GSE180129
GSE GEOGlobal 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
Relations
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- Sequenced reads were reformatted to include randomers in read headers with umi_tools (1.0.0).
- Args: --random-seed 1 --bc-pattern NNNNNNNNNN
- Reads were then trimmed with cutadapt (1.14).
- 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/)
- Reads were then trimmed again with cutadapt (1.14) to remove double-ligation events.
- 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/)
- For targeted miR-130a datasets, reads that did not contain the primer sequence (CAGUGCAAUGUUAAAAGGGCAU) were filtered out.
- For total chimeric eCLIP datasets, 10nt from the 3'end of Read1 was trimmed with umi_tools.
Supplementary Files (2)
GEO Samples (9)
Dataset Citations (1)
SRA Experiments (9) and Runs (9)
Total: 16685 MBSample attributes
Original files (1)
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 |
Sample attributes
Original files (1)
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 |
Sample attributes
Original files (1)
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 |
Sample attributes
Original files (1)
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 |
Sample attributes
Original files (1)
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 |
Sample attributes
Original files (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 |
Sample attributes
Original files (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 |
Sample attributes
Original files (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 |
Sample attributes
Original files (1)
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 |