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GSE181137

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Identification of the Global miR-130a Targetome Reveals a Novel Role for TBL1XR1 in Hematopoietic Stem Cell Self-Renewal and t(8;21) AML [miR130aKD_Kasumi]

Organism: Homo sapiens
Platform: GPL16791
Samples: 6
Experiment Types:
Expression profiling by high throughput sequencing
Submitted: Jul 29 2021
Last Updated: Jul 01 2024
Status: Public on Mar 08 2022
Contact: Alexander,James,Murison (University Health Network)

Relations

SubSeries of: GSE181140 BioProject: https://www.ncbi.nlm.nih.gov/bioproject/PRJNA750784

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 identified miR-130a as a regulator of HSC self-renewal and differentiation. Enforced expression of miR-130a impaired lymphoid differentiation and expanded long-term HSC. Integration of protein mass spectrometry and chimeric AGO2 eCLIP-seq identified TBL1XR1 as a primary miR-130a target, whose loss of function phenocopied miR-130a overexpression. Moreover, we found that miR-130a is highly expressed in t(8;21) AML where it is critical for maintaining the oncogenic molecular program mediated by AML1-ETO. Our study establishes that identification of the comprehensive miRNA targetome within primary cells enables discovery of novel genes and molecular networks underpinning stemness properties of normal and leukemic cells.

Overall Design

Characterization of gene expression changes following miR-130a knock-down in Kasumi-1 cells. >>>Submitter states: Raw data is being submitted separately to the EGA as we require controlled access for some data.<<<

Analysis (1 step)

View Data Processing
Processing steps for GSE181137
  1. Raw Reads were aligned using STAR against known GENCODE 32 transcripts

Supplementary Files (1)

GSE181137_RAW.tar Download
GEO Samples (6)

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

Linked Publications (1)