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A CLK3-HMGA2 alternative splicing axis impacts human hematopoietic stem cell molecular identity throughout development

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Homo sapiens

PROVIDER: GSE109093 | GEO | 2018/04/05

REPOSITORIES: GEO

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A CLK3-HMGA2 Alternative Splicing Axis Impacts Human Hematopoietic Stem Cell Molecular Identity throughout Development.

Project description:While gene expression dynamics have been extensively cataloged during hematopoietic differentiation in the adult, less is known about transcriptome diversity of human hematopoietic stem cells (HSCs) during development. To characterize transcriptional and post-transcriptional changes in HSCs during development, we leveraged high-throughput genomic approaches to profile miRNAs, lincRNAs, and mRNAs. Our findings indicate that HSCs manifest distinct alternative splicing patterns in key hematopoietic regulators. Detailed analysis of the splicing dynamics and function of one such regulator, HMGA2, identified an alternative isoform that escapes miRNA-mediated targeting. We further identified the splicing kinase CLK3 that, by regulating HMGA2 splicing, preserves HMGA2 function in the setting of an increase in let-7 miRNA levels, delineating how CLK3 and HMGA2 form a functional axis that influences HSC properties during development. Collectively, our study highlights molecular mechanisms by which alternative splicing and miRNA-mediated post-transcriptional regulation impact the molecular identity and stage-specific developmental features of human HSCs.

| S-EPMC5957284 | biostudies-literature

A CLK3-HMGA2 alternative splicing axis impacts human hematopoietic stem cell molecular identity throughout development [ChIP-seq]

Project description:While gene expression dynamics have been extensively catalogued during hematopoietic differentiation in the adult, less is known about transcriptome diversity of human hematopoietic stem cells (HSCs) during development. To characterize transcriptional and post-transcriptional changes in HSCs during development, we leveraged high-throughput genomic approaches to profile miRNAs, lincRNAs, and mRNAs. Our findings indicate that HSCs manifest distinct alternative splicing patterns in key hematopoietic regulators. Detailed analysis of the splicing dynamics and function of one such regulator, HMGA2, identified an alternative isoform that escapes miRNA-mediated targeting. We further identified the splicing kinase CLK3 that, by regulating HMGA2 splicing, preserves HMGA2 function in the setting of an increase in let-7 miRNA levels, delineating how CLK3 and HMGA2 form a functional axis that influences HSC properties during development. Collectively, our study highlights molecular mechanisms by which alternative splicing and miRNA-mediated post-transcriptional regulation impact the molecular identity and stage-specific developmental features of human HSCs.

2018-04-05 | GSE109091 | GEO

A CLK3-HMGA2 alternative splicing axis impacts human hematopoietic stem cell molecular identity throughout development (HPC-5F RNAseq)

2018-04-05 | GSE112486 | GEO

A CLK3-HMGA2 alternative splicing axis impacts human hematopoietic stem cell molecular identity throughout development [HSC and PROG miRNA profiling]

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A CLK3-HMGA2 alternative splicing axis impacts human hematopoietic stem cell molecular identity throughout development [BM low-input mRNA-seq]

2018-04-05 | GSE109090 | GEO

A CLK3-HMGA2 alternative splicing axis impacts human hematopoietic stem cell molecular identity throughout development [HSC and PROG RNA-seq]

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A CLK3-HMGA2 alternative splicing axis impacts human hematopoietic stem cell molecular identity throughout development

Project description:A CLK3-HMGA2 alternative splicing axis impacts human hematopoietic stem cell molecular identity throughout development

| PRJNA429638 | ENA

A CLK3-HMGA2 alternative splicing axis impacts human hematopoietic stem cell molecular identity throughout development [ChIP-seq]

Project description:A CLK3-HMGA2 alternative splicing axis impacts human hematopoietic stem cell molecular identity throughout development [ChIP-seq]

| PRJNA429649 | ENA

A CLK3-HMGA2 alternative splicing axis impacts human hematopoietic stem cell molecular identity throughout development (HPC-5F RNAseq)

Project description:A CLK3-HMGA2 alternative splicing axis impacts human hematopoietic stem cell molecular identity throughout development (HPC-5F RNAseq)

| PRJNA447939 | ENA

A CLK3-HMGA2 alternative splicing axis impacts human hematopoietic stem cell molecular identity throughout development [HSC and PROG RNA-seq]

Project description:A CLK3-HMGA2 alternative splicing axis impacts human hematopoietic stem cell molecular identity throughout development [HSC and PROG RNA-seq]

| PRJNA429647 | ENA

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