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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 [TBL1XR1 KD]

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

PROVIDER: PRJNA750786 | ENA |

REPOSITORIES: ENA

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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

Project description:Gene expression profiling and proteome analysis of normal and malignant hematopoietic stem cells have firmly established the existence of shared core stemness properties. However, the 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 hematopoietic stem cell (HSC) self-renewal and lineage differentiation. Integration of mass spectrometry and chimeric AGO2 eCLIP-seq identify TBL1XR1 as a primary miR-130a target. TBL1XR1 loss of function impairs lymphoid differentiation and expands long-term (LT)-HSC. This post-transcriptional regulation by miR-130a is usurped in t(8;21) acute myeloid leukemia (AML). Reduction of miR-130a levels in t(8;21) AML cells results in altered chromatin binding and composition of the AML1-ETO complex, demonstrating that miR-130a is critical for maintaining the oncogenic molecular program mediated by AML1-ETO. Our study establishes that comprehensive identification of the miRNA targetome within primary tissue enables the discovery of novel genes and molecular networks underpinning stemness properties of normal and leukemic cells.

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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 [TBL1XR1 KD]

Project description: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.

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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 [miR-130a OE]

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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

Project description: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.

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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]

2022-03-08 | GSE181137 | GEO

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 [CUT&RUN]

Project description:Gene expression profiling and proteome analysis of normal and malignant hematopoietic stem cells have firmly established the existence of shared core stemness properties. However, the 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 hematopoietic stem cell (HSC) self-renewal and lineage differentiation. Integration of mass spectrometry and chimeric AGO2 eCLIP-seq identify TBL1XR1 as a primary miR-130a target. TBL1XR1 loss of function impairs lymphoid differentiation and expands long-term (LT)-HSC. This post-transcriptional regulation by miR-130a is usurped in t(8,21) acute myeloid leukemia (AML). Reduction of miR-130a levels in t(8,21) AML cells results in altered chromatin binding and composition of the AML1-ETO complex, demonstrating that miR-130a is critical for maintaining the oncogenic molecular program mediated by AML1-ETO. Our study establishes that comprehensive identification of the miRNA targetome within primary tissue enables the discovery of novel genes and molecular networks underpinning stemness properties of normal and leukemic cells.

2022-03-08 | GSE181136 | GEO

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

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

| PRJNA750785 | ENA

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

Project description:Identification of the Global miR-130a Targetome Reveals a Novel Role for TBL1XR1 in Hematopoietic Stem Cell Self-Renewal and t(8 21) AML

| PRJNA750775 | ENA

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]

Project description: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]

| PRJNA750784 | ENA

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

Project description: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

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