title: Cell cycle dynamics of chromosomal organisation at single-cell resolution

status: Public on Jul 06 2017

city: Cambridge

first: Steven

middle: William

last: Wingett

state: Cambs

address: Francis Crick Avenue, Cambridge Biomedical Campus

department: Cell Biology

institute: MRC Laboratory of Molecular Biology

summary: Chromosomes in proliferating metazoan cells undergo dramatic structural metamorphoses every cell cycle, alternating between a highly condensed mitotic structure facilitating chromosome segregation, and a decondensed interphase structure accommodating transcription, gene silencing and DNA replication. These cyclical structural transformations have been evident under the microscope for over a century, but their molecular-level analysis is still lacking. Here we use single-cell Hi-C to study chromosome conformations in thousands of individual cells, and discover a continuum of cis-interaction profiles that finely position individual cells along the cell cycle. We show that chromosomal compartments, topological domains (TADs), contact insulation and long-range loops, all defined by ensemble Hi-C maps, are governed by distinct cell cycle dynamics. In particular, DNA replication correlates with build-up of compartments and reduction in TAD insulation, while loops are generally stable from G1 through S and G2. Analysing whole genome 3D structural models using haploid cell data, we discover a radial architecture of chromosomal compartments with distinct epigenomic signatures. Our single-cell data creates an essential new paradigm for the re-interpretation of chromosome conformation maps through the prism of the cell cycle.

overall_design:
Hi-C: 45 samples analysed
Strand-specific nuclear RNA-seq: 4 samples analysed

first: Takashi

last: Nagano

first: Yaniv

last: Lubling

first: Csilla

last: Varnai

first: Carmel

last: Dudley

first: Wing

last: Leung

first: Yael

last: Baran

first: Netta

last: Mandelson-Cohen

first: Peter

last: Fraser

first: Amos

last: Tanay


title: Transcriptomes of peripheral blood mononuclear cells from a Guillain-Barre Syndrome patient and her healthy twin sampled at three different points of the disease evolution

status: Public on Sep 05 2015

city: Granada

first: Raquel

last: Tobes

state: Granada

address: Plaza Campo Verde 3 Atico

department: Bioinformatics

country: Spain

institute: Era7 Bioinformatics

type: Expression profiling by high throughput sequencing

summary: Guillain-Barré syndrome (GBS) is an immune-mediated peripheral neuropathy that debilitates the voluntary and autonomous response of the patient. In this study the transcriptome of peripheral blood mononuclear cells from a GBS patient and her healthy twin were compared to discover possible correlates of disease progression and recovery.

overall_design: Blood samples were collected simultaneously from the Guillain-Barré patient (A) and from her control healthy twin (B) at three different time points during disease progression from hospitalization in the intensive care unit (T1), passing to intermediate care (T2),  and at conclusion of locomotion rehabilitation program when the patient was close to abandon the hospital (T3).

first: José

last: de la Fuente

first: Ernesto

last: Doncel-Pérez

first: Lourdes

last: Mateos-Hernández

first: Eduardo

last: Pareja

first: Ángel

last: García-Forcada

first: Margarita

last: Villar

first: Francisco

last: Romero Ganuza

first: Virginia

last: Vila del Sol

first: Ricardo

last: Ramos

first: Isabel

middle: G

last: Fernández de Mera


title: Lin28b expression distinguishes fetal versus adult lymphopoiesis

status: Public on Feb 17 2012

city: Bethesda

first: Stefan

middle: Adi

last: Muljo

state: MD

address: 10 Center Drive

department: National Institute of Allergy and Infectious Diseases

country: USA

institute: National Institutes of Health

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

overall_design: Refer to individual Series


title: Gonadal Adipose Tissue Profiling In HMDP (high-fat/high-sucrose diet)

status: Public on Jan 08 2015

city: Los Angeles

first: Calvin

last: Pan

address: 675 Charles Young Dr South

institute: UCLA

summary: Identify genes in the gonadal adipose tissue whose expression is under genetic regulation in the Hybrid Mouse Diversity Panel (HMDP).  The HMDP comprises classical inbred and recombinant inbred wild type mice.  The RMA values of genes were used for genome wide association as described in Parks et al Cell Metabolism 2015.  These data are used to identify candidate genes at loci associated with obesity and dietary responsiveness.

overall_design: GWAS for expression of gonadal adipose tissue in inbred strains fed chow diet for 8 weeks followed by high-fat/high-sucrose diet 8 weeks

first: Aldons

middle: J

last: Lusis

first: Brian

last: Parks


title: Expression Profiling In HMDP (high-fat/high-sucrose diet)


title: microRNA profiling of fetal liver and adult bone marrow pro-B cells

summary: We used the NanoString mouse nCounter miRNA expression platform to compare the miRNA expression profiles of pro-B cells sorted from fetal liver and adult bone marrow in order to gain insight into changes in miRNA expression during B cell ontogeny.

overall_design: Fetal liver and adult bone marrow cells were harvested and FACS sorted for pro-B cells (B220+CD43+IgM-veCD19+CD24+). Total RNA was extracted and used for sample preparation and hybridization per manufacturer's instructions.

first: Joan

last: Yuan

middle: A


title: Identification of differential gene expression modulated by knockdown of MUC1 in MKN45 gastric carcinoma cells

status: Public on Nov 15 2011

city: Porto

first: Natalia

last: Costa

address: Rua Dr Roberto Frias s/n

country: Portugal

institute: IPATIMUP

summary: Transcripts upregulated or downregulated by knockdown of MUC1 were identified through expression profiling of a total of 12,135 genes in comparison with MKN45- MUC1 RNAi clones and control clones.

overall_design: We endeavored to identify genes which expression is affected by MUC1 by performing cDNA microarray analysis on two MKN45 MUC1 RNAi clones and one control clone.

first: David

middle: L

last: Kelly

first: Natália


title: Genetic complexity in yeast transcripts

status: Public on Jan 20 2005

city: Berkeley

first: Rachel

middle: B

last: Brem

state: CA

address: 321 Koshland Hall

department: Plant and Microbial Biology

institute: UC Berkeley

summary:
Haploid segregants from a cross between the yeast strains BY4716 and RM11-1a as in Brem et al. 2002 and Yvert et al. 2003.  This series contains all GSE617 samples (re-submitted for convenience), plus 27 additional segregants assayed with the same protocol and the same reference sample as GSE617.
Keywords: other


title: Polygenic and directional regulatory evolution across pathways in Saccharomyces

status: Public on Feb 22 2010

summary: We assess the prevalence of polygenic evolution in pathways between the yeasts S. cerevisiae and S. bayanus.  We first established short-read sequencing methods to detect cis-regulatory variation in a diploid hybrid between the species.  We then formulated an analytic strategy to test for the scenario in which selective pressure in one species, to increase or decrease the activity of a pathway, has driven the accumulation of cis-regulatory variants that act in the same direction on gene expression.  Application of this test revealed a variety of yeast pathways with evidence for directional regulatory evolution.

sample_organism: Saccharomyces bayanus x Saccharomyces cerevisiae

overall_design: Measurement of allele-specific expression of each ortholog in a diploid hybrid between Saccharomyces species

first: James

middle: H

last: Bullard


title: Single-cell RNA-seq of melanoma ecosystems reveals sources of T cells exclusion linked to immunotherapy clinical outcomes

status: Public on Nov 01 2018

first: Orr

last: Ashenberg

state: MA

address: 415 Main Street

department: Klarman Cell Observatory

institute: Broad Institute

summary: Immune checkpoint inhibitors (ICI) produce durable responses in some melanoma patients, but many patients derive no clinical benefit, and the molecular underpinnings of such resistance remain elusive. Here, we leveraged single-cell RNA-seq (scRNA-seq) from 31 melanoma tumors and novel computational methods to interrogate malignant cell states that promote immune evasion. We identified a resistance program expressed by malignant cells that is associated with T cell exclusion and immune evasion. The program is present prior to immunotherapy, characterizes cold niches, and predicts clinical responses to anti-PD-1 therapy in an independent cohort of 112 melanoma patients. CDK4/6-inhibition represses this program in individual malignant cells, induces senescence, and reduces melanoma tumor outgrowth in a mouse model when given in combination with immunotherapy. Our study provides a high-resolution landscape of ICI resistant cell states, identifies clinically predictive signatures, and forms a basis for the development of novel therapeutic strategies that could overcome immunotherapy resistance.

overall_design:
Individual cells were dissociated from fresh tumor resections, isolated immune and non-immune cells by FACS based on CD45 staining, and profiled with a modified full length SMART-Seq2 protocol.

** Submitter declares that the raw reads will be made available through dbGaP. **

first: Livnat

last: Jerby-Arnon

first: Parin

last: Shah

first: Michael

middle: S

last: Cuoco

first: Christopher

last: Rodman

first: Mei

last: Su

first: Johannes

middle: C

last: Melms

last: Leeson

first: Abhay

last: Kanodia

first: Shaolin

last: Mei

first: Jia

middle: R

last: Lin

first: Shu

last: Wang

first: Bokang

last: Rabasha

last: Liu

first: Gao

last: Zhang

first: Claire

last: Margolais

first: Patrick

last: Ott

first: Elizabeth

middle: I

last: Buchbinder

first: Riz

last: Haq

first: F

last: Hodi

first: G

middle: M

last: Boland

first: Ryan

last: Sullivan

first: Dennie

middle: T

last: Frederick

first: Benchun

last: Miao

first: Tabea

last: Moll

first: Keith

last: Flaherty

first: Meenhard

last: Herlyn

first: Russell

middle: W

last: Jenkins

first: Rohit

last: Thummalapalli

first: Monika

last: Kowalczyk

first: Israel

last: Cañadas

first: Bastian

last: Schilling

first: Adam

middle: N

last: Cartwright

first: Adrienne

last: Luoma

first: Shruti

last: Malu

last: Hwu

first: Chantale

last: Bernatchez

first: Marie


title: BYxwild_40

status: Public on May 01 2002

first: Rachel

last: Brem

summary:
Expression analysis of F1 haploid segregants from a cross between BY4716 (isogenic to S288c) and a wild isolate collected by R. Mortimer.  Each segregant sample was subjected to a dye-swap pair of arrays.  All arrays used the same pool of reference BY4716 sample.  In sample titles, "BY" alone signifies the reference sample and all other strings represent segregants.  All sample titles are of the form S1-S2.  S1 indicates the sample whose signal was read as channel 1 (Cy5 labeling, fluorescence at 635 nm) and S2 as channel 2 (Cy3, 532 nm).
Keywords: repeat sample

first: Gael

last: Yvert

first: Rebecca

last: Clinton

first: Leonid

last: Kruglyak


title: BY_wild_parents

summary:
Expression analysis of BY4716(isogenic to S288c) and a wild isolate collected by R. Mortimer.  Each strain was grown in culture 6 independent times and RNA from each culture was isolated.  Each of these RNA samples was subjected to a dye-swap pair of arrays (except the "RM11" sample, which only got one array).  All arrays used the same pool of reference BY4716 sample.  In sample titles, "BY" alone signifies the reference sample and all other strings represent independent cultures.  All sample titles are of the form S1-S2.  S1 indicates the sample whose signal was read as channel 1 (Cy5 labeling, fluorescence at 635 nm) and S2 as channel 2 (Cy3, 532 nm).
Keywords: repeat sample


title: Expression of human aortic endothelial cells treated with or without oxidized phospholipids (II)

status: Public on Jul 20 2011

city: La Jolla

first: Casey

last: Romanoski

address: 9500 Gliman Dr.

institute: UCSD

summary:
Oxidized phospoholipids are a pro-inflammatory component of minimally modified lipoproteins that get trapped in the subendothelial space of atherosclerotic plaques of large arteries. To model the response of endothelial cells in a pro-atherosclerotic enviroment we measured the expression in primary endothelial cells with and without treatment with oxidized phsopolipids from 96 genetically identical donors of anonymous origin.
These samples are an extention of samples of similar origin deposited in GSE20060

overall_design:
Primary human aortic endothelial cells were collected from aortic heart explants of heart transplant donors and cultured in standard cell culture condiditions. At confluence, cells were treated with or without  40 ug/ml oxidized 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphatidylcholine (Ox-PAPC) for 4 hours in media 199 containing 1% fetal bovine serum. After 4 hours, the cells were collected for RNA extraction and quantification of transcripts via microarrays.

Application of electronic probe mask (HT_U133Amsk.cdf) on raw data.

middle: E

first: AJ

last: Lusis


title: Serum stimulation of fibroblasts with cycloheximide

status: Public on Jun 27 2002

city: Stanford

last: Stanford Microarray Database

address: 300 Pasteur Drive

department: Stanford University, School of Medicine

institute: Stanford Microarray Database (SMD)

summary:
The transcriptional program in the response of human fibroblasts to serum. Serum was added to fibroblasts in the presence of cycloheximide.
This study is described more fully in Iyer VR, et al. 1999. Science 283:83-7
Keywords: time-course

first: V

last: Iyer

first: M

last: Eisen

first: D

last: Ross

first: G

last: Schuler

first: T

last: Moore

first: J

last: Lee

last: Trent

first: L

last: Staudt

last: Hudson

last: Boguski

last: Lashkari

last: Shalon

last: Botstein

first: P

middle: O

last: Brown


title: Single-cell Hi-C reveals unique chromatin reorganization at oocyte-to-zygote transition

status: Public on Mar 23 2017

city: Basel

first: Ilya

middle: M.

last: Flyamer

address: Maulbeerstrasse 66

country: Switzerland

institute: Friedrich Miescher Institute for Biomedical Research

summary: Chromatin is reorganized and reprogrammed after fertilization to produce a totipotent zygote with the potential to generate a new organism. In mammals, the maternal genome inherited through the oocyte and the paternal genome provided by sperm coexist as separate haploid nuclei in interphase of the first cell cycle. How these two epigenetically distinct genomes are spatially organized remains poorly understood. Existing chromosome conformation capture-based methods are inapplicable to oocytes and zygotes due to paucity of material. To study the three-dimensional organization of chromatin in rare cell types, we developed a simplified single-cell Hi-C (sscHi-C) protocol that provides 100-fold more contacts per cell than a previous method. Using sscHi-C, we show that chromatin architecture is uniquely reorganized during the oocyte-to-zygote transition. We found that major features of chromosome organization, compartments, domains and loops are all present in individual cells, with noticeable cell-to-cell variation and differences between male and female nuclei in zygotes. Compartments detected in male nuclei are notably absent from female nuclei, indicating these are the first mammalian interphase nuclei lacking this higher-order structure. While compartments in single cells closely resemble compartments from the cell population, TADs manifest themselves as contact domains (CDs) that differ from cell to cell, nevertheless averaging into TADs in pooled data. Finally, scaling of contact probability with genomic separations suggests that chromosome conformations in oocyte and zygote nuclei are fundamentally different and each are distinct from the global organization of chromosomes in other interphase cells. We conclude that chromatin organization of zygote nuclei is unique and can serve as the chromatin "ground state" of a totipotent cell.

sample_organism:
Homo sapiens
Mus musculus

platform_organism:
Homo sapiens
Mus musculus

overall_design: We generated 98 HiC libraries from single oocytes (includes comparison of NSN and SN oocytes + two different experimental conditions), 82 libraries from nuclei of zygotes (comparison of maternal vs paternal nuclei + 2 experimental conditions), 2 libraries of bulk K562 cells compared to 34 libraries of single K562 cells and 2 libraries of bulk MEL cells (with 2 different fixation conditions).

first: Johanna

last: Gassler

first: Maxim

last: Imakaev

first: Hugo

last: Brandao

first: Sergey

middle: V

last: Ulianov

first: Nezar

last: Abdennur

last: Razin

last: Mirny

first: Kikue

last: Tachibana-Konwalski


title: Single cell transcriptome from aplastic anemia (AA) and healthy donors [3' RNA-seq]

status: Public on Mar 31 2021

city: Tianjin

first: Caiying

last: Zhu

address: Heping District, Nanjing Road, 288

country: China

institute: Institute of Hematology and Blood Disease Hospital

summary: Transcriptome analysis of hematopoietic stem and progenitor cells (HSPCs) and T cells collected from bone marrow and peripheral blood of healthy donors and aplastic anemia patients untreated or response to immunosuppressive therapy.

overall_design: 3' end mRNA profiles of hematopoietic stem and progenitor cells (HSPCs) and T cells under aplastic anemia (AA) and healthy conditions were generated by deep sequencing at single cell resolution, using Illumina Hiseq

first: Chenchen

last: Wang

first: Yu

last: Lian

first: Peng

last: Wu

first: Xuan

last: Li

first: Jun

last: Shi

first: Ping

first: Tao

last: Cheng