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GSE180129

GSE GEO
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Global Identification of the miR-130a targetome in human HSPC Reveals a Novel Role for TBL1XR1 in Hematopoietic Stem Cell Self-Renewal and t(8;21) AML

Organism: Homo sapiens
Platform: GPL24676
Samples: 9
Experiment Types:
Other
Submitted: Jul 14 2021
Last Updated: Jul 01 2024
Status: Public on Mar 08 2022
Contact: Gene,,Yeo (UCSD)

Relations

SubSeries of: GSE181140 BioProject: https://www.ncbi.nlm.nih.gov/bioproject/PRJNA746604 SRA: https://www.ncbi.nlm.nih.gov/sra?term=SRP328366

Summary

Gene expression profiling and proteome analysis of normal and malignant hematopoietic stem cells (HSC) point to shared core stemness properties. However, discordance between mRNA and protein signatures underscores an important role for post-transcriptional regulation by miRNAs in governing this critical nexus. Here, we identify miR-130a as a regulator of HSC self-renewal and differentiation. Integration of protein mass spectrometry and chimeric AGO2 eCLIP-seq identify TBL1XR1 as a primary miR-130a target. TBL1XR1 loss of function phenocopies miR-130a enforced expression impairing lymphoid differentiation and expanding long-term (LT)-HSC. This post-transcriptional regulation by miR-130a is usurped in t(8;21) acute myeloid leukemia (AML), whereby reduction of miR-130a results in differentiation of leukemic cells by altering chromatin binding and composition of the AML1-ETO complex. Our study establishes that comprehensive identification of the miRNA targetome within primary cells enables discovery of novel genes and molecular networks underpinning stemness properties of normal and leukemic cells.

Overall Design

Identification of miR-130a targets using transcriptome-wide chimeric AGO2 eCLIP-seq and miR-130a targeted chimeric AGO2 eCLIP-seq in CD34+ hematopoietic stem and progenitor cells (HSPC) and Kasumi-1 AML cell line

Analysis (24 steps)

View Data Processing
Processing steps for GSE180129
  1. Sequenced reads were reformatted to include randomers in read headers with umi_tools (1.0.0).
  2. Args: --random-seed 1 --bc-pattern NNNNNNNNNN
  3. Reads were then trimmed with cutadapt (1.14).
  4. Args: --match-read-wildcards -O 1 --times 1 -e 0.1 --quality-cutoff 6 -m 18 -a InvRNA*.fasta (fasta sequences can be found at: https://github.com/YeoLab/eclip/tree/master/example/inputs/)
  5. Reads were then trimmed again with cutadapt (1.14) to remove double-ligation events.
  6. Args: --match-read-wildcards -O 5 --times 1 -e 0.1 --quality-cutoff 6 -m 18 -a Ril19.fasta (fasta sequences can be found at: https://github.com/YeoLab/eclip/tree/master/example/inputs/)
  7. For targeted miR-130a datasets, reads that did not contain the primer sequence (CAGUGCAAUGUUAAAAGGGCAU) were filtered out.
  8. For total chimeric eCLIP datasets, 10nt from the 3'end of Read1 was trimmed with umi_tools.
Showing first 8 steps.

Supplementary Files (2)

GSE180129_RAW.tar Download
GSE180129_cellsB_rep1.vs.cellsB_rep2.bed.gz Download
GEO Samples (9)

Dataset Citations (1)

Identification of the global miR-130a targetome reveals a role for TBL1XR1 in hematopoietic stem cell self-renewal and t(8;21) AML.
PMID 35263585 · 2022 · Cell reports
Gabriela Krivdova, Veronique Voisin, Erwin M Schoof, Sajid A Marhon, Alex Murison, Jessica L McLeod, Martino M Gabra, Andy G X Zeng, Stefan Aigner, Brian A Yee, Alexander A Shishkin, Eric L Van Nostrand, Karin G Hermans, Aaron C Trotman-Grant, Nathan Mbong, James A Kennedy, Olga I Gan, Elvin Wagenblast, Daniel D De Carvalho, Leonardo Salmena, Mark D Minden, Gary D Bader, Gene W Yeo, John E Dick, Eric R Lechman

SRA Experiments (9) and Runs (9)

Total: 16685 MB
SRX11449739 SRP328366 RIP-Seq PAIRED
GSM5453665: cells B total chimeric eCLIP, rep 1; Homo sapiens; RIP-Seq
Sample: SRS9489969
BioProject: PRJNA746604
BioSample: SAMN20222622
Platform: ILLUMINA
Instrument: Illumina NovaSeq 6000
Organism: Homo sapiens
Sample attributes
source_name: CD34+ cord blood
tissue: CD34+ cord blood
cell type: Lineage-depleted human cord blood cells sorted to collect CD34+ CB cells
rip antibody: AGO2 clone 4F9 (Santa Cruz, sc-53521)
inline barcode1: Ril19
Original files (1)
CD34+ cord blood
Runs (1)
Run Spots Bases Size (MB) Files Link
SRR15142308 36085496 7289270192 2208.71 Au2_S2_L001_R1_001.fastq.gz, Au2_S2_L001_R2_001.fastq.gz, SRR15142308… SRA
SRX11449740 SRP328366 RIP-Seq PAIRED
GSM5453666: cells B total chimeric eCLIP, rep 2; Homo sapiens; RIP-Seq
Sample: SRS9489970
BioProject: PRJNA746604
BioSample: SAMN20222621
Platform: ILLUMINA
Instrument: Illumina NovaSeq 6000
Organism: Homo sapiens
Sample attributes
source_name: CD34+ cord blood
tissue: CD34+ cord blood
cell type: Lineage-depleted human cord blood cells sorted to collect CD34+ CB cells
rip antibody: AGO2 clone 4F9 (Santa Cruz, sc-53521)
inline barcode1: Ril19
Original files (1)
CD34+ cord blood
Runs (1)
Run Spots Bases Size (MB) Files Link
SRR15142309 32429965 6550852930 2017.52 Au3_S3_L001_R1_001.fastq.gz, Au3_S3_L001_R2_001.fastq.gz, SRR15142309… SRA
SRX11449741 SRP328366 RIP-Seq PAIRED
GSM5453667: cells B total chimeric eCLIP size-matched input, rep 1; Homo sapiens; RIP-Seq
Sample: SRS9489971
BioProject: PRJNA746604
BioSample: SAMN20222620
Platform: ILLUMINA
Instrument: Illumina NovaSeq 6000
Organism: Homo sapiens
Sample attributes
source_name: CD34+ cord blood
tissue: CD34+ cord blood
cell type: Lineage-depleted human cord blood cells sorted to collect CD34+ CB cells
rip antibody: none
inline barcode1: Ril19
Original files (1)
CD34+ cord blood
Runs (1)
Run Spots Bases Size (MB) Files Link
SRR15142310 29286571 5915887342 1876.67 Au6_S6_L001_R1_001.fastq.gz, Au6_S6_L001_R2_001.fastq.gz, SRR15142310… SRA
SRX11449742 SRP328366 RIP-Seq PAIRED
GSM5453668: cells B total chimeric eCLIP size-matched input, rep 2; Homo sapiens; RIP-Seq
Sample: SRS9489972
BioProject: PRJNA746604
BioSample: SAMN20222619
Platform: ILLUMINA
Instrument: Illumina NovaSeq 6000
Organism: Homo sapiens
Sample attributes
source_name: CD34+ cord blood
tissue: CD34+ cord blood
cell type: Lineage-depleted human cord blood cells sorted to collect CD34+ CB cells
rip antibody: none
inline barcode1: Ril19
Original files (1)
CD34+ cord blood
Runs (1)
Run Spots Bases Size (MB) Files Link
SRR15142311 26374635 5327676270 1675.44 Au7_S7_L001_R1_001.fastq.gz, Au7_S7_L001_R2_001.fastq.gz, SRR15142311… SRA
SRX11449743 SRP328366 RIP-Seq PAIRED
GSM5453669: cells B hsa-miR-130a targeted chimeric eCLIP; Homo sapiens; RIP-Seq
Sample: SRS9489973
BioProject: PRJNA746604
BioSample: SAMN20222618
Platform: ILLUMINA
Instrument: Illumina NovaSeq 6000
Organism: Homo sapiens
Sample attributes
source_name: CD34+ cord blood
tissue: CD34+ cord blood
cell type: Lineage-depleted human cord blood cells sorted to collect CD34+ CB cells
rip antibody: AGO2 clone 4F9 (Santa Cruz, sc-53521)
inline barcode1: Ril19
Original files (1)
CD34+ cord blood
Runs (1)
Run Spots Bases Size (MB) Files Link
SRR15142312 9445872 1908066144 583.01 Au13_S13_L001_R1_001.fastq.gz, Au13_S13_L001_R2_001.fastq.gz, SRR1514… SRA
SRX11449744 SRP328366 RIP-Seq PAIRED
GSM5453670: cells C hsa-miR-130a targeted chimeric eCLIP; Homo sapiens; RIP-Seq
Sample: SRS9489974
BioProject: PRJNA746604
BioSample: SAMN20222617
Platform: ILLUMINA
Instrument: Illumina NovaSeq 6000
Organism: Homo sapiens
Sample attributes
source_name: Kasumi-1
cell line: t(8;21) AML cell line Kasumi-1
rip antibody: AGO2 clone 4F9 (Santa Cruz, sc-53521)
inline barcode1: Ril19
Original files (1)
Kasumi-1
Runs (1)
Run Spots Bases Size (MB) Files Link
SRR15142313 7211775 1456778550 453.79 Au9_S9_L001_R1_001.fastq.gz, Au9_S9_L001_R2_001.fastq.gz, SRR15142313… SRA
SRX11542352 SRP328366 OTHER PAIRED
GSM5470531: Kasumi-1 total chimeric eCLIP; Homo sapiens; OTHER
Sample: SRS9577336
BioProject: PRJNA746604
BioSample: SAMN20370371
Platform: ILLUMINA
Instrument: Illumina NovaSeq 6000
Organism: Homo sapiens
Sample attributes
source_name: Kasumi-1
antibody manufacturer: AGO2 clone 4F9, Santa Cruz
tissue: t(8;21) AML cell line
inline barcode1: Ril19
Original files (1)
Kasumi-1
Runs (1)
Run Spots Bases Size (MB) Files Link
SRR15236468 62838139 12693304078 3903.21 Au1_S1_L001_R1_001.fastq.gz, Au1_S1_L001_R2_001.fastq.gz, SRR15236468… SRA
SRX11542353 SRP328366 OTHER PAIRED
GSM5470532: Kasumi-1 total chimeric eCLIP size-matched input; Homo sapiens; OTHER
Sample: SRS9577337
BioProject: PRJNA746604
BioSample: SAMN20370370
Platform: ILLUMINA
Instrument: Illumina NovaSeq 6000
Organism: Homo sapiens
Sample attributes
source_name: Kasumi-1
antibody manufacturer: AGO2 clone 4F9, Santa Cruz
tissue: t(8;21) AML cell line
inline barcode1: Ril19
Original files (1)
Kasumi-1
Runs (1)
Run Spots Bases Size (MB) Files Link
SRR15236469 49869528 10073644656 3206.93 Au5_S5_L001_R1_001.fastq.gz, Au5_S5_L001_R2_001.fastq.gz, SRR15236469… SRA
SRX13437823 SRP328366 RIP-Seq PAIRED
GSM5733559: cells B hsa-miR-130a targeted chimeric eCLIP_2; Homo sapiens; RIP-Seq
Sample: SRS11337245
BioProject: PRJNA746604
BioSample: SAMN24036810
Platform: ILLUMINA
Instrument: Illumina NovaSeq 6000
Organism: Homo sapiens
Sample attributes
source_name: CD34+ cord blood
tissue: CD34+ cord blood
cell type: Lineage-depleted human cord blood cells
rip antibody: AGO2 clone 4F9 (Santa Cruz, sc-53521)
inline barcode1: Inline barcode1: Ril19
Original files (1)
CD34+ cord blood
Runs (1)
Run Spots Bases Size (MB) Files Link
SRR17259466 12057828 2435681256 759.69 Au14_S14_L001_R1_001.fastq.gz, Au14_S14_L001_R2_001.fastq.gz, SRR1725… SRA

Linked Publications (1)

Data Files (9)

Accession File Name Stored Type Output Type Mapping Assembly Size Download
Au1_S1_L001_R1_001.fastq.gz OTHER 3.8 GB link
Au5_S5_L001_R1_001.fastq.gz OTHER 3.1 GB link
Au13_S13_L001_R1_001.fastq.gz RIP-Seq 583.0 MB link
Au14_S14_L001_R1_001.fastq.gz RIP-Seq 759.7 MB link
Au2_S2_L001_R1_001.fastq.gz RIP-Seq 2.2 GB link
Au3_S3_L001_R1_001.fastq.gz RIP-Seq 2.0 GB link
Au6_S6_L001_R1_001.fastq.gz RIP-Seq 1.8 GB link
Au7_S7_L001_R1_001.fastq.gz RIP-Seq 1.6 GB link
Au9_S9_L001_R1_001.fastq.gz RIP-Seq 453.8 MB link