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accession-icon GSE55673
Alternative Splicing of MBD2 Supports Self-Renewal in Human Pluripotent Stem Cells [HG-U133_Plus_2]
  • organism-icon Homo sapiens
  • sample-icon 16 Downloadable Samples
  • Technology Badge Icon Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)

Description

Using global gene expression and proteomic analyses, we identified a molecular signature in human embryonic and induced pluripotent stem cells that suggested a central regulatory role for RNA splicing in self-renewal. Through genetic and biochemical approaches, we established reciprocal functional links between the master regulatory factor OCT4 and SFRS2, a member of the serine/arginine-rich family of splicing factors. SFRS2 regulates expression of two isoforms of the methyl-CpG-binding protein MBD2 that play opposing roles in human ESC and during the reprogramming of fibroblasts. Both the MBD2a isoform expressed in fibroblasts and the MBD2c isoform found in pluripotent cells bind OCT4 and NANOG promoters in human ESC, but only MBD2a interacts with NuRD chromatin remodeling factors. Members of the miR-301 and miR-302 families provide additional regulation by targeting SFRS2 and the somatic specific MBD2a isoform. These data are consistent with a model in which OCT4, SFRS2, and MBD2 participate in a positive feedback loop to regulate proteome diversity in support of self-renewal in pluripotent cells.

Publication Title

Alternative splicing of MBD2 supports self-renewal in human pluripotent stem cells.

Sample Metadata Fields

Specimen part

View Samples
accession-icon GSE31409
Lentiviral vector-based insertional mutagenesis identifies new clinically relevant cancer genes involved in the pathogenesis of hepatocellular carcinoma
  • organism-icon Mus musculus
  • sample-icon 29 Downloadable Samples
  • Technology Badge Icon Affymetrix Mouse Gene 1.0 ST Array (mogene10st)

Description

We devised a novel insertional mutagenesis approach based on lentiviral vectors to induce hepatocellular carcinoma in three mouse models and identified four novel cancer initiating genes. Two genes are the well characterized Braf and Sos1, while the other two are Fign, encoding an AAA ATPase whose functions are poorly understood, and the complex Dlk1-Dio3 imprinted region which has been recently implicated in cancer and stemness. Activation of Fign or Braf and upregulation of the Dlk1-Dio3 imprinted region are functionally interconnected and may altogether control cell transformation, stemness and energy metabolism. Moreover, all the genes identified play a relevant role in human hepatocarcinogenesis as their expression levels and/or transcriptional signatures induced by their deregulation predict a different clinical outcome in hepatocellular carcinoma patients. These series consists of mRNA expression microarray data (The GeneChip Mouse Gene 1.0 ST Array, Affymetrix) from 8 non-tumoral liver and 21 hepatocellular carcinoma induced by insertional mutagenesis.

Publication Title

Lentiviral vector-based insertional mutagenesis identifies genes associated with liver cancer.

Sample Metadata Fields

Specimen part

View Samples
accession-icon SRP049340
Integrative analyses of human reprogramming reveal dynamic nature of induced pluripotency [mRNA-Seq]
  • organism-icon Homo sapiens
  • sample-icon 166 Downloadable Samples
  • Technology Badge IconIlluminaHiSeq2500, IlluminaHiSeq2000

Description

Induced pluripotency is a promising avenue for disease modeling and therapy, but the molecular principles underlying this process, particularly in human cells, remain poorly understood due to donor-to-donor variability and intercellular heterogeneity. Here we constructed and characterized a clonal, inducible human reprogramming system that provides a reliable source of cells at any stage of the process. This system enabled integrative transcriptional and epigenomic analysis across the human reprogramming timeline at high resolution. We observed distinct waves of gene network activation, including the ordered re-activation of broad developmental regulators followed by early embryonic patterning genes and culminating in the emergence of a signature reminiscent of pre-implantation stages. Moreover, complementary functional analyses allowed us to identify and validate novel regulators of the reprogramming process. Altogether, this study sheds light on the molecular underpinnings of induced pluripotency in human cells and provides a robust cell platform for further studies. Overall design: mRNA sequencing of primary and secondary fibroblasts with reference BJ (supplementary file fibroblasts), reprogramming intermendiates from untreated hiF-T reprogramming (supplementary file reprogramming), or selective time points upon LSD1 inhibitor treatment (supplementary file LSD1i). RNA samples used for mRNA sequencing are the same used for smallRNA sequencing.

Publication Title

Integrative Analyses of Human Reprogramming Reveal Dynamic Nature of Induced Pluripotency.

Sample Metadata Fields

No sample metadata fields

View Samples
accession-icon SRP058773
Integrative analyses of human reprogramming reveal dynamic nature of induced pluripotency [smartseq2]
  • organism-icon Homo sapiens
  • sample-icon 52 Downloadable Samples
  • Technology Badge IconIlluminaHiSeq2500

Description

Induced pluripotency is a promising avenue for disease modeling and therapy, but the molecular principles underlying this process, particularly in human cells, remain poorly understood due to donor-to-donor variability and intercellular heterogeneity. Here we constructed and characterized a clonal, inducible human reprogramming system that provides a reliable source of cells at any stage of the process. This system enabled integrative transcriptional and epigenomic analysis across the human reprogramming timeline at high resolution. We observed distinct waves of gene network activation, including the ordered re-activation of broad developmental regulators followed by early embryonic patterning genes and culminating in the emergence of a signature reminiscent of pre-implantation stages. Moreover, complementary functional analyses allowed us to identify and validate novel regulators of the reprogramming process. Altogether, this study sheds light on the molecular underpinnings of induced pluripotency in human cells and provides a robust cell platform for further studies. Overall design: single cell RNA-seq profiles from 52 unfractionated hiF-T cells after 10 days of reprogramming

Publication Title

Integrative Analyses of Human Reprogramming Reveal Dynamic Nature of Induced Pluripotency.

Sample Metadata Fields

No sample metadata fields

View Samples
accession-icon SRP136698
A CLK3-HMGA2 alternative splicing axis impacts human hematopoietic stem cell molecular identity throughout development (HPC-5F RNAseq)
  • organism-icon Homo sapiens
  • sample-icon 8 Downloadable Samples
  • Technology Badge IconIllumina HiSeq 2500

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. Overall design: RNA-seq of HPC-5F cells transduced with a control (CTRL), HMGA2-L (LONG), HMGA2-S (SHORT) or CLK3 ORF lentiviral over-expression vectors.

Publication Title

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

Sample Metadata Fields

Specimen part, Subject

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accession-icon GSE45715
Genome-wide analysis of BRCA1 and PALB2
  • organism-icon Homo sapiens
  • sample-icon 8 Downloadable Samples
  • Technology Badge IconIllumina HumanHT-12 V4.0 expression beadchip

Description

This SuperSeries is composed of the SubSeries listed below.

Publication Title

Genome-wide analysis reveals a role for BRCA1 and PALB2 in transcriptional co-activation.

Sample Metadata Fields

Specimen part, Disease, Cell line

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accession-icon GSE45713
Genome-wide analysis of BRCA1 and PALB2 [TNF-alpha stimulation]
  • organism-icon Homo sapiens
  • sample-icon 4 Downloadable Samples
  • Technology Badge IconIllumina HumanHT-12 V4.0 expression beadchip

Description

Breast and ovarian cancer susceptibility genes, BRCA1 and PALB2 have enigmatic roles in cellular growth and mammalian development. While these genes are essential for growth during early developmental programs, inactivation later in adulthood leads to increased growth and formation of tumors, leading to their designation as tumor suppressors. We performed genome-wide analysis assessing their chromatin residence and gene expression responsiveness using high throughput sequencing in breast epithelial cells. These experiments revealed a critical role for BRCA1 and PALB2 in transcriptional responsiveness to NF-kB, a crucial mediator of growth and inflammatory response during development and cancer. Importantly, we also uncovered a vital role for these proteins in response to retinoic acid (RA), a growth inhibitory signal in breast cancer cells, which may constitute the basis for their tumor suppressor activity.

Publication Title

Genome-wide analysis reveals a role for BRCA1 and PALB2 in transcriptional co-activation.

Sample Metadata Fields

Specimen part, Cell line

View Samples
accession-icon GSE45714
Genome-wide analysis of BRCA1 and PALB2 [RA stimulation]
  • organism-icon Homo sapiens
  • sample-icon 4 Downloadable Samples
  • Technology Badge IconIllumina HumanHT-12 V4.0 expression beadchip

Description

Breast and ovarian cancer susceptibility genes, BRCA1 and PALB2 have enigmatic roles in cellular growth and mammalian development. While these genes are essential for growth during early developmental programs, inactivation later in adulthood leads to increased growth and formation of tumors, leading to their designation as tumor suppressors. We performed genome-wide analysis assessing their chromatin residence and gene expression responsiveness using high throughput sequencing in breast epithelial cells. These experiments revealed a critical role for BRCA1 and PALB2 in transcriptional responsiveness to NF-kB, a crucial mediator of growth and inflammatory response during development and cancer. Importantly, we also uncovered a vital role for these proteins in response to retinoic acid (RA), a growth inhibitory signal in breast cancer cells, which may constitute the basis for their tumor suppressor activity.

Publication Title

Genome-wide analysis reveals a role for BRCA1 and PALB2 in transcriptional co-activation.

Sample Metadata Fields

Specimen part, Cell line

View Samples
accession-icon GSE41529
Genome-wide analysis of the SNAPc complex
  • organism-icon Homo sapiens
  • sample-icon 12 Downloadable Samples
  • Technology Badge IconIllumina HumanHT-12 V4.0 expression beadchip

Description

This SuperSeries is composed of the SubSeries listed below.

Publication Title

Requirement for SNAPC1 in transcriptional responsiveness to diverse extracellular signals.

Sample Metadata Fields

Cell line, Treatment

View Samples
accession-icon GSE41528
Genome-wide analysis of the SNAPc complex [Illumina array]
  • organism-icon Homo sapiens
  • sample-icon 12 Downloadable Samples
  • Technology Badge IconIllumina HumanHT-12 V4.0 expression beadchip

Description

The small nuclear RNA (snRNA)-activating protein complex (SNAPc) is a basal transcription factor that mediates the transcriptional activation of snRNAs. Here, we describe the genome-wide occupancy of the SNAPC1_and SNAPC4 subunits of SNAPc. While the SNAPC4 occupancy was in accord with the role for SNAPc in snRNA transcription, SNAPC1_displayed a broader genomic profile mirroring that of RNA polymerase II at highly active protein-coding genes. Our functional analysis revealed a role for SNAPC1_in regulation of both basal and activator-induced transcription of protein-coding genes. These studies expand the role for SNAPC1_beyond its regulation of snRNA transcription.

Publication Title

Requirement for SNAPC1 in transcriptional responsiveness to diverse extracellular signals.

Sample Metadata Fields

Cell line, Treatment

View Samples
...

refine.bio is a repository of uniformly processed and normalized, ready-to-use transcriptome data from publicly available sources. refine.bio is a project of the Childhood Cancer Data Lab (CCDL)

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Cite refine.bio

Casey S. Greene, Dongbo Hu, Richard W. W. Jones, Stephanie Liu, David S. Mejia, Rob Patro, Stephen R. Piccolo, Ariel Rodriguez Romero, Hirak Sarkar, Candace L. Savonen, Jaclyn N. Taroni, William E. Vauclain, Deepashree Venkatesh Prasad, Kurt G. Wheeler. refine.bio: a resource of uniformly processed publicly available gene expression datasets.
URL: https://www.refine.bio

Note that the contributor list is in alphabetical order as we prepare a manuscript for submission.

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