT) MinION Mk1B device coupled to a Flongle adapter. Basecalling was performed using Guppy_6.3.2 and high accuracy. Basecalled data was analysed using the nf-core/nanoseq pipeline for quality assessment, mapping to the reference genome, transcriptome assembly, transcript quantification and differential gene expression.

first: Amada

last: El-Sabeh


title: PML modulates epigenetic composition of chromatin to regulate expression of pro-metastatic genes in triple-negative breast cancer [RNA-seq]

last: Bernardi

overall_design: RNA-sequencing (RNA-seq) in control and PML silenced MDA-MB-231 cells.

first: Cristina

last: Fracassi

first: Martina

last: Ugge’

first: Mohamed

last: Abdelhalim

first: Ettore

last: Zapparoli

first: Dejan

last: Lazarevic

first: J

last: Morelli

first: Philippe

last: Collas


title: Torsion of the heart tube by shortage of progenitor cells: identification of Greb1l as a genetic determinant of criss-cross hearts in mice

status: Public on Aug 09 2023

city: Paris

first: Sigolène

last: Meilhac

address: 24 boulevard du Montparnasse

country: France

institute: Institut Imagine, Institut Pasteur

summary: Despite their burden and impact, most congenital defects remain poorly understood by lack of knowledge of the embryological mechanisms. Here, we identify Greb1l mutants as the first mouse model of criss-cross heart. Based on 3D quantifications of shape changes, we demonstrate that torsion of the atrioventricular canal occurs together with supero-inferior ventricles at E10.5, after heart looping. Mutants phenocopy specific features of partial deficiency in retinoic acid signalling, suggesting that GREB1L is a novel modulator of this signalling. Spatio-temporal gene mapping and cross-correlated transcriptomic analyses further reveal the role of Greb1l in maintaining a pool of precursor cells during heart tube elongation, by controlling ribosome biogenesis and cell differentiation. Growth arrest and malposition of the outflow tract are predictive of abnormal tube remodelling in mutants. Our work on a rare cardiac malformation opens novel perspectives on the origin of a broader spectrum of congenital defects associated with GREB1L in humans.

overall_design: Transcriptomic analysis of the microdissected cardiac region at E8.5 of two Greb1l mutant mouse lines (G3 and G17), 4 mutants and 4 control littermates each.

first: Ségolène

last: Bernheim

first: Adrien

last: Borgel

last: Cagnard

first: M

last: Zarrate

first: Christine

last: Bole


title: Multiomic Single Cell Sequencing Identifies Stemlike Nature of Mixed Phenotype Acute Leukemia and Provides Novel Risk Stratification [DAb-seq]

city: San Francisco

first: Catherine

last: Smith

state: California

address: 513 Parnassus Avenue

department: Medicine

institute: University of California, San Francisco

summary: Mixed phenotype acute leukemia (MPAL) also known as acute leukemia of ambiguous lineage (ALAL), is characterized by leukemic blasts with both lymphoid and myeloid cell surface markers.   Here, we use SC multiomic profiling on newly diagnosed MPAL samples to characterize the immunophenotypic, genetic, and transcriptional landscapes of MPAL. This profiling allows us to definitively contradict the paradigm of MPAL as a disease on a continuum with myeloid and lymphoid lineage acute leukemias, and instead identifies MPAL as a distinct, stem-like disease that, unlike other leukemias, cannot be defined by genetics alone. We further describe a stem cell gene expression signature for MPAL that can predict patient survival. These results broaden our understanding of MPAL biology and suggest a path toward novel risk stratification for MPAL. Importantly, these findings have potential to direct treatment and, hopefully, ultimately improve the prognosis of this disease.

overall_design: Samples from 14 adult patients with de novo MPAL were analyzed for single cell DNA, RNA, protein.

first: Cheryl

middle: A

last: Peretz

first: Vanessa

last: Kennedy

first: Anushka

last: Walia

first: Cyrille

last: Delley

first: Andrew

last: Koh

first: Elaine

last: Tran

first: Iain

last: Clark

first: Corey

last: Hayford

first: Chris

last: Amato

first: Kristina

last: Fontanez

first: Ritu

last: Roy

first: Aaron

last: Logan

first: Alexander

last: Perl

first: Adam

last: Abate

last: Olshen


title: Immune metabolic interplay drives the protective antibody response pre-vaccination with Dengue virus Vaccine

status: Public on Jul 27 2023

city: Blainville

first: Adam-Nicolas

last: Pelletier

state: Quebec

address: 97, Montcalm

country: Canada

institute: RPM Bioinfo Solutions

summary: Protective immunity to dengue virus (DENV) requires antibody response to all four serotypes. Systems vaccinology identified pre-vaccination mechanisms predictive of broad antibody responses after immunization with a tetravalent live-attenuated DENV vaccine candidate (Butantan-DV/TV003). Anti-inflammatory pathways including TGF-b signaling expressed by CD68low monocytes and the metabolokines phosphatidylcholine (PC) and phosphatidylethanolamine (PE) were positively correlated with broadly neutralizing Ab responses against DENV. In contrast expression of pro-inflammatory pathways and cytokines (IFN, IL-1) in CD68hi monocytes and primary and secondary bile acids negatively correlated with broad DENVDENV specific Ab responses. Induction of TGF-b and IFNs respectively by PC/PE and bile acids in CD68low and CD68hi monocytes and their impact on viral sensing was confirmed in vitro. We show that the balance between metabolites and pro- or anti-inflammatory innate immune cells drives broad and protective B cell response to the live-attenuated dengue vaccine.

overall_design: Prevaccination PBMC samples compared between high and low breadth of the neutralizing Ab response to Dengue vaccine Butantan-TV003

first: Gabriela

middle: P

last: Sanchez

first: Abdullah

last: Izmirly

first: Mark

last: Watson

first: Tiziana

last: Di Pucchio

first: Karina

middle: I

last: Carvalho

first: Abdelali

last: Filali-Mouhim

first: Eustache

last: Paramithiotis

first: Maria

last: Timenetsky

last: Precioso

first: Jorge

last: Kalil

first: Michael

last: Diamond

first: Elias

last: Haddad

first: Esper

last: Kallas

first: Rafick

last: Sekaly


title: HD2B and HD2C interact with Argonaute 4 to promote tolerance and heterochromatin stabilization during heat stress

first: Xiangsong

last: Chen

address: Bayi Road

institute: Wuhan university

type: Methylation profiling by high throughput sequencing

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

overall_design: Refer to individual Series


title: Premature aging and reduced cancer incidence associated with near-complete body-wide Myc inactivation

status: Public on Aug 03 2023

city: pittsburgh

first: Huabo

last: Wang

state: PA

address: 4401 Penn Avenue

institute: Children hospital of pittsburgh

summary: Deregulation of the MYC proto-oncogene alters metabolic, translational, cell cycle and other functions in ways that are conducive to tumor induction and maintenance. Myc+/- mice are healthier and age slower than control mice but the long-term ramifications of more complete Myc loss remain unknown. We now describe the life-long consequences of body-wide Myc inactivation initiated post-natally. “MycKO” mice rapidly acquire numerous features of premature aging including altered body composition and habitus, metabolic dysfunction, hepatic steatosis and the dysregulation of numerous gene sets involved in functions that normally deteriorate with aging. Yet, MycKO mice have an extended life span that correlates with a 4-5-fold lower lifetime cancer incidence. Aging tissues from normal mice and humans deregulate many of the same gene sets as do young MycKO mice while also down-regulating Myc and many of its target genes. Aging and its associated cancer predisposition are thus highly coupled via Myc and can be genetically separated.

overall_design: Comparative gene expression profiling analysis of RNA-seq data for MycKO and WT in 5 month and 20 month old mice's omental adipose tissue, liver and skeletal muscle .

first: Edward

middle: V

last: Prochownik


title: Multiomic Single Cell Sequencing Identifies Stemlike Nature of Mixed Phenotype Acute Leukemia and Provides Novel Risk Stratification

first: Catherine

last: Smith


title: Teosinte Pollen Drive guides maize domestication and evolution by RNA interference [RNA-seq]]

status: Public on Jul 26 2023

city: Cold Spring Harbor

first: Robert

last: Martienssen

state: NY

address: 1 Bungtown Rd

department: Delbruck Bldg.

institute: Cold Spring Harbor Laboratory

summary: Meiotic drivers subvert Mendelian expectations by manipulating reproductive development to bias their own transmission. Chromosomal drive typically functions in asymmetric female meiosis, while gene drive is normally postmeiotic and typically found in males.  Cryptic drive is thought to be pervasive and can be unleashed following hybridization with a naïve genome, resulting in sterility and hybrid incompatibility. Using single molecule and single pollen genome sequencing, we describe an instance of gene drive in hybrids between maize (Zea mays ssp. mays) and teosinte mexicana (Zea mays ssp. mexicana), that depends on RNA interference (RNAi) in the male germline. Multiple hairpin-derived small RNA from mexicana target a novel domestication gene,  Teosinte Drive Responder,  that is required for pollen fertility and has undergone selection for immunity to RNAi.  Introgression of mexicana into early cultivated maize is thought to have been critical to its geographical dispersal throughout the Americas.  A survey of maize landraces and sympatric populations of teosinte mexicana reveals allelic bias at genes required for RNAi on at least 4 chromosomes that are also subject to gene drive in pollen from synthetic hybrids.  Teosinte Pollen Drive likely played a major role in maize domestication, and offers an explanation for the widespread abundance of hairpin-encoded and other endogenous small RNA  in the germlines of plants and animals.

sample_organism: Zea mays subsp. mays x Zea mays subsp. mexicana

overall_design: Total RNA sequencing (rRNA depleted) of tpd1;tpd2, Tpd1+/-;Tpd2+/-, and Tpd1+/-;tpd2 bulk pollen

first: Benjamin

last: Berube

first: Evan

last: Ernst

last: Roche

first: Jonathan

last: Cahn

first: Cristiane

last: Alves

first: Jason

last: Lynn

first: Jeffrey

last: Ross-Ibarra

first: Jerry

last: Kermicle


title: Merlin rescue drives Wnt signalling

first: Charlotte

last: Eaton

institute: UCSF

summary: To investigate the effect of Merlin rescue on cell proliferation in 3D, we grew subcutaneous xenografts from NF2-deficient CH-157MN meningioma cells harboring doxycycline inducible WT-Merlin. Mice were treated with or without doxycycline and Merlin induction was confirmed 24 hours after induction with Western blot. We performed single-cell RNA sequencing on five Merlin-deficient tumors and seven Merlin rescue tumors

overall_design: 3 million CH157-MN meningioma cells hosting doxycycline inducible WT Merlin were injected into the right flank of 4-6wk old NU/NU mice. Doxycycline (20ug/ml) was supplemented in the water of the treatment group at the time of injection. Tumours were dissociated using Collagenase type 7 and 0.25% trypsin. Single cells were processed through a 10X Genomics Chromium Controller and libraries were created using the Chromium Single Cell 3’ Library & Gel Bead Kit v3. Libraries were sequenced on a NovaSeq S4 6000.

first: David

last: Raleigh


title: Canabidiol (CBD) modulates the effect of ethanol on the fibroblast cells transcriptome in vitro

status: Public on Aug 01 2023

city: Kraków

first: Artur

last: Gurgul

address: Rędzina 1C

department: Center for Experimental and Innovative Medicine

country: Poland

institute: University of Agriculture in Krakow

summary: Considering reports about positive role of Cannabidiol (CBD) in alcohol abuse disorders, in this study we used cellular model of human fibroblasts to analyse the effect of CBD on ethanol-treated cells. We assumed, that CBD will (to some extent), prevent adverse transcriptional changes driven by alcohol administration and this effect will be detectable on the transcriptome level. As a by-product of this analysis, ethanol and CBD alone stimulated transcriptome changes were also described. We moreover considered that CBD effects are dose and time-dependent. As a model for these analyses we selected human fibroblast cell line as a most abundant cell type in human body that express e.g. both cannabinoid receptors (CB1 and CB2) and is able to metabolize ethanol trough alcohol dehydrogenase activity.

overall_design: In this study the transcriptome of human fibroblasts was analysed in response to Cannabidiol (CBD), Ethanol (EtOH) and CBD/EtOH mixture treatment. CBD and EtOH were applied in various concentrations (CBD -  0.75 and 3 uM; EtOH - 0.25 and 0.75% in a culture medium). Each treatment was analysed at two tomepoints, namely 6 and 12 hours of incubation. Each treatment was prepared in triplicates, however sequencing results were not obtained for all samples. Control (CTR), untreated cells were also included in the analysis.

first: Jakub

last: Żurowski

first: Tomasz

last: Szmatoła

first: Sebastian

last: Sawicki

first: Mirosław

last: Kucharski

first: Ewa

last: Ocłoń


title: Teosinte Pollen Drive guides maize domestication and evolution by RNA interference [small RNA-seq]

last: Martienssen

platform_organism: Zea mays subsp. mays x Zea mays subsp. mexicana

overall_design: Small RNA sequencing of Tpd1/tpd1;Tpd2/tpd2 and tpd1;tpd2 pollen and leaf, and dcl2T-/- and dcl2-mu1-/- pollen


title: The protein U5-52K is required for T cell homeostasis by maintaining splicing efficiency

status: Public on Jul 31 2023

city: Berlin

first: Miriam

last: Bertazzon

address: Thielallee 63

institute: Freie Universität Berlin

summary: U5-52K is a nuclear protein present in the U5 snRNP spliceosome subunits and it is essential for the mouse embryo development. In fact its absence blocks embryo at the developmental stage at E 10.5 with subsequence reasbsorbtion. Therefore, we used a CD4-Cre-knockout strategy to abrogate U5-52K in T cells, allowing us to delineate the consequences of splicing machinery interferences with T cell homeostasis. Several Differentially Spliced Variants and Differentially Expressed Genes were detected in T cells lacking U5-52K indicating its involvement in gene transcription regulation.

overall_design: The RNA extracted from CD4+ isolated T cells from spleen and lymph nodes from three cKO mice (U5-52Kf/f CD4-Cretg) and three control mice (Control: U5-52Kwt/f CD4-Cretg and U5-52Kf/f CD4-Cre-) were sequenced using RNA-seq technology.

first: Almudena

last: Hurtado-Pico

first: Carlos

last: Plaza-Sirvent

first: Marco

last: Preußner

first: Florian

last: Heyd

first: Christian

last: Freund


title: Multiomic Single Cell Sequencing Identifies Stemlike Nature of Mixed Phenotype Acute Leukemia and Provides Novel Risk Stratification [PIP-seq]

first: Catherine

last: Smith

first: Cheryl

last: Peretz

first: Vanessa

last: Kennedy

first: Anushka

last: Walia

first: Cyrille

last: Delley

first: Andrew

last: Koh

first: Elaine

last: Tran

first: Iain

last: Clark

first: Corey

last: Hayford

first: Chris

last: Amato

first: Kristina

last: Fontanez

first: Ritu

last: Roy

first: Aaron

last: Logan

first: Alexander

last: Perl

first: Adam

last: Abate

last: Olshen


title: Teosinte Pollen Drive guides maize domestication and evolution by RNA interference [iPARE-seq]

first: Robert

last: Martienssen

overall_design: iPARE sequencing of Tpd (Tpd1+/-;Tpd2+/) and WT (tpd1;tpd2) bulk pollen

first: Benjamin

last: Berube

first: Evan

last: Ernst

last: Roche

first: Jonathan

last: Cahn

first: Cristiane

last: Alves

first: Jason

last: Lynn

first: Jeffrey

last: Ross-Ibarra

first: Jerry

last: Kermicle


title: Teosinte Pollen Drive guides maize domestication and evolution by RNA interference [dna_single_pollen]

overall_design: Single-pollen grain sequencing of Tpd1+/-;Tpd2+/- plants.


title: NOTCH-YAP1/TEAD-DNMT1 axis drives hepatocyte reprogramming into intrahepatic cholangiocarcinoma [bulk RNA-Seq]

status: Public on Jul 25 2023

city: Pittsburgh

first: Shuchang

last: Liu

address: 203 Lothrop Street

institute: University of Pittsburgh

summary: BACKGROUND AND AIM: Intrahepatic cholangiocarcinoma (ICC) is a liver tumor of increasing incidence and devastating prognosis. A critical barrier to developing an effective regimen for ICC is its intra- and inter-tumoral molecular heterogeneity, which may in part be due to its diverse cellular origin. We investigated clinical relevance and the molecular mechanisms underlying hepatocyte (HC)-driven ICC development.   METHODS: Expression of ICC driver genes in human diseased livers at risk for ICC development were examined. Sleeping beauty and hydrodynamic tail vein injection based Akt-NICD/YAP1 ICC model was used to investigate pathogenetic roles of SOX9 and YAP1 in HC-driven ICC. These models and in silico studies led to identification of DNA methyltransferase-1 (DNMT1) as a YAP1 target, which was validated by both loss- and gain-of-function studies.   RESULTS: Co-expression of AKT along with NICD/YAP1 in HC yielded ICC which resembled proliferative, Notch-activated, and stem cell-like subclasses of clinical ICC. NICD induced SOX9 and YAP1 in HC-driven ICC and deletion of either significantly delays ICC development. Yap1 deletion or TEAD inhibition, but not Sox9 deletion, impaired HC-to-biliary epithelial cell (BEC) reprogramming. DNMT1 was discovered as a novel downstream effector of YAP1-TEAD complex that directs HC-to-BEC/ICC fate-switch. DNMT1 loss prevented Notch/YAP1-dependent HC-driven cholangiocarcinogenesis, and DNMT1 re-expression restored ICC development following TEAD repression. Co-expression of DNMT1 with AKT was sufficient to induce tumor development including ICC. DNMT1 was detected in subset of HCs and dysplastic BECs in cholestatic human livers prone to ICC development.   CONCLUSION: We identify a novel NOTCH-YAP1/TEAD-DNMT1 axis essential for of HC-to-BEC/ICC conversion, may be relevant in cholestasis-to-ICC pathogenesis in the clinic.

overall_design: mRNA profiles of two conditions: WT healthy control liver (3 repeats) and human AKT+NICD ICC liver (5 repeats)

first: Shikai

last: Hu

first: Laura

last: Molina

first: Junyan

last: Tao

first: Silvia

first: Mohammed

last: Hassan

first: Sucha

last: Singh

first: Minakshi

last: Poddar

last: Bell

first: Daniela

last: Sia

first: Michael

last: Oertel

first: Reben

last: Raeman

first: Kari

last: Nejak-Bowen

first: Aatur

last: Singhi

first: Jianhua

last: Luo

first: Satdarshan

last: Monga

first: Sungjin

last: Ko


title: NOTCH-YAP1/TEAD-DNMT1 axis drives hepatocyte reprogramming into intrahepatic cholangiocarcinoma


title: NOTCH-YAP1/TEAD-DNMT1 axis drives hepatocyte reprogramming into intrahepatic cholangiocarcinoma [ChIP-Seq]

overall_design: ChIP-seq profile with DNMT1 retreatment and the corresponding DNA input

first: Aaron


title: Exploring the Impact of Cyclodipeptide on Fungal Metabolism: Insights into Membrane and Metabolic Responses

status: Public on Jul 23 2023

city: MALAGA

first: DAVID

last: VELA-CORCIA

address: CAMPUS DE TEATINOS

department: MICROBIOLOGIA

institute: UNIVERSIDAD DE MALAGA

sample_organism:
Caenorhabditis elegans
Botrytis cinerea

platform_organism:
Caenorhabditis elegans
Botrytis cinerea


title: IL-1b-mediated transcriptional changes during early, middle, and late differentiation of human adipose-derived stem cells

city: Stockholm

first: Kaisa

last: Hofwimmer

address: Blickagången 16

institute: Karolinska Institutet

summary: To map transcriptional changes in response to IL-1b treatment during adipogenesis, human adipose-derived stem cells were differentiated in the presence or absence of IL-1b, and RNA-seq was performed on cells collected during early, middle, and late differentiation stages.

overall_design: Human adipose-derived stem cells originating from the subcutaneous white adipose tissue of a male donor (16 years old, BMI 24) were treated continuously with human recombinant IL-1b (10 ng/ml) or vehicle (water, 1:1000) from start of adipogenic induction, and collected at three different time points (day 2, 5, and 9 of differentiation). Data is from 4 independent experiments (1 replicate per experiment).

first: Jurga

last: Laurencikiene


title: Teosinte Pollen Drive guides maize domestication and evolution by RNA interference

first: Robert

last: Martienssen


title: The YAP-TEAD complex promotes senescent cell survival by lowering endoplasmic reticulum stress [scRNA-seq]

status: Public on Jul 13 2023

city: Baltimore

first: Supriyo

last: De

state: Maryland

address: 251 Bayview Blvd

department: Laboratory of Genetics and Genomics

institute: NIA-IRP, NIH

summary: Sublethal cell damage can trigger a complex adaptive program known as senescence, characterized by growth arrest, resistance to apoptosis, and a senescence-associated secretory phenotype (SASP).  As senescent cells accumulating in aging organs are linked to many age-associated diseases, senotherapeutic strategies are actively sought to eliminate them.  Here, a whole-genome CRISPR knockout screen revealed that proteins in the YAP-TEAD pathway influenced senescent cell viability.  Accordingly, treating senescent cells with a drug that inhibited this pathway, Verteporfin (VPF), selectively triggered apoptotic cell death and derepressed DDIT4, in turn inhibiting mTOR.  Reducing mTOR function in senescent cells diminished endoplasmic reticulum (ER) biogenesis, causing ER stress and apoptosis due to high demands on ER function by the SASP.  Importantly, VPF treatment decreased senescent cell numbers in the organs of old mice and mice exhibiting doxorubicin-induced senescence.  We present a novel senolytic strategy that eliminates senescent cells by hindering ER activity required for SASP production.

overall_design: Etoposide-induced senescent (ETIS) cells were either untreated or treated with verteporfin (VPF, 1.5 mM) for 72 hours. Cells were trypsinized, washed and then subjected to scRNA-seq experiment.

first: Carlos

last: Anerillas

first: Krystyna

last: Mazan-Mamczarz

first: Allison

last: Herman

first: Rachel

last: Munk

first: Kwan-Wood

last: Lam

first: Miguel

last: Calvo-Rubio

first: Amanda

last: Garrido

first: Dimitrios

last: Tsitsipatis

first: Jennifer

last: Martindale

first: Gisela

last: Altés

first: Martina

last: Rossi

first: Yulan

last: Piao

first: Jinshui

last: Fan

first: Chang-Yi

last: Cui

first: Kotb

last: Abdelmohsen

first: Rafael

last: de Cabo

first: Myriam

last: Gorospe


title: Exploring the Impact of Cyclodipeptide on Fungal Metabolism: Insights into Membrane and Metabolic Responses [C. elegans]

first: DAVID

last: VELA-CORCIA

summary: This study investigates the effects of cyclodipeptide on fungal and nematode metabolism, specifically focusing on its impact on membrane composition and metabolic responses. Metabolomic profiles of treated and untreated fungal cultures were compared to unravel the molecular changes induced by cyclodipeptide, with a particular emphasis on membrane phospholipids such as monoolein and phosphatidyl ethanolamine, as well as other plasma membrane components like ergosterol and its derivative products. The results reveal significant alterations in the metabolites present in the presence of cyclodipeptide. Specifically, the levels of cyclo (Pro-Tyr) monoolein were found to decrease, while phosphatidyl ethanolamine levels increased. Moreover, the levels of ergosterol and its derivatives were observed to decrease as well. These findings indicate that cyclodipeptide has a profound impact on the metabolic pathways of the fungal system under investigation. The study suggests that cyclodipeptide not only influences membrane phospholipids but may also have broader effects on membrane proteins, cellular signaling, and communication. Furthermore, the observed changes in metabolomic profiles hint at potential alterations in cellular processes beyond membrane composition, possibly involving gene expression and enzyme activity. Understanding the mechanisms behind these effects holds considerable scientific interest and practical implications. The ability of cyclodipeptide to selectively target membrane components presents opportunities for studying and manipulating membrane function in various organisms. Additionally, the discovery of new bioactive natural products like cyclodipeptide opens avenues for developing innovative therapeutics or agricultural agents. Further research is needed to fully comprehend the intricate mechanisms underlying the observed effects of cyclodipeptide on fungal metabolism.

overall_design: The worms were synchronized using a bleaching solution (0.5 M NaOH and 1.2% NaClO). Then, the obtained embryos or L1 stage larvae were exposed to 0.25 mg mL-1 Cyclo (Pro-Tyr) solution for 24 hours at 20ºC, and the effects of the chemical on survival rate, lifespan, and gene expression were measured.


title: Spectrum of Response to Platinum and PARP Inhibitors in Germline BRCA Associated Pancreatic Cancer in the Clinical and Pre-clinical Setting

city: Ramat Gan

first: Talia

last: Golan

state: <None>

address: Tel Hashomer

department: Oncology Institute

country: Israel

institute: Sheba Medical Center

summary: Germline BRCA-associated pancreatic ductal adenocarcinoma(glBRCA-PDAC) tumors aresusceptible to platinum/PARP-inhibition. The clinical outcomesof 125 glBRCA-PDAC patients was stratified based on the spectrum of response to platinum/PARP-inhibition: i)Refractory(OS<6 months) ii)Durable response followed by acquired-resistance(OS<36 months); iii)Long-term responders(OS>36 months).  Patient-derived-xenografts(PDX) were generated from 25 glBRCA-PDAC patients at different clinical time-points. Response to platinum/PARP-inhibition in-vivo and ex-vivo culture(EVOC) correlated with clinical response. We deciphered the mechanisms of resistance in glBRCA-PDAC and identified homologous recombination(HR)-proficiency and secondary-mutations restoring partial functionality as the most dominant resistant mechanism. Yet, a subset of HR-deficient(HRD) patients demonstrated clinical resistance. Their tumors displayed basal-like molecular subtype and were more aneuploid. Tumor-mutational-burden(TMB) was high in HRD-PDAC and significantly higher in tumors with secondary mutations. Anti-PD1 attenuated tumor growth in a novel humanized glBRCA-PDAC PDX-model. This work demonstrates the utility ofpreclinicalmodels, including EVOC, to predict response of glBRCA-PDAC to treatment, whichhas potential to inform time-sensitive medical decisions.

overall_design: To investigate thee expression patterns of our BRCA PDAC PDX models we sequenced PDX models  with 1-3 biological replicates (i.e. different xenograft generaition in mice).

first: Chani

last: Stossel

first: Maria

last: Raitses-Gurevich

first: Rotem

last: Tal

first: Itay

last: Tirosh


title: The YAP-TEAD complex promotes senescent cell survival by lowering endoplasmic reticulum stress

first: Supriyo

last: De


title: NOTCH-YAP1/TEAD-DNMT1 axis drives hepatocyte reprogramming into intrahepatic cholangiocarcinoma [RNA-Seq]

first: Shuchang

last: Liu

summary: We reported the transcritpome in the healthy control liver of wild-type mice, liver bearing myrAKT-NICD driven ICC and livers bearing myrAKT-YAP driven Sox9 deleted HCC from liver-specific Sox9 knockout mice

overall_design: Liver samples were taken at 5 weeks post hydrodynamic tailvein injection of myrAKT-NICD or myrAKT-YAP expression plasmid

first: Shikai

last: Hu

first: Laura

last: Molina

first: Junyan

last: Tao

first: Silvia

first: Mohammed

last: Hassan

first: Sucha

last: Singh

first: Minakshi

last: Poddar

first: Aaron

last: Bell

first: Daniela

last: Sia

first: Michael

last: Oertel

first: Reben

last: Raeman

first: Kari

last: Nejak-Bowen

first: Aatur

last: Singhi

first: Jianhua

last: Luo

first: Satdarshan

last: Monga

first: Sungjin

last: Ko


title: Exploring the Impact of Cyclodipeptide on Fungal Metabolism: Insights into Membrane and Metabolic Responses [B. cinerea]

first: DAVID

last: VELA-CORCIA

overall_design: RNA from B. cinerea B05.10 was extracted from clumps after 24 h growth on PDB supplemented with 0.25 mg mL-1 of Cyclo (Pro-Tyr), and DMSO as control, at 28ºC 150rpm, using NucleoSpin RNA Plant and Fungi kit (Macherey-Nagel), according to the manufacturer’s instructions.


title: The YAP-TEAD complex promotes senescent cell survival by lowering endoplasmic reticulum stress [scRNA-seq_mouse]

first: Supriyo

last: De

overall_design: ≈24 month old mice were treated with a round of either DMSO (5 consecutive days), Verteporfin (50 mg/kg, 5 consecutive days), or ABT-737 (25 mg/kg, 3 consecutive days), and sacrificed a week after the last treatment.

first: Carlos

last: Anerillas

first: Krystyna

last: Mazan-Mamczarz

first: Allison

last: Herman

first: Rachel

last: Munk

first: Kwan-Wood

last: Lam

first: Miguel

last: Calvo-Rubio

first: Amanda

last: Garrido

first: Dimitrios

last: Tsitsipatis

first: Jennifer

last: Martindale

first: Gisela

last: Altés

first: Martina

last: Rossi

first: Yulan

last: Piao

first: Jinshui

last: Fan

first: Chang-Yi

last: Cui

first: Kotb

last: Abdelmohsen

first: Rafael

last: de Cabo

first: Myriam

last: Gorospe


title: Teosinte Pollen Drive guides maize domestication and evolution by RNA interference [WGS]

first: Robert

last: Martienssen

overall_design: WGS of separately maintained Tpd1;Tpd2 lineages (BC8S3, BC5S2) and bulk segregation analysis (BSA) maternal pools

first: Benjamin

last: Berube

first: Evan

last: Ernst

last: Roche

first: Jonathan

last: Cahn

first: Cristiane

last: Alves

first: Jason

last: Lynn

first: Jeffrey

last: Ross-Ibarra

first: Jerry

last: Kermicle


title: Gene expression data of murine hematopoietic stem cells after anemic stress

status: Public on Jun 30 2023

city: Kumamoto

first: Kenichi

last: Miharada

address: 2-2-1 Honjo, Chuo-ku

institute: Kumamoto University

summary: Adult hematopoietic stem cells (HSCs) react to various stress conditions by rapidly proliferating and preferentially differentiating towards desired cell types. However, it is unclear whether and how HSCs respond to severe anemic conditions. Here we demonstrate that HSCs rapidly proliferate and enhance their erythroid potential upon induction of acute anemia. Under severe anemic conditions, the concentration of erythropoietin (EPO) does not increase in the bone marrow. Instead, lipoprotein profiles largely changed, and the concentration of apolipoprotein E (ApoE) increased. In HSCs, transcription levels of lipid metabolism-related genes such as very low-density lipoprotein receptor (Vldlr) were significantly up-regulated. Stimulation of HSCs with recombinant ApoE enhanced the erythroid potential, while HSCs of ApoE knockout mice did not respond to the hemolysis induction. We also found that VLDLRhighHSCs have higher erythroid differentiation potential, particularly after acute anemia induction. VLDLRhighHSCs were epigenetically distinct from VLDLRlowHSCs, as their chromatin accessibility was lower and more chromatin regions were closed upon acute anemia induction. Finally, we identified that the chromatin regions closed upon the acute anemia induction were mainly binding sites of a transcription factor Erg. Treatment of HSC with Erg inhibitor enhanced erythroid differentiation potential, as seen in the ApoE treatment. Our findings indicate that lipoprotein metabolism, particularly ApoE, plays a crucial role in HSC regulation under severe anemia conditions in a non-canonical fashion, unlike a conventional factor such as EPO.

overall_design: Ten weeks old C57BL/6JRj mice were injected with PBS or 60 mg/kg of phenylhydrazine, or phlebotomized, and 3 days later CD150+ CD48- c-Kit+ Sca-I+ Lineage- cells were sorted from the bone marrow of those mice.

first: Mark

last: van der Garde


title: The YAP-TEAD complex promotes senescent cell survival by lowering endoplasmic reticulum stress [bulk RNA-seq]

first: Supriyo

last: De

overall_design: RNA-sequencing analysis of WI-38 human diploid fibroblasts with three independent replicates per group:  Etoposide-induced senescent (ETIS) cells were obtained by treatment with 50 μM etoposide for 6 days, and treated with verteporfin (VPF, 1.5 μM) or vehicle (0.3% DMSO) for 48 hours, while proliferating cells treated with vehicle were included as controls.

first: Carlos

last: Anerillas

first: Krystyna

last: Mazan-Mamczarz

first: Allison

last: Herman

first: Rachel

last: Munk

first: Kwan-Wood

last: Lam

first: Miguel

last: Calvo-Rubio

first: Amanda

last: Garrido

first: Dimitrios

last: Tsitsipatis

first: Jennifer

last: Martindale

first: Gisela

last: Altés

first: Martina

last: Rossi

last: Piao


title: Mycobacterium tuberculosis Rv0102-regulated copper uptake facilitates bacterial escape from phagolysosome

city: Chongqing

first: Hongxiang

last: Xu

address: Tiansheng Road

institute: Southwest University

summary: The host restricts Mycobacterium tuberculosis (Mtb) access of transition metal ions to inhibit its growth. Cu is essential for the survival of Mtb, but Cu excess is toxic. During co-evolution, Mtb has developed various mechanisms to maintain copper homeostasis. In this report, we firstly found Mtb Rv0102 encoded membrane protein is critical for Mycobacterium Cu uptake. The intracellular Cu level of M. smegmatis (Ms) Rv0102 homolog MSMEG_4702 knockout strain decreased threefold than the wild type, the deletion mutant was more tolerant to higher Cu level. This indicates that Rv0102 is significant for Cu homeostasis and resistance to Cu toxicity. Knocking out the homologous gene MMAR_0267 in M. marinum (Mm) also enhanced its virulence in zebrafish and improved its survival within macrophages. In THP-1 cells infected with Mm, Mm MMAR_0267 deletion mutants’ intracellular survival increased fourfolds and accompanied by less cell apoptosis. Cu deficiency down-regulates the transcription of the M. marinum virulence factor CFP-10, dampening the STING cytosolic signaling in macrophages, fewer IFN-β and less cell apoptosis. These results suggest that Cu is an important factor in inducing cell apoptosis. In summary, mycobacteria can effectively counteract the host's early key nutritional immune mechanisms by regulating copper metabolism, to increase its virulence.

overall_design: Injected zebrafish with WT, ΔMMAR_0267 and ΔMMAR_0267:: MMAR_0267 M. marinum.  Performed RNA-seq analysis of zebrafish livers.


title: Expression data from MOLT-4 Cells treated with Cannabis extract

status: Public on Jul 12 2023

city: Haifa

first: Elazar

last: Besser

address: Kiryat Hatechnion

institute: Technion

summary: T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematologic tumor, which arises from the malignant transformation of T-cell progenitors. Here we want to understand the influence of Cannabis extracts on T-ALL cells (Molt-4)

overall_design: Total RNA was isolated from MOLT-4 Cells treated with Cannabis extract or vehicle in order to understand gene expression change by cannabis treatment for gene expression profiling using Affymetrix Human Clariom S array

first: David

last: Meiri


title: Immunometabolic effect of nitric oxide on human macrophages challenged with the SARS-CoV2-induced cytokine storm

status: Public on Jul 01 2023

city: Madrid

first: Lisardo

last: Bosca

address: Arturo Duperier 4

department: Metabolism and cellular Signaling

institute: Instituto Investigaciones Biomedicas Alberto Sols

summary: Acute bilateral pneumonia in individuals infected with COVID-19 is the result of a storm of pro-inflammatory cytokines and proteases intensively released by alveolar macrophages, recruiting neutrophils and promoting 'netosis'. Both processes are responsible for the subsequent damage (severe respiratory distress, neutropenia, leukopenia, humoral elevation of inflammation mediators, etc.), which spreads to other organs (thromboembolism, liver, kidney and heart damage). This proposal aims at the administration of inhaled nitric oxide (NO) and NO donors at the systemic level in order to prevent the activation of the innate immune system in the lung, as well as to avoid neutropenia and thromboembolism phenomena, preserving the adaptative immune system function for the benefit of the patient. For this purpose, the immunometabolic properties of human-derived macrophages treated with pro-inflammatory cytokines and an NO donor were evaluated.

overall_design:
mRNA profiles of primary cultures of human monocyte-derived macrophages treated with CK (IL1β, IL-6, IL8, TNFα, IFNƴ and GM-CSF) 20ng/mL for 24h, DETANONOATE 500µM (D500µM) 24h or CK (1h)+DETANONOATE 500µM 24h (D500µM) in RPMI+2%FBS or vehicle (controls RPMI+2%FBS)

**NOTE: the GSM7527763, GSM7527764 sample treatment information has been updated on Oct 13, 2024****

last: Boscá

first: Antonio

last: Castrillo


title: Erythropoietin re-wires cognition-associated transcriptional networks

status: Public on Jun 16 2023

city: Göttingen

first: Hannelore

last: Ehrenreich

address: Hermann-Rein-Str 3

department: Clinical Neuroscience

institute: Max Planck Institute for Multidisciplinary Sciences

summary: Recombinant human erythropoietin (rhEPO) has potent procognitive effects, likely hematopoiesis-independent, but underlying mechanisms and physiological role of brain-expressed EPO remained obscure. Here, we provide transcriptional hippocampal profiling of male mice treated with rhEPO. Based on ~108,000 single nuclei, we unmask multiple pyramidal lineages with their comprehensive molecular signatures. By temporal profiling and gene regulatory analysis, we build developmental trajectory of CA1 pyramidal neurons derived from multiple predecessor lineages and elucidate gene regulatory networks underlying their fate determination. With EPO as ꞌtoolꞌ, we discover populations of newly differentiating pyramidal neurons, overpopulating to ~200% upon rhEPO with upregulation of genes crucial for neurodifferentiation, dendrite growth, synaptogenesis, memory formation, and cognition. Using a Cre-based approach to visually distinguish pre-existing from newly formed pyramidal neurons for patch-clamp recordings, we learn that rhEPO treatment differentially affects excitatory and inhibitory inputs. Our findings provide mechanistic insight into how EPO modulates neuronal functions and networks.

overall_design: C57BL6/N (WT) male mice received 5000 IU/kg i.p. EPO (12 mice) or solvent control (12 mice). Injections go from age P28 to P48, performed every other day for a total of 11 times. Mice are sacrificed 24 h after the last injection, on P49.

first: Manvendra

last: Singh

first: Ying

last: Zhao

first: Vinicius

last: Daguano Gastaldi

first: Sonja

last: Wojcik

first: Yasmina

last: Curto

first: Riki

last: Kawaguchi

first: Ricardo

last: Merino

first: Laura

last: Fernandez Garcia-Agudo

first: Holger

last: Taschenberger

first: Nils

last: Brose

first: Daniel

last: Geschwind

first: Klaus-Armin

last: Nave


title: Gene expression profiles of endothelium, microglia and oligodendrocytes in hippocampus of post-stroke depression rat at single cell resolution

status: Public on May 24 2023

city: Suzhou

first: Yihang

last: Shen

state: Jiangsu

address: 2666 Ludang Road

institute: Suzhou Ninth People's Hospital

summary: Post-stroke depression (PSD) is a common but severe mental complication after stroke. However, the cellular and molecular understanding of PSD is still yet to be illustrated. In current study, we prepared PSD rat model (MD) via unilateral middle cerebral artery occlusion (MCAO) and chronic stress stimulation (DEPR), and isolated hippocampal tissues for single cell sequencing of 10x Genomics Chromium. This study characterized the single cell expression profile of hippocampal PSD, and unmask the differential expressed genes of endothelium, microglia and oligodendrocytes, emphasizing the crosstalk among them to provide theoretical basis for the in-depth mechanism research and drug therapy of PSD.

overall_design: Twenty male adult Sprague Dawley rats aged with 10-12 months (Weight 250-300 g) were randomly divided into two groups (n = 10). These two group were subject to the unilateral intraluminal monofilament in middle cerebral artery for MCAO. One group is then received chronic stress stimulation for depression. Hippocampus tissues in each group (n = 5) were used for single cell sequencing using 10x Genomics platform.

first: Li

last: Cai

first: Hao


title: Systemic coagulopathy promotes host lethality in a new Drosophila model

status: Public on Jun 23 2023

city: Berkeley

first: David

last: Bilder

state: CA

address: 535 Weill Hall

department: Molecular and Cell Biology

institute: University of California, Berkeley

summary: Malignant tumors trigger a complex network of inflammatory and wound repair responses, prompting Dvorak's characterization of tumors as 'wounds that never heal'. Some of these responses lead to profound defects in blood clotting, such as Disseminated Intravascular Coagulopathy (DIC), which correlate with poor prognoses. Here, we demonstrate that a new tumor model in Drosophila provokes phenotypes that recapitulate coagulopathies observed in patients. Fly ovarian tumors overproduce multiple secreted components of the clotting cascade and trigger hypercoagulation of fly blood (hemolymph). Hypercoagulation occurs shortly after tumor induction and is transient; it is followed by a hypocoagulative state such that tumor-bearing flies are defective in wound healing. Hypocoagulation is associated with exhaustion of host clotting components from the body, which is dependent on a tumor-produced clotting factor. Interestingly, clinical studies suggest that lethality in patients with high serum levels of clotting components can be independent of thrombotic events. We show that depleting tumor-produced clotting factors improves survival of tumor-bearing flies, despite the fact that flies have an open circulatory system. Our work establishes a platform for identifying alternative mechanisms by which tumor-driven coagulopathy triggers early mortality, as well as exploring other conserved mechanisms of host responses to chronic wounds.

overall_design: tj-GAL4 tubulinGal80ts and tj-GAL4 tubulinGal80ts; UAS-aPKCΔN UAS-RasV12 ovaries were dissected and dissociated, followed by filtration to enrich for follicle epithelial cells. RNA sequencing was performed on HiSeq4000 platform. At least two biological replicates were sequenced per genotype.

first: Tsai-Ching

last: Hsi

first: Katy

last: Ong

first: Jorian

middle: J

last: Sepers

first: Jung

last: Kim


title: Bulk RNA-seq of human engineered heart tissue for analyzing human myocardial fibrosis

status: Public on Jun 14 2023

city: WUHAN

first: lihang

last: zhu

state: Hubei province

address: HUBEIWUHAN

institute: HUBEIUniversity

summary: Myocardial infarction models developed to understand fibrosis and promote myocardial regeneration towards ischemic heart disease (IHD) is challenged due to the low-throughput nature of in vivo models and the lack of humanized cardiac scarring in the in vitro models. We generated a novel 4D cardiac scarring model (4DCSM) mimicking the IHD in vitro  based on the human engineered heart tissue(hEHT). To identify potential signaling dominating the fibrotic process, we characterized transcriptomics of 4DCSM at different scarring stages by bulk RNA sequencing. Taken together, our dataset is an informative resource to reveal the potential signaling dominating the fibrotic process and provides potential comparisons with public clinical data cohorts or other MI fibrosis model data.

overall_design: The sample was human cardiac scarring model based on the hEHT which derived from human pluripotent stem cells, we collected  three biological replicates of cryoinjured hEHT after 2day and 4day cultivation ,and non-cryoinjured hEHT after 2day and 4day cultivation.

first: Donghui

last: Zhang

first: Pengcheng

last: Yang

first: Lihang

last: Zhu


title: Human engineered heart tissue for analyzing human myocardial fibrosis

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

overall_design: Refer to individual Series


title: Sex bias in autoimmunity is driven by androgen regulation of T cell-intrinsic mechanisms

status: Public on Jun 07 2023

city: Chicago

first: Aly

middle: Azeem

last: Khan

state: IL

address: 6045 S. Kenwood Ave.

institute: University of Chicago

summary: Major autoimmune diseases such as systemic lupus erythematosus (SLE), multiple sclerosis, rheumatoid arthritis and Graves’ disease display a striking female bias, with a female-to-male incidence ratio ranging up to 9:1 in SLE. Sex hormones contribute to protection of males from autoimmunity, but precise molecular mechanisms of such protection are poorly understood. Here, we find that Androgen Receptor (AR), a nuclear receptor regulating a plethora of genes, is active in T cells during development and regulates directly genes involved in T cell activation or indirectly through regulation of other transcription factors. A gene encoding a phosphatase Ptpn22, a negative regulator of T cell receptor signaling, was found to be dependent of the presence of androgen receptor (AR) in males. Castration or deletion of AR reduced expression of Ptpn22. In a mouse model of Systemic Lupus Erythematosus (SLE), Ptpn22 deletion led to the loss of sexual dimorphism. Moreover, analysis of the regulatory regions of Ptpn22 gene revealed a highly conserved sequence that was necessary for upregulation of the gene’s expression by androgens. Mutation of this sequence in Non-Obese Diabetic (NOD) mice led to enhanced ability of T cells to cause Type 1 diabetes. Thus, PTPN22 is likely to participate in disease pathogenesis making it and other AR-regulated genes fair targets for therapeutic interventions in major autoimmune diseases.

overall_design: AR ChIP-seq profiling of murine thymocytes

first: Jean

last: Lee

first: Leonid

last: Yurkovetskiy

first: Alexander

last: Chervonsky


title: scRNA-seq of human engineered heart tissue for analyzing human myocardial fibrosis

summary: Myocardial infarction models developed to understand fibrosis and promote myocardial regeneration towards ischemic heart disease (IHD) is challenged due to the low-throughput nature of in vivo models and the lack of humanized cardiac scarring in the in vitro models. We generated a novel 4D cardiac scarring model (4DCSM)  mimicking the IHD in vitro based on the human engineered heart tissue(hEHT). To identify potential signaling dominating the fibrotic process, we characterized transcriptomics of 4DCSM at different scarring stages by single-cell RNA sequencing. Taken together, our dataset is an informative resource to reveal the critical cell-types fate transformation  and in fibrotic process and provides potential comparisons with public clinical data cohorts or other MI fibrosis model data.

overall_design: The sample was human cardiac scarring model based on based on the hEHT derived from human pluripotent stem cells, we collected three biological replicates of the hEHT after 3day cultivation, cryoinjured hEHT after 2day and 4day cultivation, and non-cryoinjured hEHT after 2day and 4day cultivation.


title: Gene Expression Profiling of Surgically Resectable Soft-Tissue Sarcomas

status: Public on Jun 05 2023

city: Rochester

first: Kim

last: Lauer

state: MN

address: 200 1st St SW

department: Quantitative Health Sciences

institute: Mayo Clinic

summary: For the current study we performed whole genome expression profiling on 69 unique patients with soft-tissue sarcoma who underwent curative-intent surgical resection to identify prognostic gene signatures. Specimens were obtained from the Mayo Clinic Florida STS Biobank and RNA was sequenced using the Tempus xT RNA-seq protocol. This protocol uses transcriptome-capture via more than 415,000 IDT xGen probes spanning greater than 19,000 genes, with at least 50 ng of extracted RNA required before proceeding to library preparation and a minimum depth of 30 million reads a on a NovaSeq 6000. RNA-seq data was analyzed using the MAP-RSeq pipeline developed by Mayo Clinic Bioinformatics Shared Resource.

overall_design: 69 samples obtained from the Mayo Clinic Florida STS Biobank were acquired from patients with soft-tissue sarcoma who underwent curative-intent surgical resection. Gene expression was compared with disease-free and overall survival to identify prognostic gene signatures.

first: Yan

last: Asmann

first: Nathan

last: Seligson


title: Common lymphoid progenitor derivation of plasmacytoid dendritic cells is mediated by Bcl11a

status: Public on Jun 01 2023

city: Austin

first: Alessandra

middle: Machado

last: Araujo

state: TX

address: 2500 Speedway, MBB 3.312B

department: Chemical Engineering

institute: University of Texas at Austin

summary: Plasmacytoid dendritic cells (pDC) specialize in type I interferon production to coordinate innate and adaptive immunity. We identify two pDC subsets in vivo, evaluate their genome-wide expression, and demonstrate a developmental requirement for Bcl11a to provide insight into this enigmatic cell type.

overall_design: Sorted Pdca1+ BM cells from WT naïve C57/BL6 mice and did 10x single cell seq


title: Single-cell co-profiling of gene expression and chromatin accessibility in the mice striatum with varied genetic backgrounds

status: Public on May 11 2023

city: Bar Harbor

first: Christopher

middle: Lee

last: Baker

state: ME

address: 600 Main Street

department: Research

institute: The Jackson Laboratory

summary: To investigate the influence of genetic background and sex on addiction, we conducted a study on the striatum of mice, a crucial brain structure linked to various substance abuse disorders, at the single-cell level. We utilized single-cell multi-omics technology to analyze the gene expression and chromatin accessibility of individual cells in the mice striatum.

overall_design: Mouse striatum were from 8 inbred strains: A/J, C57BL/6J, 129S1/SvImJ, NOD/ShiLtJ, NZO/H1LtJ, CAST/EiJ, PWK/PhJ, and WSB/EiJ. A total of 32 striatum samples were divided in 4 batches, with each batch consisting of 4 male and 4 female samples, and each strain represented in each batch.

first: Wulin

last: Zuo

first: Catrina

last: Spruce

first: Olivier

last: Poirion

first: Brian

last: White


title: tRNA regulation and amino acid usage bias reflect a coordinated metabolic adaptation in Plasmodium falciparum

status: Public on May 14 2023

first: Sherwin

last: Chan

address: Solnavagen 9


title: Effect of Interferon Gamma and Hydroxyproline on Gene Expression in THP-1 Cells

status: Public on May 15 2023

city: SAN DIEGO

first: Stephan

last: Spangenberg

address: 10550 N Torrey Pines Rd, La Jolla, CA 92037

department: Chemistry

institute: The Scripps Research Institute

summary: Hydroxyproline (trans-4-Hydroxy-L-proline) is an abundant amino acid in mammalian tissue, yet little is known about how its prescence effects gene expression. This study aimed to analyze the effects of hydroxyproline on gene expression in THP-1 cells stimulated with IFN-γ, using RNA-seq.

overall_design: RNA-seq analysis was perfromed on samples from THP-1 cells treated for 72 hours with a vehicle control alone, vehicle and IFN-γ (50 ng/ml), or hydroxyproline (40 mM) and IFN-γ were compared. Three replicates per condition were included. Differential gene expression analysis was performed.

first: Amelia

last: Palermo

first: Luke

last: Lairson

first: Gary

last: Siuzdak