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MiR expression profiling of mouse hematopoietic stem and progenitor populations [miRNA]

ABSTRACT: Several individual miRNAs (miRs) have been implicated as potent regulators of important processes during normal and malignant hematopoiesis. In addition, many miRs have been shown to fine-tune intricate molecular networks, in concert with other regulatory elements. In order to study hematopoietic networks as a whole, we first created a comprehensive map of global miR expression during early murine hematopoiesis. Next, we determined the copy number per cell for each miR in each of the examined stem and progenitor cell types. As data is emerging indicating that miRs function robustly mainly when they are expressed above a certain threshold (~100 copies per cell), our database provides a resource for determining which miRs are expressed at a potentially functional level in each cell type. Finally, we combine our miR expression map with matched mRNA expression data and external prediction algorithms, using a Bayesian modeling approach to create a global landscape of predicted miR-mRNA interactions within each of these hematopoietic stem and progenitor cell subsets. This approach identifies several interaction networks comprising a “stemness” signature in the most primitive hematopoietic stem cell (HSC) populations, as well as “myeloid” patterns associated with two branches of myeloid development. Six populations of mouse hematopoietic stem and progenitors have been analyzed (LT-HSC, ST-HSC, MPP, CMP, GMP, MEP). 2-3 replicates are included for each sample.

ORGANISM(S): Mus musculus

SUBMITTER: Curt Civin

PROVIDER: E-GEOD-49167 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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miR expression profiling of mouse hematopoietic stem and progenitor populations [mRNA]

Project description:Several individual miRNAs (miRs) have been implicated as potent regulators of important processes during normal and malignant hematopoiesis. In addition, many miRs have been shown to fine-tune intricate molecular networks, in concert with other regulatory elements. In order to study hematopoietic networks as a whole, we first created a comprehensive map of global miR expression during early murine hematopoiesis. Next, we determined the copy number per cell for each miR in each of the examined stem and progenitor cell types. As data is emerging indicating that miRs function robustly mainly when they are expressed above a certain threshold (~100 copies per cell), our database provides a resource for determining which miRs are expressed at a potentially functional level in each cell type. Finally, we combine our miR expression map with matched mRNA expression data and external prediction algorithms, using a Bayesian modeling approach to create a global landscape of predicted miR-mRNA interactions within each of these hematopoietic stem and progenitor cell subsets. This approach identifies several interaction networks comprising a “stemness” signature in the most primitive hematopoietic stem cell (HSC) populations, as well as “myeloid” patterns associated with two branches of myeloid development. Six populations of mouse hematopoietic stem and progenitors have been analyzed (LT-HSC, ST-HSC, MPP, CMP, GMP, MEP). 2-3 replicates are included for each sample.

2013-07-24 | E-GEOD-49169 | biostudies-arrayexpress

miR expression profiling of mouse hematopoietic stem and progenitor populations

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

2013-07-24 | E-GEOD-49170 | biostudies-arrayexpress

miR expression profiling of mouse hematopoietic stem and progenitor populations [mRNA]

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miR expression profiling of mouse hematopoietic stem and progenitor populations [miRNA]

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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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Attenuation of miR-126 activity expands HSC in vivo without exhaustion

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