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GSE70685

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Musashi-2 attenuates AHR signalling to expand human haematopoietic stem cells

Organism: Homo sapiens
Platform: GPL11154
Samples: 8
Experiment Types:
Expression profiling by high throughput sequencing
Submitted: Jul 09 2015
Last Updated: May 15 2019
Status: Public on Apr 27 2016
Contact: Brian,,Wilhelm (University of Montreal)

Relations

BioProject: https://www.ncbi.nlm.nih.gov/bioproject/PRJNA289354 SRA: https://www.ncbi.nlm.nih.gov/sra?term=SRP060605

Summary

A greater understanding of the molecular pathways that underpin the unique human hematopoietic stem and progenitor cell (HSPC) self-renewal program will improve strategies to expand these critical cell types for regenerative therapies. The post-transcriptional mechanisms guiding HSPC fate during ex vivo expansion have not been closely investigated. Using shRNA-mediated knockdown, we show that the RNA-binding protein (RBP) Musashi-2 (MSI2) is required for human HSPC self-renewal. Conversely, when overexpressed, MSI2 induces multiple pro-self-renewal phenotypes, including significant ex vivo expansion of short- and long-term repopulating cells through direct attenuation of aryl hydrocarbon receptor (AHR) signaling. Using a global analysis of MSI2-RNA interactions, we determined that MSI2 post-transcriptionally downregulates canonical AHR pathway components in cord blood HSPCs. Our study provides new mechanistic insight into RBP-controlled RNA networks that underlie the self-renewal process and provides evidence that manipulating such networks can provide a novel means to enhance the regenerative potential of human HSPCs expanded ex vivo.

Overall Design

4 samples were used for RNA-seq (4 biological duplicate) including 2 sets of control samples (irrelvant shRNA kncok-downs)

Analysis (3 steps)

View Data Processing
Processing steps for GSE70685
  1. Reads for all samples were mapped to the human genome using Casava (Ver 1.8.2) with default paramters
  2. RPKM values and reads counts were calculated using Casava
  3. Analysis of differntial gene expression was performed thorugh ratio analysis and R (Deseq package)

Supplementary Files (2)

GSE70685_KH_DESeq_results.xlsx Download
GSE70685_KH_ratios_results.xlsx Download
GEO Samples (8)
GSM1816429 GSM1816430 GSM1816431 GSM1816432 GSM1816433 GSM1816434 GSM1816435 GSM1816436

Dataset Citations (1)

Musashi-2 attenuates AHR signalling to expand human haematopoietic stem cells.
PMID 27121842 · 2016 · Nature
Stefan Rentas, Nicholas Holzapfel, Muluken S Belew, Gabriel Pratt, Veronique Voisin, Brian T Wilhelm, Gary D Bader, Gene W Yeo, Kristin J Hope

SRA Experiments (8) and Runs (24)

Total: 48502 MB
SRX1090960 SRP060605 RNA-Seq PAIRED
GSM1816429: MSI2 over expression samples - expt 1; Homo sapiens; RNA-Seq
Sample: SRS986647
BioProject: PRJNA289354
BioSample: SAMN03853075
Platform: ILLUMINA
Instrument: Illumina HiSeq 2000
Organism: Homo sapiens
Sample attributes
source_name: Cord blood stem cells
treatment: MSI2 over-expression
cell type: Cord blood stem cells
Original files (1)
Cord blood stem cells
Runs (3)
Run Spots Bases Size (MB) Files Link
SRR2095416 15387577 3077515400 1848.7 MA_MSI2_248_C349KACXX_L005_R1.fastq.gz, MA_MSI2_248_C349KACXX_L005_R2… SRA
SRR2095417 17938984 3587796800 2227.31 MA_MSI2_248_C349KACXX_L006_R1.fastq.gz, MA_MSI2_248_C349KACXX_L006_R2… SRA
SRR2095418 15395135 3079027000 1858.7 MA_MSI2_248_C349KACXX_L007_R1.fastq.gz, MA_MSI2_248_C349KACXX_L007_R2… SRA
SRX1090961 SRP060605 RNA-Seq PAIRED
GSM1816430: MSI2 over expression samples - expt 2; Homo sapiens; RNA-Seq
Sample: SRS986646
BioProject: PRJNA289354
BioSample: SAMN03853076
Platform: ILLUMINA
Instrument: Illumina HiSeq 2000
Organism: Homo sapiens
Sample attributes
source_name: Cord blood stem cells
treatment: MSI2 over-expression
cell type: Cord blood stem cells
Original files (1)
Cord blood stem cells
Runs (3)
Run Spots Bases Size (MB) Files Link
SRR2095419 16016412 3203282400 1919.09 MA_MSI2_254_C349KACXX_L005_R1.fastq.gz, MA_MSI2_254_C349KACXX_L005_R2… SRA
SRR2095420 18800741 3760148200 2328.69 MA_MSI2_254_C349KACXX_L006_R1.fastq.gz, MA_MSI2_254_C349KACXX_L006_R2… SRA
SRR2095421 16013111 3202622200 1928.25 MA_MSI2_254_C349KACXX_L007_R1.fastq.gz, MA_MSI2_254_C349KACXX_L007_R2… SRA
SRX1090962 SRP060605 RNA-Seq PAIRED
GSM1816431: MSI2 over expression control - expt 1; Homo sapiens; RNA-Seq
Sample: SRS986640
BioProject: PRJNA289354
BioSample: SAMN03853077
Platform: ILLUMINA
Instrument: Illumina HiSeq 2000
Organism: Homo sapiens
Sample attributes
source_name: Cord blood stem cells
treatment: control
cell type: Cord blood stem cells
Original files (1)
Cord blood stem cells
Runs (3)
Run Spots Bases Size (MB) Files Link
SRR2095422 15312895 3062579000 1835.62 MA_248_C349KACXX_L005_R1.fastq.gz, MA_248_C349KACXX_L005_R2.fastq.gz,… SRA
SRR2095423 17935800 3587160000 2220.18 MA_248_C349KACXX_L006_R1.fastq.gz, MA_248_C349KACXX_L006_R2.fastq.gz,… SRA
SRR2095424 15311035 3062207000 1843.79 MA_248_C349KACXX_L007_R1.fastq.gz, MA_248_C349KACXX_L007_R2.fastq.gz,… SRA
SRX1090963 SRP060605 RNA-Seq PAIRED
GSM1816432: MSI2 over expression control - expt 2; Homo sapiens; RNA-Seq
Sample: SRS986639
BioProject: PRJNA289354
BioSample: SAMN03853078
Platform: ILLUMINA
Instrument: Illumina HiSeq 2000
Organism: Homo sapiens
Sample attributes
source_name: Cord blood stem cells
treatment: control
cell type: Cord blood stem cells
Original files (1)
Cord blood stem cells
Runs (3)
Run Spots Bases Size (MB) Files Link
SRR2095425 16425842 3285168400 1968.93 MA_254_C349KACXX_L005_R1.fastq.gz, MA_254_C349KACXX_L005_R2.fastq.gz,… SRA
SRR2095426 19530145 3906029000 2417.25 MA_254_C349KACXX_L006_R1.fastq.gz, MA_254_C349KACXX_L006_R2.fastq.gz,… SRA
SRR2095427 16440130 3288026000 1980.28 MA_254_C349KACXX_L007_R1.fastq.gz, MA_254_C349KACXX_L007_R2.fastq.gz,… SRA
SRX1090964 SRP060605 RNA-Seq PAIRED
GSM1816433: MSI2 shRNA knock down - expt 1; Homo sapiens; RNA-Seq
Sample: SRS986638
BioProject: PRJNA289354
BioSample: SAMN03853079
Platform: ILLUMINA
Instrument: Illumina HiSeq 2000
Organism: Homo sapiens
Sample attributes
source_name: Cord blood stem cells
treatment: MSI2 knockdown
cell type: Cord blood stem cells
Original files (1)
Cord blood stem cells
Runs (3)
Run Spots Bases Size (MB) Files Link
SRR2095428 15581175 3116235000 1876.11 sh332_248_C349KACXX_L005_R1.fastq.gz, sh332_248_C349KACXX_L005_R2.fas… SRA
SRR2095429 18154278 3630855600 2259.04 sh332_248_C349KACXX_L006_R1.fastq.gz, sh332_248_C349KACXX_L006_R2.fas… SRA
SRR2095430 15595871 3119174200 1887.6 sh332_248_C349KACXX_L007_R1.fastq.gz, sh332_248_C349KACXX_L007_R2.fas… SRA
SRX1090965 SRP060605 RNA-Seq PAIRED
GSM1816434: MSI2 shRNA knock down - expt 2; Homo sapiens; RNA-Seq
Sample: SRS986637
BioProject: PRJNA289354
BioSample: SAMN03853080
Platform: ILLUMINA
Instrument: Illumina HiSeq 2000
Organism: Homo sapiens
Sample attributes
source_name: Cord blood stem cells
treatment: MSI2 knockdown
cell type: Cord blood stem cells
Original files (1)
Cord blood stem cells
Runs (3)
Run Spots Bases Size (MB) Files Link
SRR2095431 15888489 3177697800 1908.32 sh332_254_C349KACXX_L005_R1.fastq.gz, sh332_254_C349KACXX_L005_R2.fas… SRA
SRR2095432 18610472 3722094400 2309.46 sh332_254_C349KACXX_L006_R1.fastq.gz, sh332_254_C349KACXX_L006_R2.fas… SRA
SRR2095433 15919469 3183893800 1921.32 sh332_254_C349KACXX_L007_R1.fastq.gz, sh332_254_C349KACXX_L007_R2.fas… SRA
SRX1090966 SRP060605 RNA-Seq PAIRED
GSM1816435: MSI2 shRNA knock down - control 1; Homo sapiens; RNA-Seq
Sample: SRS986636
BioProject: PRJNA289354
BioSample: SAMN03853081
Platform: ILLUMINA
Instrument: Illumina HiSeq 2000
Organism: Homo sapiens
Sample attributes
source_name: Cord blood stem cells
treatment: control
cell type: Cord blood stem cells
Original files (1)
Cord blood stem cells
Runs (3)
Run Spots Bases Size (MB) Files Link
SRR2095434 15920071 3184014200 1901.87 shRFP_248_C349KACXX_L005_R1.fastq.gz, shRFP_248_C349KACXX_L005_R2.fas… SRA
SRR2095435 18658426 3731685200 2304.18 shRFP_248_C349KACXX_L006_R1.fastq.gz, shRFP_248_C349KACXX_L006_R2.fas… SRA
SRR2095436 15918622 3183724400 1910.48 shRFP_248_C349KACXX_L007_R1.fastq.gz, shRFP_248_C349KACXX_L007_R2.fas… SRA
SRX1090967 SRP060605 RNA-Seq PAIRED
GSM1816436: MSI2 shRNA knock down - control 2; Homo sapiens; RNA-Seq
Sample: SRS986635
BioProject: PRJNA289354
BioSample: SAMN03853082
Platform: ILLUMINA
Instrument: Illumina HiSeq 2000
Organism: Homo sapiens
Sample attributes
source_name: Cord blood stem cells
treatment: control
cell type: Cord blood stem cells
Original files (1)
Cord blood stem cells
Runs (3)
Run Spots Bases Size (MB) Files Link
SRR2095437 15124783 3024956600 1822.21 shRFP_254_C349KACXX_L005_R1.fastq.gz, shRFP_254_C349KACXX_L005_R2.fas… SRA
SRR2095438 17563048 3512609600 2187.48 shRFP_254_C349KACXX_L006_R1.fastq.gz, shRFP_254_C349KACXX_L006_R2.fas… SRA
SRR2095439 15169759 3033951800 1836.68 shRFP_254_C349KACXX_L007_R1.fastq.gz, shRFP_254_C349KACXX_L007_R2.fas… SRA

Linked Publications (1)

Musashi-2 attenuates AHR signalling to expand human haematopoietic stem cells.
Nature · 2016

Data Files (31)

Accession File Name Stored Type Output Type Mapping Assembly Size Download
— MA_248_C349KACXX_L005_R1.fastq.gz RNA-Seq 1.8 GB link
— MA_248_C349KACXX_L005_R2.fastq.gz RNA-Seq 1.8 GB link
— MA_248_C349KACXX_L006_R1.fastq.gz RNA-Seq 2.2 GB link
— MA_248_C349KACXX_L007_R1.fastq.gz RNA-Seq 1.8 GB link
— MA_254_C349KACXX_L005_R1.fastq.gz RNA-Seq 1.9 GB link
— MA_254_C349KACXX_L006_R1.fastq.gz RNA-Seq 2.4 GB link
— MA_254_C349KACXX_L007_R1.fastq.gz RNA-Seq 1.9 GB link
— MA_MSI2_248_C349KACXX_L005_R1.fastq.gz RNA-Seq 1.8 GB link
— MA_MSI2_248_C349KACXX_L006_R1.fastq.gz RNA-Seq 2.2 GB link
— MA_MSI2_248_C349KACXX_L006_R2.fastq.gz RNA-Seq 2.2 GB link
— MA_MSI2_248_C349KACXX_L007_R1.fastq.gz RNA-Seq 1.8 GB link
— MA_MSI2_254_C349KACXX_L005_R1.fastq.gz RNA-Seq 1.9 GB link
— MA_MSI2_254_C349KACXX_L006_R1.fastq.gz RNA-Seq 2.3 GB link
— MA_MSI2_254_C349KACXX_L007_R1.fastq.gz RNA-Seq 1.9 GB link
— MA_MSI2_254_C349KACXX_L007_R2.fastq.gz RNA-Seq 1.9 GB link
— sh332_248_C349KACXX_L005_R1.fastq.gz RNA-Seq 1.8 GB link
— sh332_248_C349KACXX_L006_R1.fastq.gz RNA-Seq 2.2 GB link
— sh332_248_C349KACXX_L007_R1.fastq.gz RNA-Seq 1.8 GB link
— sh332_254_C349KACXX_L005_R1.fastq.gz RNA-Seq 1.9 GB link
— sh332_254_C349KACXX_L006_R1.fastq.gz RNA-Seq 2.3 GB link
— sh332_254_C349KACXX_L007_R1.fastq.gz RNA-Seq 1.9 GB link
— sh332_254_C349KACXX_L007_R2.fastq.gz RNA-Seq 1.9 GB link
— shRFP_248_C349KACXX_L005_R1.fastq.gz RNA-Seq 1.9 GB link
— shRFP_248_C349KACXX_L006_R1.fastq.gz RNA-Seq 2.3 GB link
— shRFP_248_C349KACXX_L007_R1.fastq.gz RNA-Seq 1.9 GB link
— shRFP_254_C349KACXX_L005_R1.fastq.gz RNA-Seq 1.8 GB link
— shRFP_254_C349KACXX_L006_R1.fastq.gz RNA-Seq 2.1 GB link
— shRFP_254_C349KACXX_L007_R1.fastq.gz RNA-Seq 1.8 GB link
— SRR2095420 RNA-Seq 2.3 GB link
— SRR2095423 RNA-Seq 2.2 GB link
— SRR2095432 RNA-Seq 2.3 GB link