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The miR-290 and miR-302 clusters are essential for reprogramming of fibroblasts to induced pluripotent stem cells

ABSTRACT: The miR-290 and miR-302 clusters are essential for reprogramming of fibroblasts to induced pluripotent stem cells

PROVIDER: PRJNA1117417 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR29203904.fastq.gz	Fastqsanger.gz
	SRR29203905.fastq.gz	Fastqsanger.gz
	SRR29203906.fastq.gz	Fastqsanger.gz
	SRR29203907.fastq.gz	Fastqsanger.gz
	SRR29203908.fastq.gz	Fastqsanger.gz

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The miR-290 and miR-302 clusters are essential for reprogramming of fibroblasts to induced pluripotent stem cells

Project description:The miR-290 and miR-302 clusters of microRNAs are highly expressed in naïve and primed pluripotent stem cells, respectively. Ectopic expression of the embryonic stem cell-specific cell cycle regulating (ESCC) family of microRNAs arising from these two clusters dramatically enhances the reprogramming of both mouse and human somatic cells to induced pluripotency. Here, we used genetic knockouts to dissect the requirement for the miR-290 and miR-302 clusters during the reprogramming of mouse fibroblasts into induced pluripotent stem cells (iPSCs) with retrovirally introduced Oct4, Sox2, and Klf4. Knockout of either cluster alone did not negatively impact the efficiency of reprogramming. Resulting cells appeared identical to their embryonic stem cell counterparts. Notably miR-290 knockout cells showed a compensatory increase in miR-302 expression and the combined loss of both clusters blocked the formation of iPSCs. While rare double knockout clones could be isolated, they showed a dramatically reduced proliferation rate, a persistent inability to fully silence the exogenously introduced pluripotency factors, and a transcriptome distinct from individual miR-290 or miR-302 mutant ESC and iPSCs. Taken together, our data show that miR-290 and miR-302 are essential yet interchangeable in reprograming to the induced pluripotent state.

2025-01-10 | GSE268461 | GEO

Expression analysis of OSK and Sall4+OSK reprogramming cells sorted for expression of miR-290 and/or miR-302.

2014-03-31 | GSE54341 | GEO

Expression analysis of OSK and Sall4+OSK reprogramming cells sorted for expression of miR-290 and/or miR-302.

Project description:MEFs were infected with Oct4, Sox2, Klf4 (+/- Sall4), sorted for miR-290/302 reporter expression at day 9 (OSK) or 12 (Sall4+OSK), and then profiled. Resulting iPSCs were also profiled. Mouse ES cells were differentiated and sorted for miR-290/302 reporter expression during Fgf/Activin differentiation (day 4 or day 7). Performed in biological triplicate. Biological triplicate samples represent three independent lines. Total RNA collected with Trizol. All processing conducted at the UCLA Neuroscience Genomics Core. MouseRef-8 v2.0 Expression BeadChips.

2014-03-31 | E-GEOD-54341 | biostudies-arrayexpress

Pluripotency-associated miR-290/302 family of microRNAs promote the dismantling of naive pluripotency

Project description:Upon RNA profiling of WT and Dgcr8-/- mESCs in 2iL and differentiation for 48 hours, miRNAs are proved to be important for the transcriptional changes during ESC exiting from pluripotency. Further miRNA sequencing of WT ESCs in different timepoints revealed that miRNAs expression changes dynamically during ESC to EpiLC transition and identified miR-290/302 as key miRNAs facilitating the dismantling of naive pluripotency.

2018-11-29 | GSE123096 | GEO

The eutherian-specific miR-290/miR-371 cluster modulates placental growth and maternal-fetal transport

Project description:A family of vertebrate-specific microRNAs called the ESCC microRNAs regulates proliferation and differentiation of embryonic stem cells. The ESCC microRNAs arise from two genetic loci in mammals, the miR-290/miR-371 and miR-302 loci. While the miR-302 locus is found broadly among vertebrates, the miR-290/miR-371 locus is unique to eutherian species, suggesting a role in placental development. Here, we evaluate that role. A knockin reporter for the mouse miR-290 gene is expressed throughout the embryo until gastrulation, at which time it becomes specifically expressed in extraembryonic tissues and the germline. In the placenta, expression is limited to the trophoblast lineage, where it remains highly expressed until birth. Deletion of the miR-290 gene results in reduced trophoblast progenitor cell proliferation and a reduced DNA content in endoreduplicating trophoblast giant cells. A reduction in placental size precedes a reduction in fetal size and prenatal death of most knockout embryos. The vascular labyrinth shows disorganization with thickening of the barrier between maternal and fetal blood associated with reduced diffusion of a radioactive tracer. Multiple mRNA targets of the cluster miRNAs are upregulated. Together, these data uncover a critical function for the miR-290 in the regulation of a network of genes required for normal placental development, suggesting a central role for this microRNA cluster in the evolution of eutherian species.

2017-03-04 | GSE95687 | GEO

Targeting oncogenic microRNAs from the miR-371~373 and miR-302/367 clusters in malignant germ cell tumours causes growth inhibition through cell cycle disruption

Project description:Background. MiR-371~373 and miR-302/367 cluster over-expression occurs in all malignant- GCTs, regardless of age (paediatric/adult), site (gonadal/extragonadal), or subtype [seminoma, yolk sac tumour (YST), embryonal carcinoma (EC)]. Six of eight microRNAs from these clusters contain the seed ‘AAGUGC’, determining mRNA targeting. Here we sought to identify the significance of these observations by targeting these microRNAs functionally. Methods. We targeted miR-371~373 and/or miR-302/367 clusters in malignant-GCT cell lines, using CRISPR-Cas9, gapmer primary miR-302/367 transcripts inhibition, and peptide- nucleic-acid (PNA) or locked-nucleic-acid (LNA)-DNA inhibition targeting miR-302a-d-3p, and undertook relevant functional assays. Results. MiR-302/367 cluster microRNAs made the largest contribution to AAGUGC seed abundance in malignant-GCT cells, regardless of subtype (seminoma/YST/EC). Following unsuccessful use of CRISPR-Cas9, gapmer, and PNA systems, LNA-DNA-based targeting resulted in growth inhibition in seminoma and YST cells. This was associated with de- repression of multiple mRNAs targeted by ‘AAGUGC’ seed-containing microRNAs, with pathway analysis confirming predominant disruption of Rho-GTPase signaling, vesicle organization/transport, and cell-cycle regulation, findings corroborated in clinical samples. Further LNA-DNA inhibitor studies confirmed direct cell-cycle effects, with increase of cells in G0/G1-phase and decrease in S-phase. Conclusion. Targeting of specific miR-371~373 and miR-302/367 microRNAs in malignant- GCTs demonstrated their functional significance, with growth inhibition mediated through cell-cycle disruption.

2024-08-01 | E-MTAB-13323 | biostudies-arrayexpress

Pluripotency-associated miR-290/302 family of microRNAs promote the dismantling of naive pluripotency

Project description:Pluripotency-associated miR-290/302 family of microRNAs promote the dismantling of naive pluripotency

| PRJNA507525 | ENA

miR-302-367 regulates cardiomycyte proliferation and differentiation during development

Project description:To define the role of miR-302-367 cluster in cardiac development, we overexpressed miR-302-367 cluster in mouse heart by using R26R-miR-302-367; Nkx2.5-Cre mice. This data set contains the microarrays examining gene expression in the hearts of R26R-miR-302-367; Nkx2.5-Cre mice at postnatal day 14.

2015-01-01 | GSE54988 | GEO

Expression profiling in miR-290 6dt1 mammary tumors

Project description:mRNA expression data from mammary tumors extracted 30 days after orthotopic injection of miR-290-expressing and negative control 6dt1 cells into female FVB/N mice. At 6 weeks of age, FVB/N female mice were orthotopically injected with 1.0x10E5 6dt1 cells, either expressing miR-290 or a negative control RNA construct. 4 negative control tumors and 3 miR-290 tumors were analyzed.

2013-01-15 | E-GEOD-43485 | biostudies-arrayexpress

miR-302-367 regulates cardiomycyte proliferation and differentiation during development

2015-01-01 | E-GEOD-54988 | biostudies-arrayexpress