title: The interation of CAR-NK cell and tumor cells during the in vivo anti-tumor cell therapy

status: Public on May 25 2022

first: Katayoun

last: Rezvani

department: Department of Stem Cell Transplantation and Cellular Therapy

institute: The University of Texas MD Anderson Cancer Center

summary: Chimeric antigen receptor (CAR) engineering of NK cells is an active area of research with early-phase clinical studies showing an excellent safety profile with encouraging clinical responses. However, the transcriptional signatures that control the fate of CAR-NK cell after infusion and their association with tumor control remain poorly understood. Here, we performed single-cell RNA sequencing (scRNA-seq) to depict the evolution of various engineered CAR-NK cells from the ex vivo infusion products to the in vivo peak phase of tumor control and finally to the relapse phase. Single cell RNA sequencing (scRNA) has revolutionized high-thoughout systems-based analysis of cellular and functional heterogeneity, and dynamic changes in the immune response during the anti-tumor immune cell therapy . The goals of this work are to compare transcriptome profiling (RNA-seq) from both engrafted tumor cells and infused CAR-NK cells over time of treatment course to evaluate the kenetic of tumor cell response and effector functional change of CAR-NK cell. Our study represents the first detailed transcriptomic analysis of using CAR-NK cell therapy aganist Raji-engrafted mouse model. Collecting samples from different time points and organs, the data analysis reported here should privide an envision of the dynamic about how tumor response to immune cell therapy of using CAR-NK cells and also how immune effector fucntion of  CAR-NK cell was modulated over time during the treatment courses.

overall_design: The objective of this study was to investigate the kinetics of function and evolution of adoptively-transferred CAR-NK cells in the context of lymphoma treatment. Of particular interest to us was to determine the impact of IL-15 on the function and persistence of CAR-NK cell and to assess the contribution of IL-15 to NK-mediated anti-tumor activity. To accomplish this, we applied a multi-modal omics approach to characterize pre-infusion NK products and describe the evolution of NK cells post-infusion.

first: Li

last: li


title: Mettl3-mediated m6A modification controls postnatal liver development by modulating Hnf4a-centred regulatory network

city: Guangzhou

first: Yan

last: Xu

state: Guangdong

address: No. 600 Tianhe Road

country: China

institute: The Third Affiliated Hospital of Sun Yat-Sen University

type: Expression profiling by high throughput sequencing

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

overall_design: Refer to individual Series


title: Effect of mesenchymal stem cells on gene expression of fibroblasts when they were co-cultured

status: Public on Jun 03 2022

city: Fuzhou

first: Gui

last: Wu

state: Fujian

address: No. 20 Chazhong Road, Taijing District

department: Department of Orthopedics

institute: First Affiliated Hospital of Fujian Medical University

summary:
Our research and previous reports showed that fibroblasts could inhibit osteoblast differentiation of Mesenchymal stem cells (MSCs). Thus, RNA-seq was carried to analyze the transcriptome differences among fibroblasts cultured alone and fibroblasts co-cultured with MSCs to find detailed mechanisms about how fibroblasts had functions on MSCs.
We then performed gene expression profiling analysis using data obtained from RNA-seq of fibroblasts cultured alone or co-cultured with MSCs.

overall_design: Comparative gene expression profiling analysis of RNA-seq data for mouse embryonic fibroblast cells cultured alone and co-cultured with mouse mesenchymal stem cells.

first: Fei

last: Huang


title: Dose-response hepatic single nuclei RNA sequencing of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) treated mice

status: Public on May 10 2022

city: East Lansing

first: Rance

last: Nault

state: United States

address: 1355 Bogue St. B403

department: Department of Pharmacology and Toxicology

country: USA

institute: Michigan State University

summary: Dose-response is the cornerstone of safety assessments to determine risk. Innovations in transcriptomic technologies has recently led to the ability to profile gene expression at the single-cell level, enabling comprehensive assessment of adaptive and adverse responses at unprecedented resolution. To demonstrate its application of dose dependent study designs, we performed single nuclei sequencing of livers from male C57BL/6 mice gavaged with the persistent environmental contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) at doses of 0.01, 0.03, 0.1, 0.3, 1, 3, 10, or 30 µg/kg or sesame oil vehicle. Following quality control, a total of 131,613 nuclei were sequenced representing 11 distinct cell (sub)types. Our findings reveal dose-dependent changes in relative levels of distinct cell (sub)types such as hepatocytes and macrophages, including the emergence of NASH-associated macrophages (NAMs) characterized by elevated Gpnmb expression. Zonally resolved hepatocytes could also be characterized demonstrating initial induction of aryl hydrocarbon receptor (AhR) target genes such as Cyp1a1 in the central region of the liver lobule while central and portal induction is observed at higher doses. Moreover, we show that zero-inflation inherent to single-cell technologies pose challenges for dose-dependent differential expression analysis and present a novel single-cell Bayesian test method that outperforms common two-group test methods. Collectively, our results demonstrate that single-cell technology can be used to further elucidate mechanisms associated within specific-cell (sub)types and interactions between different cell (sub)types to support the risk assessment paradigm.

overall_design: Male C57BL/6 mice aged postnatal day 28 mice (N = 2-3) were orally gavaged with sesame oil vehicle, 0.01, 0.03, 0.1, 0.3, 1, 3, 10, or 30 μg/kg TCDD every 4 days for 28 days. On day 28 (PND 52) liver samples were immediately collected, frozen in liquid nitrogen, and stored at -80°C. Nuclei were isolated from frozen liver samples, stained with DAPI, and subjected to FACS to generate a single nuclei suspension. Libraries were prepared using the 10X Genomics Single Cell 3' v3.1 kit.

first: Tim

middle: R

last: Zacharewski


title: Transcriptional and functional motifs defining renal function revealed by single nuclear sequencing

status: Public on May 11 2022

city: Boston

first: Yanhui

last: Hu

state: MA

address: 77 Avenue Louis Pasteur

department: Genetics

institute: Harvard Medical School

summary: Like humans, insects rely on precise regulation of their internal environments to survive. The insect renal system consists of Malpighian tubules and nephrocytes that share similarities to the mammalian kidney. Studies of the adult Drosophila Malpighian tubules and nephrocytes have led to many insights in our understanding of stem cell regeneration, protein reabsorption, excretion of waste products, and human kidney diseases. Here, we analyzed single-nucleus RNA sequencing (snRNA-seq) data sets to characterize the cell types of the adult male and female fly kidney.

overall_design: 10x single-nuclei RNA-sequencing of adult Drosophila Malpighian tubules and nephrocytes.  The raw data of Malpighian tubules is part of FCA (https://flycellatlas.org/) and this submission is only relevant to the adult Drosophila nephrocytes which is not available at FCA portal.

first: Jun

first: Yifang

last: Liu

first: Norbert

last: Perrimon


title: The intestine  transcriptome analysis of hybrid yellow catfish  (Tachysurus fulvidraco♀ × P. vachellii♂) under transport stress

status: Public on Jun 18 2022

city: WuXi

first: Tao

last: Zheng

address: No.69, Xuejiali, Nanquan Town, Binhu District, Wuxi City, Jiangsu Province, China

institute: Wuxi Fisheries College, Nanjing Agricultural University

summary: The transport of live fish is a routine operation in aquaculture.     However, the effects of transport stress on intestines gene expression profile is poorly understood.     The results from the transcriptome analysis revealed that most differentially expression genes (DEGs) were enriched in immune and metabolic related signaling pathways.    Toll like receptors is a potential pathway in immune response induced by transport stress.    Changes in genes related to lipid metabolism may be related to the increased metabolic expenditure for the normal body functions in a response to transport stress.    In addition, changes in gene expression in the control, transport, and recovery groups were revealed that transport-induced local immune damage is reversible while metabolic disorder has hysteresis.      These results provide new perspectives on immune and metabolic response in yellow catfish against transport stress and theoretical support for future optimization of their transportation.

sample_organism: Tachysurus fulvidraco x Tachysurus vachelli

overall_design: In this study, hybrid yellow catfish ((Tachysurus fulvidraco♀ * P. vachellii♂) were subjected to simulate the transport (0h, 2h, 4h, 8h, 16h) and recover 96h, and intestinal biochemical and  transcriptome  analyses were performed to broaden our understanding of fish under transport stress.

last: Qiang

first: Yifan

last: Tao

first: Siqi

last: Lu


title: Non-lesional and Lesional Lupus Skin Share Inflammatory Phenotypes that Drive Activation of CD16+ Dendritic Cells

status: Public on Mar 25 2022

city: Los Angeles

first: Feiyang

last: Ma

state: CA

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

department: Molecular Biology Institute

institute: UCLA

summary: Cutaneous lupus erythematosus (CLE) is a disfiguring and poorly understood condition frequently associated with systemic lupus. Studies to date suggest that non-lesional keratinocytes play a role in disease predisposition, but this has not been investigated in a comprehensive manner or in the context of other cell populations. To investigate CLE immunopathogenesis, normal-appearing skin, lesional skin, and circulating immune cells from lupus patients were analyzed via integrated single-cell RNA-sequencing and spatial-seq. We demonstrate that normal-appearing skin of lupus patients represents a type I interferon-rich, ‘prelesional’ environment that skews gene transcription in all major skin cell types and dramatically distorts cell-cell communication. Further, we show that lupus-enriched CD16+ dendritic cells undergo robust interferon education in the skin, thereby gaining pro-inflammatory phenotypes. Together, our data provide a comprehensive characterization of lesional and non-lesional skin in lupus and identify a role for skin education of CD16+ dendritic cells in CLE pathogenesis.

overall_design: Single cell RNA sequencing on lesional and non-lesional lupus skin and healthy normal skin.

first: Allison

middle: C

last: Billi

first: J

middle: M

last: Kahlenberg


status: Public on Apr 11 2022

city: Guelph

first: Roger

last: Moorehead

address: 50 Stone Rd E

department: Biomedical Sciences

country: Canada

institute: University of Guelph

summary: RNA sequencing of MDA-MB-231 cells expressing an empty vector (MDA-231EV), a vector containing the miR-200c/141 cluster (MDA-231c141) or a vector containing the miR-200b/200a/429 cluster

overall_design:
three cell lines, MDA-231EV, MDA-231c141 and MDA-231ba429 with 4 replicates for each cell line
MDA-231EV, MDA-231c141 and MDA-231ba429 cells following injection of the cells into mammary glands of NCG and subsequent mammary tumor development

middle: A


title: Computational identification of preneoplastic cells displaying high stemness and risk of cancer progression

status: Public on Apr 01 2022

city: Beijing

first: Chen

state: Beijing

address: 17 Panjiayuan Nanli

department: Department of Etiology

institute: CAMS Cancer Hospital

summary: Evidence points towards the differentiate state of cells being a marker of cancer risk and progression, in line with the cancer-stem-cell hypothesis. Measuring the differentiation state of single cells in a preneoplastic population could thus enable novel strategies for early detection and risk prediction. Here we present a novel computational method called CancerStemID that estimates a stemness index of cells from single-cell RNA-Seq data. We validate CancerStemID in two human esophageal squamous cell carcinoma (ESCC) cohorts, demonstrating how it can identify undifferentiated preneoplastic cells whose transcriptomic state is overrepresented in invasive cancer. We demonstrate decreased differentiation activity of tissue-specific TFs in cancer cells compared to the basal cell-of-origin layer, and that the differentiation state correlates with differential DNA methylation at the promoters of such TFs independently of underlying NOTCH1 and TP53 mutations. In summary, these data support an epigenetic stem-cell model of oncogenesis and highlight a novel computational strategy in which to identify stem-like preneoplastic cells that undergo positive selection.

overall_design:
We obtained 47 samples derived from 14 treatment-naïve esophageal squamous cell carcinoma (ESCC) patients, including 18 non-tumor tissues (≥5 cm from tumor), 15 dysplasia (≤2 cm to tumor margin), and 14 tumor.   ****Raw sequencing data has been deposited to China Genomic Sequence Archive (GSA) under accession number HRA000776 ****
NOTE FROM SUBMITTER: The raw data in fastq format has been deposited to China Genomic Sequence Archive (GSA) under accession number HRA000776. Due to patient privacy concerns, we can only publish the expression matrix of epithelial cells from de-identified patients.

first: Andrew

middle: E

last: Teschendorff

first: Dongxin

last: Lin

first: Jiang

last: Chang

first: Tianyuan

first: Xuan

last: Zhao

first: Yuan

first: Qi

last: Luo

first: Shaosen

last: Zhang

first: Yiyi

last: Xi

first: Yamei

last: Chen

first: Lin

first: Wenyi

last: Fan

first: Jie

last: Yang

first: Yuling

first: Alok

middle: K

last: Maity

first: Yanyi

first: Jianbin

last: Wang


title: 3D genome organization in the epithelial-mesenchymal transition spectrum [Hi-C]

status: Public on May 08 2022

city: Singapore

first: Tuan Zea

last: Tan

address: 14 Medical Drive, #11-01, Singapore

department: Cancer Science Institute Singapore

country: Singapore

institute: National University of Singapore

summary: Background   The plasticity along the epithelial-mesenchymal transition (EMT) spectrum has been shown to be regulated by various epigenetic repertoires. Emerging evidence of local chromatin conformation changes suggests that regulation of EMT may occur at a higher order of three-dimensional  genome level.  Results  We perform Hi-C analysis and combine ChIP-seq data across cancer cell lines representing different EMT states. We demonstrate that the epithelial and mesenchymal genes are regulated distinctively. We find that EMT genes are regulated within their topologically associated domains (TADs), with only a subset of mesenchymal genes being influenced by A/B compartment switches, indicating topological remodelling is required in the transcriptional regulation of these genes. At the TAD level, epithelial and mesenchymal genes are associated with different regulatory trajectories. The epithelial gene-residing TADs are enriched with H3K27me3 marks in the mesenchymal-like states. The mesenchymal gene-residing TADs , which do not show enrichment of H3K27me3 in epithelial-like states, exhibit increased interaction frequencies with regulatory elements in the mesenchymal-like states.  Conclusions  We propose a novel workflow coupling immunofluorescence and dielectrophoresis to unravel EMT heterogeneity at single-cell resolution. The predicted three-dimensional structures of chromosome 10, harboring Vimentin, identify cell clusters of different states. Our results pioneer a novel avenue to decipher the complexities underlying the regulation of EMT and may infer the barriers of plasticity in the 3D genome context.

overall_design: Hi-C seq profiling of ovarian cancer cell lines PEO1 and HEYA8.

first: Qing

middle: Y

last: Pang

first: Ruby

last: Huang


title: Discerning Biomaterials-driven Transcriptome Dynamics to Induce Mesenchymal Stem Cell Differentiation

status: Public on May 04 2022

city: Bryan

first: Irtisha

last: Singh

state: TX

address: 8447 Riverside Pkwy Medical Research and Education Building II

institute: Texas A&M Health Science Center

summary: Bioactive materials harness the body’s innate regenerative potential by directing endogenous progenitor cells to facilitate tissue repair. Dissolution products of inorganic biomaterials provide unique biomolecular signaling for tissue-specific differentiation. We demonstrate the role of the inorganic biomaterial synthetic two-dimensional (2D) nanosilicates, and its ionic dissolution products on human mesenchymal stem cell differentiation. We utilize whole transcriptome sequencing (RNA-seq), to characterize the contribution of nanosilicates and its ionic dissolution products on endochondral differentiation. Our study highlights the modulatory role of ions in stem cell transcriptome dynamics by regulating lineage-specific gene expression patterns.

overall_design: Examination of effect of nSi and ion dissolution products on hMSC fate

first: Anna

last: Brokesh

first: Lauren

last: Cross

first: Carl

last: Gregory

middle: L

last: Kersey

first: Aparna

last: Murali

first: Christopher

last: Richter

first: Akhilesh

last: Gaharwar


title: Type 2 cytokines in the thymus activate Sirpa+ dendritic cells to promote clonal deletion

status: Public on May 09 2022

city: Minneapolis

first: Kristin

last: Hogquist

state: MN

address: 2101 6th St SE

institute: University of Minnesota

summary: The thymus contains a diversity of dendritic cells (DC) that exist in defined locations and have different antigen processing and presenting features. This suggests that they play non-redundant roles in mediating thymocyte selection. In an effort to eliminate SIRP+ cDC2, we discovered that a substantial proportion expresses the surface lectin, CD301b, in the thymus. These cells resemble the CD301b+ type 2 immune response promoting DC that are present in the skin draining lymph nodes. Transcriptional and phenotypic comparison to other DC subsets in the thymus revealed that thymic CD301b+ cDC represent an activated state that exhibits enhanced antigen processing and presentation. Furthermore, CD301b+ cDC2 demonstrated a type 2 cytokine signature and required steady state IL-4 receptor signaling. Selective ablation of CD301b+ cDC2 impaired clonal deletion without affecting regulatory T cells. TCR alpha repertoire sequencing confirmed that cDC2 promote deletion of conventional T cells with minimal effect on regulatory T cell selection. Together, these findings suggest that cytokine-induced activation of DC in the thymus substantially enforces central tolerance.

overall_design: CD11c and CD11b expressing cells were sorted from the thymus of 7-week-old wildtype (WT) and Mgl2DTR_eGFP treated with diptheria toxin for 48 hours and cells were submitted for scRNA sequencing

first: Elise

last: Breed

first: Matouš

last: Vobořil

first: Katharine

last: Ashby

first: Ryan

middle: J

last: Martinez

first: Lily

last: Qian

first: Haiguang

first: Oscar

last: Salgado

first: Christine

middle: H

last: O'Connor


title: RNA-Seq of Ewing sarcoma shA673-1c cells

status: Public on Mar 10 2022

city: New Orleans

first: Tina

last: O'Grady

state: LA

address: 1430 Tulane Ave., SL79

department: Pathology

institute: Tulane Health Sciences Center

summary: Ewing sarcoma shA673-1c cells were treated with ActD and RNA sequenced to examine RNA stability

overall_design: Three biological replicates of Ewing sarcoma shA673-1c cells were treated with ActD and RNA sequenced at 0h, 1h, 2h and 4h post-treatment

first: Bartimée

last: Galvan

first: Franck

last: Dequiedt


title: Identification of cell types and transcriptome landscapes of PEDV infected porcine small intestine using single-cell RNA-sequencing

status: Public on Apr 27 2022

city: Shanghai

first: shi

last: song

state: Shanghai

institute: Shanghai OE Biotech Co., Ltd

summary: Swine coronavirus-porcine epidemic diarrhea virus (PEDV) with specific susceptibility to pigs has existed for decades, and recurrent epidemics caused by mutant strains have swept the world again since 2010. Here, single-cell RNA-sequencing was used to perform a systematic analysis of pig small intestines infected with PEDV for the first time. Multiple cell types were identified by representative markers, including the unique marker DNAH11 of tuft cells. Meanwhile, the goblet and tuft cells were also susceptible to PEDV except enterocytes. PEDV infection obviously upregulated REG3G, which significantly inhibited virus replication. Notably, IFN-DELTAs in goblet and enterocyte progenitor cells were increased in virus infected piglet, and IFN-DELTA5 could induce GBP1, ISG15, OAS2 and IFITM1 dramatically raised in IPEC-J2 cells and restricted PEDV replication. Complement molecules were mainly expressed in intestinal cells excepting tuft cells, but PEDV decreased C3, C4A, and C5 in enterocytes, thus escaping the antiviral effect of C3. Finally, enterocytes expressed almost all coronavirus entry factors, and PEDV infection caused significant upregulation of the coronavirus receptor ACE2 in porcine enterocyte cells. In summary, this study systematically studied the response of different cell types in small intestine of pigs after PEDV infection, which deepened the understanding of viral pathogenesis.

overall_design: one case jejunum sample from the PEDV infected piglet; one control jejunum sample from the non infected piglet.

first: Baochao

last: Fan

first: Jinzhu

last: Zhou

first: Yongxiang

last: Zhao

first: Xinjian

last: Chang

first: Danyi

last: Shi

first: Jie

last: Yin

first: Rongli

last: Guo

first: Kongwang

last: He

first: Bin

last: Li


title: The MLL-Menin interaction is a molecular dependency in NUP98-rearranged AML [RNA-Seq]

status: Public on Jun 01 2022

first: Scott

last: Armstrong

address: 450 Brookline Ave

department: pediatric oncology

institute: Dana Farber Cancer Institute

summary: Using mouse and human models of NUP98-rearrranged leukemia, we demonstrate that inhibition of MLL-Menin impairs leukemogenic gene expression and  disrupts chromatin binding of MLL1 and NUP98 fusion proteins at a critical subset of genes that is essential for sustaining the undifferentiated leukemia phenotype.

sample_organism:
Homo sapiens
Mus musculus

platform_organism:
Homo sapiens
Mus musculus

overall_design: Examination of gene expression changes in mouse or human leukemia cells treated with the MLL-Menin inhibitor VTP50469

first: Emily

middle: B

last: Heikamp

first: Charlie

last: Hatton


title: IKAROS and MENIN are Functionally Cooperative Therapeutic Targets in Acute Myeloid Leukemia [RNA-seq]

summary: Using RNA-seq we examined the transcriptional changes following IKAROS degradation, MENIN-inhibition or the drug combination in the MOLM13 and MV4;11 human MLL-fusion acute myeloid leukemia cell lines and the CBAM-68552 patient-derived xenograft model.

overall_design: Gene expression changes were assessed in the MOLM13 and MV4;11 human MLL-fusion acute myeloid leukemia cell lines following drug treatment with lenalidomide, CC220, VTP-50469 and the drug combinations. Gene expression changes were assessed in the CBAM-68552 patient-derived xenograft model of acute myeloid leukemia following drug treatment with lenalidomide, VTP-50469 and the drug combinations, compared to vehicle control.

first: Brandon

last: Aubrey


title: IKAROS and MENIN are Functionally Cooperative Therapeutic Targets in Acute Myeloid Leukemia [ChIP-seq]

type: Genome binding/occupancy profiling by high throughput sequencing

summary: Using ChIP-seq we examined the chromatin occupancy of IKAROS, MENIN, MLL1 and MEIS1 in the MOLM13 and MV4;11 human MLL-fusion acute myeloid leukemia cell lines.

overall_design: Chromatin occupancy of IKAROS, MENIN, MLL1 and MEIS1 was assessed in the MOLM13 and MV4;11 human MLL-fusion acute myeloid leukemia cell lines during steady-state growth


title: IKAROS and MENIN are Functionally Cooperative Therapeutic Targets in Acute Myeloid Leukemia [ATAC-seq]

summary: Using ATAC-seq, we examined genome-wide chromatin accessibility in the MOLM13 and MV4;11 human MLL-fusion acute myeloid leukemia cell lines.

overall_design: Chromatin accessibility was assessed in the MOLM13 and MV4;11 human MLL-fusion acute myeloid leukemia cell lines during steady-state growth

first: Jevon

last: Cutler


title: IKAROS and MENIN are Functionally Cooperative Therapeutic Targets in Acute Myeloid Leukemia

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

overall_design: Refer to individual Series


title: Chromatin state changes induced by targeted degradation of MLL-AF9 are phenocopied by combined DOT1L and MENIN inhibition [PRO-seq]

status: Public on Mar 03 2022

summary: Using PRO-seq we examined nascent transcriptional changes and RNA Pol II pausing following MLL-AF9 degradation in MLL-AF9-HA-FKBP12 transformed hCD34+ cells (HCB1) after 15, 30, and 180 minutes

overall_design: Nascent gene expression changes and RNA Pol II pausing were assessed in the MLL-AF9-HA-FKBP12 transformed hCD34+ cells (HCB1) following MLL-AF9 degradation after 15, 30, and 180 minutes of 500nM dTAG-VHL treatment, compared to DMSO control

first: Sarah

middle: N

last: Olsen


title: Chromatin state changes induced by targeted degradation of MLL-AF9 are phenocopied by combined DOT1L and MENIN inhibition [ATAC-seq]

summary: Using ATAC-seq we examined changes in chromatin accessibility following MLL-AF9 degradation in MLL-AF9-HA-FKBP12 transformed hCD34+ cells (HCB1) after 180 minutes.

overall_design: Chromatin accessibility was assessed in the MLL-AF9-HA-FKBP12 transformed hCD34+ cells (HCB1) following MLL-AF9 degradation after 180 minutes of 500nM dTAG-VHL treatment, compared to DMSO control.


title: Chromatin state changes induced by targeted degradation of MLL-AF9 are phenocopied by combined DOT1L and MENIN inhibition.  [ChIP-Seq]

summary: Using ChIP-seq we examined the occupancy changes of various  histone marks and chromatin-bound proteins following accute MLL-AF9 degradation in MLL-AF9-HA-FKPB12 transformed human (HCB1) cells. We also examined occupancy changes of various chromatin-bound proteins in human MLL-AF9-HA-FKBP12 transformed cells (HCB1) and MOLM13 cells in response to DOT1L inhibition, Menin-MLL inhibition, and the combination of DOT1L and Menin-MLL inhibition.

overall_design: We assessed chromatin state changes in human cells (HCB1) following MLL-AF9 degradation. Specifically, human MLL-AF9-HA-FKBP12 cells (HCB1) were treated with 500nM dTAG-VHL or DMSO for 3 hours and 24 hours and chromatin occupancy of various histone marks, members of the MLL-AF9 multi-protein comlex, and the RNA Pol2 machienery was probed. We also assessed chromatin occupancy changes of MLL-AF9 (HA), DOT1L and Menin in the human MLL-AF9-HA-FKBP12 cells (HCB1) after four days of drug treatment with EPZ-5676, VTP-50469, or DMSO control. Lastly, we assessed  MLL-AF9 (HA) and H3K27ac in the human MLL-AF9-HA-FKBP12 cells (HCB1) and MOLM13 cells following four days of drug treatment with EPZ-5676, VTP-50469 and the drug combination, compared to DMSO.


title: IKAROS and MENIN are Functionally Cooperative Therapeutic Targets in Acute Myeloid Leukemia [CUT&RUN]

summary: Using CUT&RUN-seq we examined the chromatin occupancy of IKAROS, H3K27-acetylation and CTCF in steady-state growth conditions. IKAROS chromatin occupancy was also assessed after drug-treatment with CC220, VTP-50469 or the drug combination and compared to a DMSO-vehicle treated control.

overall_design: IKAROS chromatin occupancy was assessed in the MOLM13 and MV4;11 human MLL-fusion acute myeloid leukemia cell lines following drug treatment with CC220, VTP-50469 and the drug combination.


title: Transcriptomic analysis of synovial fibroblasts from monosodium urate crystal-induced arthritis with or without I-BET151 treatment.

status: Public on Feb 17 2022

city: Erlangen

first: Steffen

last: Uebe

address: Kussmaulallee 4

department: Humangenetisches Institut

country: Germany

institute: Uniklinikum Erlangen

summary: We used I-BET 151, an isoxazoloquinoline that specifically inhibits interaction of BET proteins with acetylated histones to restrict inflammatory tissue priming in a mouse model of iterated monosodium urate (MSU) crystal-induced arthritis. Systemic administration of I-BET 151 abolished the enhancement of arthritis upon repeated injection of MSU crystals.

overall_design: Differential gene expression analysis of cultured synovial fibroblasts derived from mouse joints 9 days after the first (non-primed) or the second (primed) injection of monosodium urate (MSU) crytsals with or without treatment with I-BET151 in vitro or in vivo. Three samples from each category (non-primed, primed, primed + treated in vivo, primed + treated in vitro) were used.

first: Markus

last: Hoffmann

first: Philipp

last: Kirchner

first: Arif

last: Ekici


title: Bulk RNA-sequencing Analysis of the Acute Myeloid Leukemia(AML) Malignant Bone Marrow (BM) Infiltrated Tregs

status: Public on Feb 18 2022

city: Charleston

first: Sophie

last: Paczesny

state: South Carolina

address: 86 Jonathan Lucas Street

department: Microbiology & Immunology

institute: Medical University of South Carolina

summary: By RNA-sequencing, we compared four different bone marrow (BM)-derived Tregs, and found that the gene expression profile from No Tumor transplanted group and ST2-KO Tregs tansplanted group shown similar pattern, while WT Treg and Tbet-KO Tregs transplanted group shown the similar trend.

overall_design: WT T conventional cells (Tcon) plus WT Treg transplanted group (No Tumor); WT T conventional cells (Tcon) plus WT Tregs plus MLL-AF9 leukemic cells transplanted group (WT Treg); WT T conventional cells (Tcon) plus ST2-KO Treg plus MLL-AF9 leukemic cells group (ST2-KO Treg);  WT T conventional cells (Tcon) plus Tbet-KO Treg plus MLL-AF9 leukemic cells group (Tbet-KO Treg);

first: Hua

last: Jiang


title: Longitudinal DNA methylation profiling of individuals at baseline and 6 and 12 months following Gender Affirming Hormone Therapy (GAHT)

city: Parkville

first: Boris

last: Novakovic

state: Victoria

address: Murdoch Children's Research Institute, Royal Children's Hospital, Flemington Road

country: Australia

institute: Murdoch Children's Research Institute

summary: In individuals where gender identity and sex assigned at birth are markedly and consistently incongruent, as in the case of transgender people, feminisation or masculinisation may be sought through gender affirming hormone therapy (GAHT). In this study we profiled genome-wide DNA methylation in transgender women and transgender men, before and during GAHT (6 months and 12 months into hormone treatment).

overall_design: Longitudinal blood samples were collected from 13 male-to-female GAHT donors (transwomen) and 13 female-to-male GAHT donors (transmen). Blood was collected at baseline, before hormone therapy started, and 6 months and 12 month after GAHT. Male-to-Female individuals received estrogen therapy, while Female-to-Male individuals received testosterone therapy.

first: Ada

last: Cheung

first: Richard

last: Saffery


title: Chromatin state changes induced by targeted degradation of MLL-AF9 are phenocopied by combined DOT1L and MENIN inhibition.


title: Chromatin state changes induced by targeted degradation of MLL-AF9 are phenocopied by combined DOT1L and MENIN inhibition.  [SLAM-Seq]

summary: Using SLAM-seq we examined the nascent transcriptional changes following MLL-AF9 degradation in MLL-AF9-HA-FKBP12 transformed hCD34+ cells (HCB1) after 15, 30, 60, and 120 minutes

overall_design: Nascent Gene expression changes were assessed in the MLL-AF9-HA-FKBP12 transformed hCD34+ cells (HCB1) following MLL-AF9 degradation after 15, 30, 60, 120 minutes of 500nM dTAG-VHL treatment, compared to DMSO control


title: Single-cell sequencing of mouse peripheral blood mononuclear cells

status: Public on Feb 10 2022

first: Li

last: Jiaxin

address: No.1023,South Shatai Road, Baiyun District

institute: Southern Medical University

summary: Systemic immune cells dysregulation, especially the inflammatory factors over-production plays the pivotal role in sepsis induced abnormalities. We further analyzed how HDCA affects the systemic immune cells during sepsis by employing scRNA-seq for PBMCs.

first: Jiaxin

first: Yuqi

last: Chen

first: Rui

first: Xianglong

last: Zhang


title: MicroRNA profiles of primary breast cancer tumors of systematically untreated and lymph node negative patients

status: Public on Feb 04 2022

city: Odense

first: Ines

last: Block

address: J.B. Winsløws Vej 4

department: Department of Clinical Genetics

country: Denmark

institute: Odense University Hospital

overall_design: Equal amounts of RNA from all included samples were pooled and used as common reference. The analysis was carried out as two-color microarray analysis. Individual samples were labelled with Hy3 and the common reference sample was labelled with Hy5. Hybridization, washing, and scanning (Agilent G2565CA Microarray scanner) were performed according to the recommendations provided by Exiqon.

first: Mark

last: Burton

first: Kristina

middle: P

last: Sørensen

first: Lars

last: Andersen

first: Martin

last: Larsen

last: Bak

first: Søren

last: Cold

first: Mads

last: Thomassen

first: Qihua

last: Tan

first: Torben

last: Kruse


title: 10x BPH sequencing on all cells

status: Public on Feb 16 2022

city: West Lafayette

first: Nadia

middle: Marie

last: Atallah

state: IN

address: 201 S. University St

department: Center for Cancer Research

institute: Purdue University

summary: Single-cell mRNA sequencing (scRNA-seq) study was conducted to to probe heterogeneity of human BPH associated cells. No cell sorting was conducted so all cells within the BPH environment could be represented.

overall_design:
Human BPH tissues were mechanically and enzymatically digested, then debris removed using the Debris Removal Solution (Miltenyi). scRNA-seq was performed for all 5 samples, and 4 out of 5 samples have CITE-seq (cell surface protein expression) data
Please note that the processed data was generated from both CSP and cDNA samples combined (except the '047563_1562-all-cells' sample) and is linked to the corresponding *_cDNA sample records.

first: Renee

last: Vickman

first: Simon

last: Hayward

first: Greg

last: Cresswell

first: Meaghan

last: Broman

first: Omar

last: Franco

first: Timothy

last: Ratliff


title: mRNA-seq of wild-type C. elegans exposed to rotenone

status: Public on Jan 31 2022

city: Durham

first: Kinsey

last: Fisher

state: NC

address: 124 Science Drive

department: Biology

institute: Duke University

summary: To investigate the role of mitochondrial disruption on modulating conserved immunometabolic molecular pathways, we performed a whole transcriptome paired-end mRNA-seq analysis on C. elegans worms exposed to 0.5µM rotenone (a Complex I inhibitor) ,  or vehicle (0.125% dimethyl sulfoxide) . These results revealed 179 differentially expressed genes (134 up, 45 down) enriched for terms such as detoxification, energy metabolism, or pathogen defense. Whole transcriptome data revealed an association with the UPRmt and HIF-1 regulatory pathways.

overall_design: 4 biological replicates of whole-worm mRNA-seq samples collected from wild-type C. elegans exposed to 0.5uM roteneone or vehicle.

first: Danielle

middle: F

last: Mello

first: Christina

last: Bergemann

first: Rojin

last: Chitrakar

first: Shefali

last: Bijwadia

first: Yang

last: Wang

first: Alexis

last: Caldwell

first: L

last: Baugh

first: Joel

last: Meyer


title: Six1 and Six2 of the sine oculis homeobox subfamily are not functionally interchangeable in mouse nephron formation

status: Public on Jan 27 2022

city: New York

first: Aarthi

last: Ramakrishnan

state: New York

address: 1425 Madison Avenue

department: Neuroscience

institute: Icahn School of Medicine at Mount Sinai

summary: The vertebrate Six1 and Six2 arose by gene duplication from the Drosophila so (sine oculis) and have since diverged in their developmental expression patterns. Both genes are expressed in nephron progenitors of human fetal kidneys, and mutations in SIX1 or SIX2 cause branchio-oto-renal or renal hypodysplasia respectively. Since ~80% of SIX1 target sites are shared by SIX2, it is speculated that SIX1 and SIX2 may be functionally interchangeable by targeting common downstream genes. In contrast, in mouse kidneys, the expression of Six1 and Six2 only transiently overlaps in the metanephric mesenchyme before the onset of ureteric branching, and only Six2 expression is maintained in the nephron progenitors throughout development. This non-overlapping expression between Six1 and Six2 in mouse nephron progenitors promoted us to examine if Six1 can replace Six2. Surprisingly, forced expression of Six1 failed to rescue Six2-deficient kidney hypoplasia. We found that Six1 mediated Eya1 nuclear translocation and inhibited premature epithelialization of the progenitors but failed to rescue the proliferation defects and cell death caused by Six2-knockout. Genome-wide binding analyses showed that Six1 only bound to a small subset of Six2 target sites, but many Six2-bound loci that are crucial to the renewal and differentiation of nephron progenitors lacked Six1 occupancy. Thus, these data indicate that Six1 cannot substitute Six2 to drive nephrogenesis in mouse kidneys, demonstrating that these two transcription factors have not maintained equivalent biochemical properties since their divergence early in vertebrate evolution.

overall_design: We performed ChIP-seq in E13.5-14.0 Eya1Six1/+ kidneys to investigate if Six1 targets Six2-bound regulatory regions that are essential for the maintenance of nephron progenitors, as suggested in humans.

first: Jinshu

last: Xu

first: Jun

last: Li

first: Li

last: Shen

first: Pin-Xian


title: RNA-Seq Analysis of Dose-Dependent TCDD-Elicited Ileal Gene Expression in Male Mice

status: Public on Dec 31 2021

city: East Lansing

first: Rance

last: Nault

address: 1355 Bogue St. B403

institute: Michigan State University

summary: Dose-dependent ileal gene expression was examined following repeated exposure (every 4 days for 28 days) to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). These data were used to examine the effect of repeated TCDD exposure on gene expression in the intestinal epithelium of C57BL/6 male mice.

overall_design: Three biological replicates for each dose (3, 10, 30) of TCDD and sesame oil vehicle

first: Kelly

last: Fader

last: Zacharewski


title: WIN site inhibition disrupts a subset of WDR5 function

status: Public on Feb 03 2022

city: Nashville

first: Jing

state: TN

address: 2220 Pierce Avenue

institute: Vanderbilt University Medical Center

summary: This study demonstrates the impact of WIN site inhibitors versus WDR5 degradation on H3K4me and transcriptional processes in human Burkitt's lymphoma cells. We use RNA-seq to measure global transcript levels, ChIP-seq to map genomic H3K4me3, and PRO-seq to map genomic polymerase density and primary transcripts. Our data show that WIN site inhibition disables only a specific subset of WDR5 activity, and that H3K4me changes  induced by WDR5 depletion do not explain accompanying transcriptional responses.

overall_design: Degrade WDR5 rapidly with Auxin (IAA) in AIDW Ramos cells and inhibit WDR5 WIN-site with C16 inhibitor.

first: William

last: Tansey

first: Andrew

last: Siladi

first: Lance

last: Thomas

first: Qi

last: Liu


title: Meningioma DNA methylation grouping reveals biologic drivers and therapeutic vulnerabilities (array)

status: Public on Jan 10 2022

city: San Francisco

first: Abrar

last: Choudhury

state: California

institute: University of California, San Francisco

type: Methylation profiling by genome tiling array

summary: We report DNA methylation profiling on 565 meningiomas integrated with genetic, transcriptomic, biochemical, proteomic, and single-cell approaches to show meningiomas are comprised of 3 groups with distinct clinical outcomes, biological drivers, and therapeutic vulnerabilities. Merlin-intact meningiomas have the best outcomes and are distinguished by NF2/Merlin regulation of glucocorticoid signaling, apoptosis, and susceptibility to cytotoxic therapy. Immune-enriched meningiomas have intermediate outcomes and are distinguished by immune infiltration, HLA expression, and lymphatic vessels. Hypermitotic meningiomas have the worst outcomes and are distinguished by convergent genetic and epigenetic mechanisms driving the cell cycle and resistance to cytotoxic therapy. Our results establish a framework for understanding meningioma biology, and provide a foundation for new meningioma treatments.

overall_design: DNA methylation profiles of 565 meningiomas collected between 1991 and 2019 at two international institutions

first: David

last: Raleigh


title: Pseudoautosomal region 1 overdosage affects the global transcriptome in iPSCs from patients with Klinefelter syndrome and high-grade X chromosome aneuploidies

city: Jeddah

first: Antonio

last: Adamo

state: Not in US

address: 4700 KAUST, Thuwal

department: Biological and Environmental Science and Engineering Division, BESE

country: Saudi Arabia

institute: King Abdullah University of Science and Technology, KAUST

summary: Klinefelter syndrome (KS) is the most prevalent aneuploidy in males and is characterized by one or more supernumerary X chromosomes. Here, using a paradigmatic cohort of KS-inducible pluripotent stem cells (iPSCs) carrying 49-XXXXY, 48-XXXY, and 47-XXY karyotypes, we identified genes within the pseudoautosomal region 1 (PAR1) region as the most susceptible to dosage-dependent transcriptional dysregulation and therefore potentially responsible for the progressively worsening phenotype in higher grade X aneuploidies. By contrast, biallelically expressed non-PAR escape genes displayed high interclonal and interpatient variability in iPSCs and differentiated derivatives, suggesting that these genes could be associated with variable KS traits. By interrogating KS-iPSCs at single-cell resolution, we showed that PAR1 and non-PAR escape genes were not only resilient to X-inactive specific transcript (XIST)-mediated inactivation but also that their transcriptional regulation was disjointed from the absolute XIST expression level. Finally, we explored the transcriptional effects of X chromosome overdosage on autosomes and identified the transcription factor nuclear respiratory factor 1 as the master regulator of zinc finger protein X-linked. Our findings provided the first evidence of an X-dosage-sensitive autosomal transcription factor regulating an X-linked gene in low- and high-grade X aneuploidies.

overall_design: Bulk transcriptomic profiles of iPSC derived from Klinefelter syndrome patients and controls. The cohort includes low and high grade KS clones. For each patient two or three independent clones have been generated and for each clone two or three independent RNA-Seq libraries have been processed

first: Veronica

last: Astro

first: Maryam

last: Alowaysi

first: Elisabetta

last: Fiacco

first: Alfonso

last: Sierra

last: Londono

first: Riccardo

last: Cigliano


title: Meningioma DNA methylation grouping reveals biologic drivers and therapeutic vulnerabilities

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

overall_design: Refer to individual Series


title: RNA sequencing of meningiomas

summary: We report RNA sequencing of 185 meningiomas, which are used to interrogate the biology underlying DNA methylation groups of meningioma.

overall_design: mRNA profiles of 185 meningiomas collected between 1991 and 2019 at one institution


title: Single-cell RNA sequencing of meningiomas

summary: We report single-cell RNA sequencing of 57,114 cells from 8 meningioma samples and 2 dura samples, which are used to analyze the inter- and intra-meningioma heterogeneity across DNA methylation groups.

overall_design: A total of 10 tissue samples from 6 meningioma patients were analyzed. Two patients had 2 pieces each of their meningiomas analyzed, one from the bulk of the tumor and another from the brain-tumor interface (BTI). 2 patients also had dura tissue from their meninges analyzed as well as a normal tissue control.


title: Single-cell RNAseq by Dropseq of retinal endothelial cells from WT and ENOS KO mouse

status: Public on Jan 02 2022

city: Montréal

first: Gael

middle: Louis Max

last: Cagnone

state: QC

address: 3175 Chemin de la Côte-Sainte-Catherine

department: The Montreal single-cell Academy

institute: CHU Sainte Justine

summary: We report the generation of single-cell RNAseq data obtained using Drop-seq from endothelial-enriched retinal cell suspension. Single-cell suspension were enriched using CD-31 antibody coated magnetic beads, and processed for encapsulation and library preparation as in Macosko et al (Cell 2015) based on the Drop-seq procedure.

overall_design: Retinas were digested as in Macosko et al (Cell 2015), and single-cell suspensions were prepared from P14 OIR eNOS+/+ (C57BL/6) and eNOS-/- mouse retinas (n=3 replicates per genotype, with 3-5 retina pooled per replicate). The final EC suspension was obtained by positive enrichment using beads coated with CD31 antibodies and magnetic columns. For single-cell RNA-seq of ECsendothelial-enriched retinal cell suspension, droplet generation and cDNA libraries were performed as described in the Drop-seq procedure (http://mccarrolllab.org/dropseq/), and sequencing was carried out on an Illumina NextSeq 500 at an estimated read depth/cell similar to that used by Macosko et al. (i.e., 50,000 reads/cell). Unique molecular identifier (UMI) counts associated with aligned reads (kb-python, GRCm38 reference genome) from the scRNA-seq replicates of eNOS+/+ and eNOS-/- retina were merged into one single digital gene expression (DGE) matrix and processed using the “Seurat” package (spatial reconstruction of single-cell gene expression data [28]). Cells expressing fewer than 100 genes and more than 10% of mitochondrial genes were filtered out. Single-cell transcriptomes were normalized by dividing by the total number of UMIs per cell and then multiplying by 10,000. All calculations and data were then performed in log space [i.e., ln(transcripts per 10,000 + 1)].  After integrating of the different biological replicates using the Seurat anchor integration algorithm, the 20 most significant components were used as input for dimensionality reduction and clustering. To identify putative cell types from the Uniform Manifold Approximation and Projection (UMAP) dimensional reductions, a graph-based clustering approach using K-nearest neighbor graph and the Louvain algorithm was used to define clusters and average gene expression was computed for each of the identified cluster based on Euclidean distances.  Marker genes that were significantly enriched for each cluster were then identified, allowing cluster annotation to specific cell types. A similar computational approach was performed on non-integrated RNA data to sub-cluster the population of ECs, allowing us to define 3 cell subtypes based on marker genes. After removing the contaminant cell cluster (i.e., red blood cells and retinal pigmented epithelium), a total of 3031 cells were obtained from eNOS+/+ retina (including 2044 ECs) and 5913 cells from eNOS-/- retina (including 3334 ECs).

first: Tracy

last: Smith

first: Gregor

middle: U

last: Andelfinger

first: Jean-Sébastien

last: Joyal

first: Jean-Philippe

last: Gratton


title: Action of WDR5 and HDM2 inhibitors in SMARCB1-deficient cancer cells

first: Jing

last: Wang

summary: Rhabdoid tumors (RT) are rare and aggressive pediatric tumors that are driven by the loss the tumor suppressor SNF5 (SMARCB1). Here we examine how RT cells respond to small molecule-mediated inhibitors of the “WIN” site of WDR5, a chromatin-associated protein that regulates a specific set of genes linked to protein synthesis. We characterize WDR5 binding in RT cell lines via ChIP-Seq and show that WIN site inhibitor rapidly and comprehensively displaces WDR5 from chromatin in these cells. Using Precision Run On-sequencing (PRO-Seq) we show that WDR5-bound protein synthesis genes are early and direct transcriptional targets of WIN site inhibitor. We also use RNA-Seq to characterize the persistent transcriptional changes in RT lines treated with WIN site inhibitor, and compare these transcriptional effects with those of the HDM2 inhibitor nutlin-3a.

overall_design: G401, TTC642, KYM-1, TTC549, or TM87-16 cells were treated with DMSO or WIN site inhibitor C16. ChIP-Seq was used to track interaction of WDR5 with chromatin; PRO-Seq was used to track early changes in the distribution of active RNA polymerases, and RNA-Seq was used to monitor long-term transcriptional changes. RNA-Seq was also performed on G401, TTC642, and KYM-1 cells treated with the HDM2 inhibitor nutlin-3a

first: William

last: Tansey

first: Andrea

last: Wojciechowski

first: April

last: Weissmiller


title: Gene expression analyses in murine proepicardial and epicardial cells

status: Public on Dec 20 2021

city: Granada

first: Francisco

last: Hernandez-Torres

state: Granada

address: Avda. de la Investigación, 11

department: Dept. of Biochemistry, Molecular Biology III and Immunology

country: Spain

institute: Universidad de Granada

type: Non-coding RNA profiling by high throughput sequencing

summary: We provide herein a transcriptomic analyses of mouse embryonic day 9.5 proepicardial cells, isolated from Wt1CreEGFP mice and mouse embryonic day 10.5 FACS-sorted embryonic epicardial cells also from Wt1CreEGFP mice. Distinct libraries were constructed to performed microRNA and mRNA/lncRNAs sequencing, respectively. Data comparison allowed us to identify 1876 differentially expressed mRNAs, 171 lncRNAs and 68 microRNAs.

overall_design: Examination of the transcriptome in mouse proepicardial and epicardial cells.

first: Diego

last: Franco

last: Hernandez Torres

first: Estefania

last: Lozano Velasco

first: Juan

last: Castillo Casas

first: Angel

last: Dueñas Lechuga

first: Amelia

last: Aranega Jimenez


title: Chromatin state changes induced by targeted degradation of MLL-AF9 are phenocopied by combined DOT1L and MENIN inhibition. [RNA-Seq]

city: Boston

first: Scott

last: Armstrong

state: MA

summary: Using RNA-seq we examined the transcriptional changes following MLL-AF9 degradation in MLL-AF9-HA-FKPB12 transformed murine (BM2222) and human (HCB1) cells. We also examined transcriptional changes in human MLL-AF9-HA-FKBP12 transformed cells (HCB1) and MOLM13 cells in response to DOT1L inhibition, Menin-MLL inhibition, and the combination of DOT1L and Menin-MLL inhibition. Lastly we assessed gene expression in  murine neutrophils isolated directly from mice.

overall_design: Gene expression changes were assessed in MLL-AF9-HA-FKBP12 transformed murine (BM2222) and human cells (HCB1) following MLL-AF9 degradation. Specifically, murine MLL-AF9-HA-FKBP12 cells (BM2222) were treated with 500nM dTAG-13 for 3 hours, 24 hours, and 5 days and gene expression was compared to DMSO control. Similarly, human MLL-AF9-HA-FKBP12 cells (HCB1) were treated with 500nM dTAG-VHL for 3 hours, 24 hours, and 5 days and  gene expressoin was compared to DMSO control. Gene expression changes were also assessed in the human MLL-AF9-HA-FKBP12 cells (HCB1) and MOLM13 cells following drug treatment with EPZ-5676, VTP-50469 and the drug combination at the indicated timepoints. Lastly, murine neutrophils were isolated from murine bone marrow to assess gene expression in neutrophils.

first: Sarah

last: Olsen

first: Charlie

last: Hatton


title: Induction of T cell dysfunction and NK-like T cell differentiation in vitro and in patients after CAR T cell treatment [scRNA-seq KO]

status: Public on Dec 06 2021

city: Philadelphia

first: Gregory

last: Donahue

state: PA

address: 3400 Civic Center Blvd, Bldg 421

department: Cell & Developmental Biology

institute: The University of Pennsylvania

summary: Chimeric antigen receptor (CAR) T cell therapy has achieved remarkable success in hematological malignancies but remains largely ineffective in solid tumors. A major factor leading to the reduced efficacy of CAR T cell therapy is T cell dysfunction, and the mechanisms mediating this dysfunction are under investigation. Here we establish a robust in vitro model to study mesothelin-redirected CAR T cell dysfunction in pancreatic cancer. Continuous antigen exposure results in hallmark features of exhaustion including reduced proliferation capacity and cytotoxicity, and severe defects in cytokine production. Here we identified a transcriptional signature at both population and single-cell levels in CAR T cells after chronic antigen exposure. In addition, TCR lineage tracing revealed a CD8+ T-to-NK-like T cell plasticity that results in reduced antigen- dependent tumor cell killing. The transcription factors SOX4 and ID3 are specifically expressed in the dysfunctional CAR NK-like T cells and are predicted to be master regulators of the dysfunction gene expression signature and of the post-thymic acquisition of an NK-like T cell fate. Finally, we identified the emergence of CAR NK-like T cells in a subset of patients after infusion of CAR T cells. The findings gleaned from this study reveal new approaches to improve the efficacy of CAR T cell therapy in solid tumors by preventing or revitalizing CAR T cell dysfunction and shed light on the plasticity of human CAR T cells.

overall_design: Examines expression by single-cell RNA-seq in CD8+ T cells from two donors. Genetic background varies, contrasting Sox4 and ID3 knockouts vs WT. All samples are continuously exposed to antigen. Only one donor has the Sox4 knockout mutation.

first: Shunichiro

last: Kuramitsu

first: Charly

middle: R

last: Good

first: Parisa

last: Samareh

first: Greg

first: Kenichi

last: Ishiyama

first: Yujie

last: Ma

first: Nils

last: Wellhausen

first: Lifeng

last: Tian

first: Sangya

last: Agarwal

first: Sonia

last: Guedan

first: M

last: Aznar

first: Katherine

last: Alexander

first: Zhen

last: Zhang

first: Nathan

last: Singh

first: Max

middle: W

last: Richardson

first: Keisuke

last: Watanabe

first: Janos

last: Tanyi

first: Mark

last: O'Hara

first: Marco

last: Ruella

first: Simon

last: Lacey

first: Edmund

last: Moon

first: Stephen

last: Schuster

first: Steven

last: Albelda

first: Lewis

last: Lanier

first: Regina

last: Young

first: Shelley

last: Berger

first: Carl

last: June


title: Single cell RNA-sequencing of Tumor-Associated High Endothelial Cells (TA-HECs) and comparison to their counterparts in homeostatic and inflamed mouse lymph nodes

status: Public on Dec 14 2021

city: Toulouse

first: Juliette

last: Coudert

address: 205 route de Narbonne

country: France

institute: CNRS

summary: High endothelial venules (HEVs) are specialized postcapillary venules that mediate lymphocyte trafficking from the blood into lymph nodes. HEV-like blood vessels are found in solid tumors in association with CD8+ T cell infiltration.This study uses single cell RNA-sequencing using the Fluidigm C1 system as a method to evaluate the transcriptome in lymph node and tumor-associated HEV endothelial cells (LN-HECs and TA-HECs). We isolated MECA-79+ TA-HECs and CD31+MECA-79- tumor-associated endothelial cells (TA-ECs) by cell sorting and we compared their transcriptome to those of their counterparts in homeostatic (LN-HECs and LN-ECs) or inflamed (iLN-HECs) lymph nodes. TA-HECs express high levels of endothelial cell markers Cdh5 and Pecam1 (CD31), post-capillary venule marker Ackr1 (DARC) and venous transcription factor Nr2f2, indicating that they correspond to post-capillary venule endothelium, like their lymph node counterparts. The genes encoding HEV sialomucins decorated by the sulfated MECA-79 epitope (CD34 and Emcn, endomucin) and the core 1 branching enzyme B3gnt3 that is essential for its biosynthesis, are equally expressed in all HEC populations, whereas sulfotransferases Chst2 and Chst4 are expressed at lower levels in TA-HECs. Although TA-HECs are molecularly distinct from lymph node HECs, they share several important characteristics with iLN-HECs, including the upregulation of endothelial selectins (Selp, Sele) and inflammatory chemokines CXCL9 and CXCL10, the ligands for chemokine receptor CXCR3 on effector T cells. Finally, endothelial cell adhesion molecules ICAM1, ICAM2 and VCAM1 that are important for lymphocyte sticking to HEVs, are expressed at similar levels in all HECs. Together, these findings indicated that MECA-79+ TA-HECs, similar to HECs in immune-stimulated lymph nodes, exhibit an inflamed phenotype characterized by co-expression of MECA-79+ antigens with endothelial selectins and inflammatory chemokines.

overall_design:
Comparison of Tumor-Associated High Endothelial Cells (TA-HECs) and blood Endothelial Cells (TA-bECs) with their lymph node counterparts (HHECs, IHECs, BECs) with a total of 257 single cells.
HHECs, IHECs, BECs were previously submitted to GEO in GSE106514

first: Claire

last: Tardiveau

first: Krystle

last: Veerman

first: Jean-Philippe

last: Girard


title: Genome-wide Analysis of Sp6/Epiprofin DNA Binding Sites in the Developing Mouse Molar Using ChIP-seq Analysis

status: Public on Nov 23 2021

city: Bethesda

first: Yasuo

last: Yoshitomi

state: MD

address: 30 Convent Dr.

department: NIDCR

institute: NIH

summary:
In this study, whole-genome ChIP-seq analysis was performed to identify Sp6 regulatory targets from postnatal mouse molars. Enriched sequence reads (peaks) from Sp6 immunoprecipitations were located predominately adjacent to transcriptional start sites. Notably enriched for Sp6 peaks were genes highly-expressed in the tooth. Bioinformatic analysis of two pools of 1400 Sp6 enriched sequences identified a consensus nine-nucleotide DNA pulldown sequence of CTg/aTAATTA from mesenchyme and the nearly identical sequence, CTa/gTAATTA, from epithelium. Sp6 AT-rich interaction sequences are nearly identical to the ChIP-seq enriched sequences reported for Sp7 and Sp9. ChIP-seq analysis indicates Sp6 regulates a significant number of genes expressed in the tooth.

GSE145909 is the original submission. GSE151391 is also from the same study.
https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE151391

overall_design: Analysis of Sp6 DNA binding in dental epithelium and dental mesenchyme using ChIP-seq analysis

first: Craig

middle: S

last: Rhodes

first: Nowlan

last: Freese

first: Takashi

last: Nakamura

first: Yuta

last: Chiba

first: Yoshihiko

last: Yamada


title: Histone ChIP-seq from middle frontal area 46 (ENCSR931QOV)

status: Public on Nov 04 2021

city: Stanford

first: ENCODE

last: DCC

state: CA

address: 300 Pasteur Dr

institute: ENCODE DCC

summary:
H3K27me3 ChIP-seq on middle frontal area 46 tissue female adult (85 years) with Alzheimer's disease.

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


title: Induction of T cell dysfunction and NK-like T cell differentiation in vitro and in patients after CAR T cell treatment

first: Gregory

last: Donahue


title: Stem cells expand potency and alter tissue fitness by accumulating diverse epigenetic memories (scRNA-seq)

status: Public on Nov 29 2021

first: Kevin Andrew

middle: Uy

last: Gonzales

state: NY

address: 1230 York Avenue

institute: The Rockefeller University

summary: Immune and tissue stem cells retain an epigenetic memory of inflammation that intensifies sensitivity to future encounters. Here, we address whether and to what consequence stem cells possess and accumulate memories of diverse experiences. Monitoring a choreographed response to wounds, we find that as hair follicle stem cells leave their niche, migrate to repair damaged epidermis and take up long-term foreign residence there, they accumulate long-lasting epigenetic memories of each experience, culminating in post-repair epigenetic adaptations that sustain the epidermal transcriptional program and surface barrier. Each memory has its own physiological impact, collectively endowing these stem cells with heightened regenerative ability to heal wounds and broadening their tissue regenerating tasks compared to their naïve counterparts. These findings have profound implications for tissue fitness and aging.

overall_design: We use single cell RNA-seq technology to delineate transcriptional states across homeostatic, wound-induced and niche-adapted stem cell populations in the skin in vivo. Temporal analysis reveals key genes that change over time as cells initiate and resolve plasticity, and as cells adapt to a new microenvironment.

first: Kevin-Andrew

first: Elaine

last: Fuchs


title: Histone ChIP-seq from middle frontal area 46 (ENCSR928SPE)

summary:
H3K4me3 ChIP-seq on middle frontal area 46 tissue female adult (90 or above years) with mild cognitive impairment

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


title: Histone ChIP-seq from middle frontal area 46 (ENCSR929TOD)

summary:
H3K4me3 ChIP-seq on middle frontal area 46 tissue female adult (90 or above years) with Alzheimer's disease.

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


title: RNA-sequencing of tumor infiltrating cells across 12 different solid tumors type

status: Public on Dec 29 2021

first: Bushra

last: Samad

address: 505 Parnassus Ave

institute: USCF Immunoprofiler

summary: To identify patterns of gene expression within six broadly defined cell   populations, we also performed cell sorting for bulk RNA-sequencing including compartments denoted: 1. “Live”: All viable cells at the time of sorting, 2. “Tconv”: sorted conventional CD4+ and CD8+ T cells, 3. “Treg”: CD25+ CD4+ (enriched for regulatory) T cells, 4. “Myeloid”: Lymphocyte-negative HLA-DR+ (enriched for myeloid) cells, 5. “Stromal”: CD45- CD44+Thy1+ cells, and 6. “Tumor”: all other CD45- cells

overall_design: Tumor samples for the Immunoprofiler was transported from various cancer operating rooms (ORs) as well as from outpatient clinics. All patients consented by the UCSF IPI clinical coordinator group for tissue collection under a UCSF IRB approved protocol (UCSF IRB# 20-31740). Tumor or metastatic tissue was thoroughly chopped with surgical scissors and transferred to GentleMACs C Tubes (Miltenyi Biotec) containing 20 uL/mL Liberase TL (5 mg/ml, Roche) and 50 U/ml DNAse I (Roche) in RPMI 1640 per 0.3 g tissue. GentleMACs C Tubes were then installed onto the GentleMACs Octo Dissociator (Miltenyi Biotec) and incubated for 45min according to the manufacturer’s instructions. Samples were then quenched with 15 mL of sort buffer (PBS/2% FCS/2mM EDTA), filtered through 100 um filters and spun down. Red blood cell lysis was performed with 175 mM ammonium chloride if needed.   Cells were then incubated with Human FcX (Biolegend) to prevent non-specific antibody binding. Cells were then washed in DPBS and incubated with Zombie Aqua Fixable Viability Dye (Thermo). Following viability dye, cells were washed with sort buffer and incubated with cell surface antibodies mix diluted in the BV stain buffer (BD Biosciences) following manufacturer instruction for 30 minutes on ice in the dark and subsequently fixed in either Fixation Buffer (BD Biosciences) or in Foxp3/Transcription Factor Staining Buffer Set (eBioscience) if intracellular staining was required.

first: Alexis

last: Combes

first: Matthew

last: Krummel


title: Histone ChIP-seq from middle frontal area 46 (ENCSR668QQL)


title: Histone ChIP-seq from middle frontal area 46 (ENCSR832EJX)

summary:
H3K27me3 ChIP-seq on middle frontal area 46 tissue female adult (86 years) with Alzheimer's disease.

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


title: Histone ChIP-seq from middle frontal area 46 (ENCSR662MZX)

summary:
H3K27me3 ChIP-seq on middle frontal area 46 tissue female adult (90 or above years) with mild cognitive impairment

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


title: Histone ChIP-seq from middle frontal area 46 (ENCSR979OTM)

summary:
H3K27me3 ChIP-seq on middle frontal area 46 tissue female adult (90 or above years).

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


title: Histone ChIP-seq from middle frontal area 46 (ENCSR916DKK)

summary:
H3K27me3 ChIP-seq on middle frontal area 46 tissue female adult (83 years)

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


title: Histone ChIP-seq from middle frontal area 46 (ENCSR662BVK)

summary:
H3K4me3 ChIP-seq on middle frontal area 46 tissue female adult (87 years)

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


title: Histone ChIP-seq from middle frontal area 46 (ENCSR706XFG)


title: Histone ChIP-seq from middle frontal area 46 (ENCSR653OJO)

summary:
H3K27me3 ChIP-seq on middle frontal area 46 tissue female adult (88 years) with mild cognitive impairment

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


title: Histone ChIP-seq from middle frontal area 46 (ENCSR639RKS)


title: Histone ChIP-seq from middle frontal area 46 (ENCSR584RKY)


title: Histone ChIP-seq from middle frontal area 46 (ENCSR585UDE)

summary:
H3K4me3 ChIP-seq on middle frontal area 46 tissue female adult (83 years)

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


title: Histone ChIP-seq from middle frontal area 46 (ENCSR443JIO)

summary:
H3K4me3 ChIP-seq on middle frontal area 46 tissue female adult (86 years) with Alzheimer's disease.

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


title: Histone ChIP-seq from middle frontal area 46 (ENCSR580RIQ)

summary:
H3K4me3 ChIP-seq on middle frontal area 46 tissue female adult (90 or above years).

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


title: Histone ChIP-seq from middle frontal area 46 (ENCSR545ZQT)

summary:
H3K4me3 ChIP-seq on middle frontal area 46 tissue female adult (85 years) with Alzheimer's disease.

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


title: A Growth Factor-Expressing Macrophage subpopulation orchestrates regenerative inflammation via GDF-15

status: Public on Nov 16 2021

first: Laszlo

last: Halasz

address: 1470 Madison Avenue

department: Department of Oncological Sciences

institute: Mount Sinai Icahn School of Medicine

summary: Muscle regeneration is the result of the concerted action of multiple cell types driven by the temporarily controlled phenotype switches of infiltrating monocyte-derived macrophages. Proinflammatory macrophages transition into a phenotype that drives tissue repair through the production of effectors such as growth factors. This orchestrated sequence of regenerative inflammatory events, which we termed Regeneration-Promoting Program (RPP), is essential for proper repair. However, it is not well understood how specialized repair-macrophage identity develops in the RPP at the transcriptional level and how induced macrophage-derived factors coordinate tissue repair. Gene expression kinetics-based clustering of blood circulating Ly6Chigh, infiltrating inflammatory Ly6Chigh, and reparative Ly6Clow macrophages, isolated from injured muscle, identified the TGF-beta superfamily member, GDF-15, as a component of the RPP. Myeloid GDF-15 is required for proper muscle regeneration following acute sterile injury, as revealed by gain- and loss-of-function studies. Mechanistically, GDF-15 acts both on proliferating myoblasts and muscle-infiltrating myeloid cells. Epigenomic analyses of upstream regulators of Gdf15 expression identified that it is under the control of nuclear receptors RXR/PPARg. Finally, immune single-cell RNA-seq profiling revealed that Gdf15 is coexpressed with other known muscle regeneration-associated growth factors, and their expression is limited to a unique subpopulation of repair-type macrophages (Growth Factor-Expressing Macrophages, GFEM).

overall_design: Time-dependent profiles were recapitulated in sorted blood monocytes, Ly6Chigh and Ly6Clow muscle macrophages following cardiotoxin injury.

last: Nagy

first: Andreas

last: Patsalos


title: Histone ChIP-seq from middle frontal area 46 (ENCSR313IJX)

summary:
H3K4me3 ChIP-seq on middle frontal area 46 tissue female adult (88 years) with mild cognitive impairment

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


title: Histone ChIP-seq from middle frontal area 46 (ENCSR558GCO)

summary:
H3K27me3 ChIP-seq on middle frontal area 46 tissue female adult (87 years)

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


title: Histone ChIP-seq from middle frontal area 46 (ENCSR386KFO)

summary:
H3K4me3 ChIP-seq on middle frontal area 46 tissue female adult (89 years) with Alzheimer's disease

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


title: Histone ChIP-seq from middle frontal area 46 (ENCSR274HDQ)

summary:
H3K4me3 ChIP-seq on middle frontal area 46 tissue female adult (90 or above years)

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


title: Histone ChIP-seq from middle frontal area 46 (ENCSR899PMX)

summary:
H3K27me3 ChIP-seq on middle frontal area 46 tissue female adult (90 or above years) with Alzheimer's disease.

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


title: Histone ChIP-seq from middle frontal area 46 (ENCSR340FUG)


title: Histone ChIP-seq from middle frontal area 46 (ENCSR060MAU)

summary:
H3K4me3 ChIP-seq on middle frontal area 46 tissue female adult (90 or above years) with mild cognitive impairment.

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


title: Histone ChIP-seq from middle frontal area 46 (ENCSR052ETC)

summary:
H3K27me3 ChIP-seq on middle frontal area 46 tissue female adult (90 or above years) with mild cognitive impairment.

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


title: Histone ChIP-seq from middle frontal area 46 (ENCSR250CLO)


title: Histone ChIP-seq from middle frontal area 46 (ENCSR190FSS)

summary:
H3K27me3 ChIP-seq on middle frontal area 46 tissue female adult (90 or above years) with Alzheimer's disease, Cognitive impairment.

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


title: Histone ChIP-seq from middle frontal area 46 (ENCSR235BES)

summary:
H3K4me3 ChIP-seq on middle frontal area 46 tissue female adult (88 years) with Alzheimer's disease.

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


title: Histone ChIP-seq from middle frontal area 46 (ENCSR334FVC)

summary:
H3K27me3 ChIP-seq on middle frontal area 46 tissue female adult (90 or above years).

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


title: Histone ChIP-seq from middle frontal area 46 (ENCSR314KSZ)


title: Histone ChIP-seq from middle frontal area 46 (ENCSR346PKZ)


title: Histone ChIP-seq from middle frontal area 46 (ENCSR128YOH)

summary:
H3K4me3 ChIP-seq on middle frontal area 46 tissue female adult (79 years).

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


title: Histone ChIP-seq from middle frontal area 46 (ENCSR064PTX)

summary:
H3K27me3 ChIP-seq on middle frontal area 46 tissue female adult (89 years) with Alzheimer's disease

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


title: Comparative bulk RNAseq analysis of cultured single-clone WT (P23) and p53-deleted (cKO, P28 and P4M) skeletal cells in bone marrow

status: Public on Oct 16 2021

city: Houston

first: Noriaki

last: Ono

state: Texas

department: School of Dentistry

institute: University of Texas Health Science Center at Houston

summary: we revealed the cellular mechanisms underlying the tumorigenicity of skeletal cells.

overall_design: tdTomato+ cells were cultured for 8 passages from Fgfr3creER; R26R-tdTomato (WT, P23) and Fgfr3creER; Trp53fl/fl; R26R-tdTomato (cKO, P28 and P4M) femur bone marrow. Tamoxifen was injected at P21. cDNA were sequenced by Illumina NovaSeq 6000


title: Histone ChIP-seq from middle frontal area 46 (ENCSR169CRN)

summary:
H3K4me3 ChIP-seq on middle frontal area 46 tissue female adult (90 or above years) with Alzheimer's disease, Cognitive impairment.

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


title: Single-cell RNA/ATAC multiomic analysis of bone marrow stromal cells of young bones [Prrx1cre_P21_multiome]

summary: A single nucleus transcriptomic and epigenomic profile of bone marrow stromal cells of the murine femur marked by Prrx1-cre at postnatal day 21 (P21)

overall_design: tdTomato+ cells were FACS-isolated from Prrx1-cre; R26R-tdTomato femur bone marrow at postnatal day 21 (P21). 15,000 nuclei were loaded onto 10X Genomics Chromium Single Cell Multiome ATAC + Gene Expression platform. Amplified DNA was sequenced by Illumina NovaSeq 6000


title: Single-cell ATACseq analysis of bone marrow stromal cells of young bones [Prrx1cre_P21_ATAC]

summary: A single cell chromatin accessibility profile of bone marrow stromal cells of the murine femur marked by Prrx1-cre at postnatal day 21 (P21)

overall_design: tdTomato+ cells were FACS-isolated from Prrx1-cre; R26R-tdTomato femur bone marrow at postnatal day 21 (P21). 30,000 single nuclei were loaded onto 10X Genomics Single Cell ATAC platform. Amplified DNA fragments were sequenced by Illumina NovaSeq 6000


title: Histone ChIP-seq from middle frontal area 46 (ENCSR135AYC)

summary:
H3K4me3 ChIP-seq on middle frontal area 46 tissue female adult (90 or above years) with Alzheimer's disease.

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


title: Histone ChIP-seq from middle frontal area 46 (ENCSR049KUR)


title: Single-cell RNAseq analysis of bone marrow stromal cells of old bones [Prrx1cre_18M_RNA]

summary: A single cell transcriptomic profile of bone marrow stromal cells of the murine femur marked by Prrx1-cre at 18 months of age (18M)

overall_design: tdTomato+ cells were FACS-isolated from Prrx1-cre; R26R-tdTomato femur bone marrow at 18 months of age (18M). 15,000 cells were loaded onto 10X Genomics Chromium Single Cell Expression Solution version 3 platform. cDNA was sequenced by Illumina NovaSeq 6000


title: A Growth Factor-Expressing Macrophage subpopulation orchestrates regenerative inflammation via GDF-15

status: Public on Oct 27 2021

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

overall_design: Refer to individual Series


title: Next Generation Sequencing Facilitates Quantitative Analysis of CD11C+/CD11C- CD8 T cells Transcriptomes

status: Public on Nov 01 2021

city: Jinan

first: An-Liang

last: Guo

address: No.44 West Wenhua Road

department: Department of Immunology

institute: School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University

summary: in order to understand the differences between CD11c+ CD8+ and CD11c- CD8+ T cells in human PBMCs, we isolated the two cell populations in three healthy donors and analyzed their gene expression profiles by RNAseq analyses.

overall_design: mRNA profiles of CD11C+CD8T and CD11C- CD8T from 3 healthy human donors


title: A Growth Factor-Expressing Macrophage subpopulation orchestrates regenerative inflammation via GDF-15 [scRNA-seq]

status: Public on Nov 03 2021

summary: Muscle regeneration is the result of the concerted action of multiple cell types driven by the temporarily controlled phenotype switches of infiltrating monocyte-derived macrophages. Proinflammatory macrophages transition into a phenotype that drives tissue repair through the production of effectors such as growth factors. This orchestrated sequence of regenerative inflammatory events, which we termed Regeneration-Promoting Program (RPP), is essential for proper repair. However, it is not well understood how specialized repair-macrophage identity develops in the RPP at the transcriptional level and how induced macrophage-derived factors coordinate tissue repair. Gene expression kinetics-based clustering of blood circulating Ly6Chigh, infiltrating inflammatory Ly6Chigh, and reparative Ly6Clow macrophages, isolated from injured muscle, identified the TGF-beta superfamily member, GDF-15, as a component of the RPP. Myeloid GDF-15 is required for proper muscle regeneration following acute sterile injury, as revealed by gain- and loss-of-function studies. Mechanistically, GDF-15 acts both on proliferating myoblasts and muscle-infiltrating myeloid cells. Epigenomic analyses of upstream regulators of Gdf15 expression identified that it is under the control of nuclear receptors RXR/PPARg. Finally, immune single-cell RNA-seq profiling revealed that Gdf15 is co-expressed with other known muscle regeneration-associated growth factors, and their expression is limited to a unique subpopulation of repair-type macrophages (Growth Factor-Expressing Macrophages, GFEM).

overall_design: Trancriptomic profiling of mouse CD45+ cells, after four days (D4) of CTX-induced acute sterile muscle injury using high throughput sequencing (scRNA-seq, 10x Chromium V3 chemistry).


title: Histone ChIP-seq from middle frontal area 46 (ENCSR016JFP)

summary:
H3K27me3 ChIP-seq on middle frontal area 46 tissue female adult (88 years) with Alzheimer's disease.

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


title: Genome-wide analysis of TERT-AD mouse cortical and hippocampal neurons upon Tert activation

status: Public on Oct 12 2021

first: Chang-Jiun

last: Wu

state: TX

address: 1515 Holcombe Blvd

department: Genomic Medicine

institute: University of Texas, MD Anderson Cancer Center

summary: Analysis of TERT-regulated global gene expression changes. The hypothesis tested in the present study was that neuronal TERT influences the regulation of gene expressions. Results provide important information of the response of in vivo mouse neurons to physiological TERT induction.

overall_design: Total RNA obtained from isolated Tert-activated adult mouse neurons in vivo compared to control neurons.

first: Ronald

middle: A

last: DePinho

first: Hong

last: Shim


title: Genome-wide CRISPR screen identifies cell cycle as a synthetic lethal pathway with SRSF2P95H mutation

status: Public on Sep 15 2021

city: Meblourne

first: Alistair

middle: Morgan

last: Chalk

state: VIC

address: 1G Royal Parade

department: Bioinformatics

institute: WEHI

summary: Current strategies to target RNA splicing mutant myeloid cancers propose disruption of normal splicing activity by targeting the splicing apparatus therapeutically. This approach is only modestly sensitizing and is also toxic to non-mutant bearing wild-type cells. To explore potentially exploitable genetic interactions with spliceosome mutations, we combined data mining and functional screening for synthetic lethal interactions with an Srsf2P95H/+ mutation. Analysis of mis-splicing events in a series of both human and murine SRSF2P95H mutant samples across multiple myeloid diseases (AML, MDS, CMML) was first performed to identify conserved mis-splicing events. From this analysis, we identified that the DNA repair and cell cycle pathways were overrepresented within the conserved mis-spliced transcript sets. In parallel, to functionally define pathways essential for survival and proliferation Srsf2P95H/+ cells, we performed a genome-wide pooled CRISPR loss of function screen using Hoxb8 immortalised R26-CreERki/+ Srsf2P95H/+ and R26-CreERki/+ Srsf2+/+ cell lines. We assessed for loss of sgRNA representation at three timepoints: immediately after Srsf2P95H/+ activation, and at one week and two weeks post Srsf2P95H/+ mutation. Pathway analysis demonstrated that the DNA damage response and cell cycle pathways were amongst the top synthetic lethal pathways with Srsf2P95H/+ mutation., Based on the loss of guide RNAs targeting Cdk6, we identified that Palbocilib, a CDK6 inhibitor, showed preferential sensitivity in Srsf2P95H/+ cell lines and in primary non-immortalised lin-cKIT+Sca-1+ cells compared to wild type controls. Our data strongly suggest that cell cycle and DNA damage response pathways are required for Srsf2P95H/+ cell survival, and that Palbociclib could be an alternative therapeutic option for targeting SRSF2 mutant myeloid cancers.

overall_design: Crispr screen using Hoxb8 imortalised GM-CSF cell line,  tamoxifen treated. 3 * R26-CreERT2 Srsf2+/+  (WT) vs 3 * R26-CreERT2 Srsf2P95H/+ (P95H). Each replicate was measured at 0, 4, 11 and 18 days post tamoxifen.

first: Jane

last: Xu

middle: M

first: Iva

last: Nikolic

first: Kaylene

last: Simpson

first: Monique

last: Smeets

first: Carl

last: Walkley


summary: Muscle regeneration is the result of the concerted action of multiple cell types driven by the temporarily controlled phenotype switches of infiltrating monocyte-derived macrophages. Proinflammatory macrophages transition into a phenotype that drives tissue repair through the production of effectors such as growth factors. This orchestrated sequence of regenerative inflammatory events, which we termed Regeneration-Promoting Program (RPP), is essential for proper repair. However, it is not well understood how specialized repair-macrophage identity develops in the RPP at the transcriptional level and how induced macrophage-derived factors coordinate tissue repair. Gene expression kinetics-based clustering of blood circulating Ly6Chigh, infiltrating inflammatory Ly6Chigh, and reparative Ly6Clow macrophages, isolated from injured muscle, identified the TGF-beta superfamily member, GDF-15, as a component of the RPP. Myeloid GDF-15 is required for proper muscle regeneration following acute sterile injury, as revealed by gain- and loss-of-function studies. Mechanistically, GDF-15 acts both on proliferating myoblasts and muscle-infiltrating myeloid cells. Epigenomic analyses of upstream regulators of Gdf15 expression identified that it is under the control of nuclear receptors RXR/PPARg. Finally, immune single-cell RNA-seq profiling revealed that Gdf15 is coexpressed with other known muscle regeneration-associated growth factors, and their expression is limited to a unique subpopulation of repair-type macrophages (Growth Factor-Expressing Macrophages, GFEM).

overall_design: Transcriptomic profiling of mouse Bone Marrow-Derived Macrophages (BMDM), from WT and RXRa/b KO mice using RNA-seq. Dataset contains 3 biological replicates per condition.

first: Wilhelm

middle: K

last: Berger


title: Epithelial memory of resolved inflammation limits tissue damage while promoting pancreatic tumorigenesis [scRNA-Seq]

status: Public on Sep 17 2021

city: Milan

first: Chiara

last: Balestrieri

address: Via Olgettina 58

department: Center for Omics Sciences

country: Italy

institute: IRCCS San Raffaele Scientific Institute

summary: Inflammation is a major risk factor for pancreatic ductal adenocarcinoma (PDAC). When occurring in the context of pancreatitis, mutations of KRAS accelerate tumor development. We discovered that long after its complete resolution, a transient inflammatory event primes pancreatic epithelial cells to subsequent transformation by oncogenic KRAS. Upon recovery from acute inflammation, epithelial cells of the pancreas display an enduring adaptive response associated with sustained transcriptional and epigenetic reprogramming. Such adaptation enables the prompt reactivation of acinar-to-ductal metaplasia (ADM) upon subsequent inflammatory events, thus efficiently limiting tissue damage via rapid decrease of zymogen production. We propose that since activating mutations of KRAS maintain an irreversible ADM, they may be beneficial and under strong positive selection in the context of recurrent pancreatitis.

overall_design: Pancreata were harvested from C57BL/6J wild-type mice at different time points before and after acute inflammation and digested  to obtain single cell suspension. Total RNA from each cell was processed for multiparallel sequencing.

first: E

last: Del Poggetto

first: I

last: Ho

first: S

last: Zhang

first: A

last: Viale


title: Transcriptome analysis of Hoxb8 imortalised GM-CSF cell lines with SRSF2 P95H mutation [RNA-seq]

overall_design: RNAseq of Hoxb8 imortalised GM-CSF cell line,  tamoxifen treated. 3 * R26-CreERT2 Srsf2+/+  (WT) vs 3 * R26-CreERT2 Srsf2P95H/+ (P95H) generated by deep sequencing, using Illumina NextSeq500.

middle: J


title: Analysis of Transcriptional Responses to Altitude-Induced Hypoxia in Bronchial Epithelium, Bronchio-Alveolar Cells, and Blood Reveals Differences Between Smokers and Nonsmokers [epithelial]

status: Public on Sep 14 2021

city: Oklahoma City

first: Susan

middle: Kasko

last: Munster

state: OK

address: 6500 S. MacArthur Blvd.

department: Office of Aerospace Medicine

institute: Federal Aviation Admininistration

summary: Blood, bronchial epithelium, and bronchio-alveolar cells were collected in a double blind study. Individuals were exposed to 'ground' and 'flight' conditions using a hypobaric chamber for approximately 5 hours. Blood samples were collected over 4 time points and both bronchial cells were collected at the last time point.

overall_design:
Samples were collected from 20 individuals, comprised of 10 smokers and 10 nonsmokers. Both subgroups of smokers and nonsmokers were comprised of 5 males and 5 females each.
Collection timepoint 4 = taken 1.5 hours after exposure to 'altitude' ended

first: Scott

last: Nicholson

first: Hilary

last: Uyhelji

first: David

middle: C

last: Hutchings

first: Vicky

middle: L

last: White

first: Dennis

last: Burian

first: Jordan

last: Metcalf


title: Single-cell RNAseq analysis of Gas1-creER-marked bone marrow stromal cells in young bones [Gas1CE;R26RtdT]

first: Noriaki

last: Ono

summary: A single cell transcriptomic profile of Gas1-creER-marked bone marrow stromal cells of the murine femur at postnatal day 23 (P23), pulsed at P21.

overall_design: tdTomato+ cells were FACS-isolated from Gas1-creER; R26R-tdTomato femur bone marrow at P23 (tamoxifen at P21). 15,000 cells were loaded onto 10X Genomics Chromium Single Cell Expression Solution version 3 platform. cDNA was sequenced by Illumina NovaSeq 6000


title: Single-cell RNAseq analysis of p53-deficient Fgfr3+ cell-derived bone marrow stromal cells [Fgfr3CE_p53-cKO]

summary: A single cell transcriptomic profile of p53-deficient bone marrow stromal cells of the murine femur at 4 months of age (4M), lineage-marked by Fgfr3-creER at postnatal day 21 (P21)

overall_design: tdTomato+ cells were FACS-isolated from Fgfr3-creER; Trp53(fl/fl); R26R-tdTomato (p53-cKO) femur bone marrow at 4 months of age (tamoxifen at P21). 15,000 cells were loaded onto 10X Genomics Chromium Single Cell Expression Solution version 3 platform. cDNA was sequenced by Illumina NovaSeq 6000


title: Endosteal stem cells in young bone marrow dictate active osteogenesis and aggressive tumorigenesis


title: Analysis of Transcriptional Responses to Altitude-Induced Hypoxia in Bronchial Epithelium, Bronchio-Alveolar Cells, and Blood Reveals Differences Between Smokers and Nonsmokers


title: Single-cell RNAseq analysis of Fgfr3+ cell-derived bone marrow stromal cells, p53 Control [Fgfr3CE_p53-cHet]

summary: A single cell transcriptomic profile of bone marrow stromal cells of the murine femur at 4 months of age (4M), lineage-marked by Fgfr3-creER at postnatal day 21 (P21), Control

overall_design: tdTomato+ cells were FACS-isolated from Fgfr3-creER; Trp53(fl/+); R26R-tdTomato (Control) femur bone marrow at 4 months of age (tamoxifen at P21). 15,000 cells were loaded onto 10X Genomics Chromium Single Cell Expression Solution version 3 platform. cDNA was sequenced by Illumina NovaSeq 6000


title: RNA-seq of murine lung mesenchymal stromal cells (LMSCs) during tumor development

status: Public on Sep 18 2021

city: suzhou

first: Zhiyuan

last: Zheng

address: 199,Ren ai Road

institute: Soochow University

summary:
Purpose: The goals of this study are to explore the function of  lung MSCs during tumor development
Methods: mRNA profiles of lung MSCs (murine) were generated by deep sequencing.

overall_design: RNA-seq of 3 different stge MSCs during tumor progress: adenoma/early pre-metastatic (E-LMSCs), early carcinoma/late pre-metastatic (L-LMSCs) and metastatic stage (M-LMSCs).n=2

first: Yufang

last: Shi


title: Single-cell RNAseq analysis of Fgfr3-creER-marked bone marrow stromal cells in young bones [Fgfr3CE;R26RtdT]

summary: A single cell transcriptomic profile of Fgfr3-creER-marked bone marrow stromal cells of the murine femur at postnatal day 23 (P23), pulsed at P21.

overall_design: tdTomato+ cells were FACS-isolated from Fgfr3-creER; R26R-tdTomato femur bone marrow at P23 (tamoxifen at P21). 15,000 cells were loaded onto 10X Genomics Chromium Single Cell Expression Solution version 3 platform. cDNA was sequenced by Illumina NovaSeq 6000


title: In vivo single-cell and bulk transcriptomics reveals murine Leishmania major infection drives a pro-inflammatory signature alongside a signature of decreased ribosomal biogenesis.

status: Public on Oct 08 2021

city: Little Rock

first: Ravi

middle: W.

last: Sun

state: Arkansas

address: 4301 W Markham St

department: Department of Otolaryngology - Head and Neck Surgery

institute: University of Arkansas for Medical Sciences

summary: Leishmania parasites cause cutaneous leishmanina (CL), a pathologic disease characterized by disfiguring, ulcerative skin lesions. Both parasite and host gene expression following infection with various Leishmania species has been investigated in vitro, but global transcriptional analysis following L. major infection in vivo is lacking. Thus, we conducted a comprehensive transcriptomic profiling study combining bulk RNA sequencing and single-cell RNA sequencing (scRNA-Seq) to identify global changes in gene expression in vivo following L. major infection. Bulk RNA-Seq analysis revealed that host immune response pathways like the antigen processing and presentation pathway were significantly enriched amongst differentially  expressed genes (DEGs) upon infection, while ribosomal pathways were significantly downregulated in infected mice compared to naive controls.  scRNA-Seq analyses revealed cellular heterogeneity including distince resident and recruitment cell types in the skin following L. major infection.  Within the individual immune cell types, several DEGs indicative of many interferon induced GTPases and antigen presentation molecules were significantly enhanced in the infected ears including macrophages (H2-K1, H2-D1, Gbp4, Gbp8, Gbp2), and inflammatory monocytes (Gbp2, Gbp5, Gbp7, Gbp3). Ingenuity Pathway Analysis of scRNA-Seq data indicated the antigen presentation pathway was increased with infection, while EIF2 signaling is the top downregulated pathway followed by eIF4/p70S6k and mTOR signaling in multiple cell types including macrophages, BECs, and LECs.  Altogether, this transcriptomic profile highlights known recruitment of myeloid cells to lesions and recognizes a previously undefined role for EIF2 signaling in murine L. major infection in vivo.

overall_design: Bulk RNA-Seq of naïve control ears compared to ear samples from 4 weeks post infection with Leishmania major promastigote parasites.

first: Gopinath

last: Venugopal

middle: T

last: Bird

first: Charity

last: Washam

first: Hayden

last: Roys

first: Anne

last: Bowlin

first: Stephanie

middle: D

last: Byrum

first: Tiffany

last: Weinkopff


title: Epithelial memory of resolved inflammation limits tissue damage while promoting pancreatic tumorigenesis

first: Chiara

last: Balestrieri


title: Analysis of Transcriptional Responses to Altitude-Induced Hypoxia in Bronchial Epithelium, Bronchio-Alveolar Cells, and Blood Reveals Differences Between Smokers and Nonsmokers [alveolar]

first: Susan

last: Munster

first: Scott

last: Nicholson

last: Uyhelji


title: Transcriptome analysis and genome-wide CRISPR screen of Hoxb8 imortalised GM-CSF cell lines

first: Alistair

last: Chalk


title: Next Generation Sequencing Facilitates Quantitative Analysis of E.coli, Wild Type and ΔrecA Transcriptomes

status: Public on Jul 06 2021

city: shenzhen

first: guan

last: yunpeng

address: 1088 Xueyuan Avenue, Nanshan District, Shenzhen, Guangdong Province

department: BME

institute: Southern University of Science and Technology

summary:
Purpose:Next-generation sequencing (NGS) has revolutionized systems-based analysis of cellular pathways. The goals of this study are to compare NGS-derived E.coli transcriptome profiling (RNA-seq) of Wild type and ΔrecA with or without antibiotics treatment.
Methods:libraries with different indices were multiplexed and loaded on an Illumina HiSeq instrument, Sequencing was carried out using a 2x150bp paired-end (PE) configuration, image analysis and base calling were conducted by the HiSeq Control Software (HCS) + OLB + GAPipeline-1.6 (Illumina) on the HiSeq instrument. Main data analysis include Quality Control(Cutadapt), Mapping(Bowtie2 (v2.2.6)),Expression analysis(HTSeq (v0.6.1p1)), Differential expression analysis (DESeq2 Bioconductor package).
Results:Using an optimized data analysis workflow, we mapped about 20 million sequence reads per sample to the E.coli genome, The treatment of ampicillin affected the transcriptomic profile of either in the wild type or the ΔrecA strain, compared with that of untreated control cells, with changes to the expression of 4373 and 4286 coding sequences, respectively. Analysis of only the genes with a log2 fold change (log2FC) of ≥ ± 2 showed that 161 and 248 genes were differentially expressed in the ampicillin-treated wild type and ΔrecA strains, respectively.
Conclusions:Our study represents the detailed analysis of E.coli transcriptomes, with biologic replicates, generated by RNA-seq technology. The optimized data analysis workflows reported here should provide a framework for comparative investigations of expression profiles. Our results show that NGS offers a comprehensive and more accurate quantitative and qualitative evaluation of mRNA content within a cell or tissue. We conclude that RNA-seq based transcriptome characterization would expedite genetic network analyses and permit the dissection of complex biologic functions.

overall_design: mRNA profiles of E.coli, wild type (WT) and ΔrecA with or without antibiotics treatment

first: Yunpeng

last: Guan

first: Leo

last: Zhang


title: Single-cell RNAseq analysis of bone marrow stromal cells of young bones [Prrx1cre_P21_RNA]

first: Noriaki

last: Ono

summary: A single cell transcriptomic profile of bone marrow stromal cells of the murine femur marked by Prrx1-cre at postnatal day 21 (P21)

overall_design: tdTomato+ cells were FACS-isolated from Prrx1-cre; R26R-tdTomato femur bone marrow at postnatal day 21 (P21). 15,000 cells were loaded onto 10X Genomics Chromium Single Cell Expression Solution version 3 platform. cDNA was sequenced by Illumina NovaSeq 6000


title: Telomerase Reverse Transcriptase Preserves Neuron Survival and Cognition in Alzheimer's Disease Models

first: Chang-Jiun

last: Wu

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

overall_design: Refer to individual Series