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GSE29328
Mus musculus
19 Downloadable Samples
Description
We used microarrays to assess the global gene expression profiles of cancer stem cells which were isolated from cutaneous squamous cell carcinomas which developed when WT, TGF beta receptor II ko, FAK KO, and TGF beta receptor II/FAK double KO were subjected to continuous DMBA treatment.
Publication Title
Tumor-initiating stem cells of squamous cell carcinomas and their control by TGF-β and integrin/focal adhesion kinase (FAK) signaling.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 5 Downloadable Samples
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Specific microRNAs are preferentially expressed by skin stem cells to balance self-renewal and early lineage commitment.
Sample Metadata Fields
Sex, Specimen part, Treatment
View Samples- Mus musculus
- 3 Downloadable Samples
Description
Increasing evidence suggests that microRNAs may play important roles in regulating self-renewal and differentiation in mammalian stem cells (SCs). Here, we explore this issue in skin. We first characterize microRNA expression profiles of skin SCs versus their committed proliferative progenies and identify a microRNA subset associating with stemness. Of these, miR-125b is dramatically downregulated in early SC-progeny. We engineer an inducible mice system and show that when miR-125b is sustained in SC-progenies, tissue balance is reversibly skewed towards stemness at the expense of epidermal, oil-gland and HF differentiation. Using gain-and-loss of function in vitro, we further implicate miR-125b as a repressor of SC differentiation. In vivo, transcripts repressed upon miR-125b induction are enriched >700% for predicted miR-125b targets normally downregulated upon SC-lineage commitment. We verify some of these miR-125b targets, and show that Blimp1 and VDR in particular can account for many tissue imbalances we see when miR-125b is deregulated.
Publication Title
Specific microRNAs are preferentially expressed by skin stem cells to balance self-renewal and early lineage commitment.
Sample Metadata Fields
Sex, Specimen part, Treatment
View Samples- Mus musculus
- 4 Downloadable Samples
Description
During development, a polarized sheet of epidermal cells undergoes stratification and differentiation to produce the skin barrier. Through mechanisms poorly understood, the process involves adhesion and Notch signaling. To elucidate how epidermal embryogenesis is governed, we conditionally targeted transcription factor serum response factor (SRF), which has been shown to be essential for proper epidermal differentiation in vitro and in vivo. Seeking mechanism, we identified actomyosin-related genes as well-known SRF targets downregulated shortly after ablation. We show that this results in a diminished cortical actomyosin network which fails to regulate the transition of cells from the basal proliferative layer to the suprabasal differentiating layer resulting in an inability of cells to properly execute stratification and differentiation.
Publication Title
Developmental roles for Srf, cortical cytoskeleton and cell shape in epidermal spindle orientation.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 2 Downloadable Samples
Description
Increasing evidence suggests that microRNAs may play important roles in regulating self-renewal and differentiation in mammalian stem cells (SCs). Here, we explore this issue in skin. We first characterize microRNA expression profiles of skin SCs versus their committed proliferative progenies and identify a microRNA subset associating with stemness. Of these, miR-125b is dramatically downregulated in early SC-progeny. We engineer an inducible mice system and show that when miR-125b is sustained in SC-progenies, tissue balance is reversibly skewed towards stemness at the expense of epidermal, oil-gland and HF differentiation. Using gain-and-loss of function in vitro, we further implicate miR-125b as a repressor of SC differentiation. In vivo, transcripts repressed upon miR-125b induction are enriched >700% for predicted miR-125b targets normally downregulated upon SC-lineage commitment. We verify some of these miR-125b targets, and show that Blimp1 and VDR in particular can account for many tissue imbalances we see when miR-125b is deregulated.
Publication Title
Specific microRNAs are preferentially expressed by skin stem cells to balance self-renewal and early lineage commitment.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 5 Downloadable Samples
Description
Polycomb protein group (PcG)-dependent trimethylation on H3-K27(H3K27me3) regulates identity of embryonic stem cells (SCs). How H3K27me3 governs adult SCs and tissue development is unclear. Here, we conditionally target H3-K27-methyltransferases Ezh2 and Ezh1 to address their roles in mouse skin homeostasis. Postnatal phenotypes appear only in doubly-targeted skin, where H3K27me3 is abolished, revealing functional redundancy in EZH1/2 proteins. Surprisingly, while Ezh1/2-null hair follicles (HFs) arrest morphogenesis and degenerate due to defective proliferation and increased apoptosis, epidermis hyperproliferates and survives engraftment. mRNA-microarray studies reveal that despite these striking phenotypic differences, similar genes are upregulated in HF and epidermal Ezh1/2-null progenitors. Featured prominently are a) PcG-controlled non-skin lineage genes, whose expression is still significantly lower than in native tissues, and b) the PcG-regulated Ink4a/Inkb/Arf locus. Interestingly, even though Ink4a/Arf/Ink4b genes are fully activated in HF cells, they only partially so in epidermal-progenitors. Importantly, transduction of Ink4b/Ink4a/Arf shRNAs restores proliferation/survival of Ezh1/2-null HF progenitors in vitro, pointing towards the relevance of this locus to the observed HF phenotypes. Our findings reveal new insights into Polycomb-dependent tissue control and provide a new twist to how different progenitors within one tissue respond to loss of H3K27me3.
Publication Title
EZH1 and EZH2 cogovern histone H3K27 trimethylation and are essential for hair follicle homeostasis and wound repair.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Mus musculus
- 2 Downloadable Samples
Description
Mouse hair follicles (HFs) undergo synchronized cycles. Cyclical regeneration and hair growth is fueled by stem cells (SCs). During the rest phase, the HF-SCs remain quiescent due to extrinsic inhibitory signals within the niche. As activating cues accumulate, HF-SCs become activated, proliferate, and grow downward to form transient-amplifying matrix progenitor cells. We used microarrays to detect the relative levels of global gene expression underlying the states of hair follicle stem cells and their transient-amplifying progeny before differentiation.
Publication Title
Genome-wide maps of histone modifications unwind in vivo chromatin states of the hair follicle lineage.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 4 Downloadable Samples
Description
We identify numerous miR-203 in vivo targets that are highly enriched for the promotion of cell cycle and cell division. Importantly, individual targets including p63, Skp2 and Msi2 play distinct roles downstream of miR-203 to regulate the cell cycle and long-term proliferation. Together, our findings reveal rapid and widespread impact of miR-203 on the self-renewal program during the epidermal differentiation and provide mechanistic insights for the potent role of miR-203 where coordinated repression of multiple targets is required for the function of this miRNA.
Publication Title
Rapid and widespread suppression of self-renewal by microRNA-203 during epidermal differentiation.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 8 Downloadable Samples
Description
Uniparental parthenotes are considered an unwanted byproduct of in vitro fertilization. In utero parthenote development is severely compromised by defective organogenesis and in particular by defective cardiogenesis. Although developmentally compromised, apparently pluripotent stem cells can be derived from parthenogenetic blastocysts. Here we hypothesized that nonembryonic parthenogenetic stem cells (PSCs) can be directed toward the cardiac lineage and applied to tissue-engineered heart repair. We first confirmed similar fundamental properties in murine PSCs and embryonic stem cells (ESCs), despite notable differences in genetic (allelic variability) and epigenetic (differential imprinting) characteristics. Haploidentity of major histocompatibility complexes (MHCs) in PSCs is particularly attractive for allogeneic cell-based therapies. Accordingly, we confirmed acceptance of PSCs in MHC-matched allotransplantation. Cardiomyocyte derivation from PSCs and ESCs was equally effective. The use of cardiomyocyte-restricted GFP enabled cell sorting and documentation of advanced structural and functional maturation in vitro and in vivo. This included seamless electrical integration of PSC-derived cardiomyocytes into recipient myocardium. Finally, we enriched cardiomyocytes to facilitate engineering of force-generating myocardium and demonstrated the utility of this technique in enhancing regional myocardial function after myocardial infarction. Collectively, our data demonstrate pluripotency, with unrestricted cardiogenicity in PSCs, and introduce this unique cell type as an attractive source for tissue-engineered heart repair.
Publication Title
Parthenogenetic stem cells for tissue-engineered heart repair.
Sample Metadata Fields
Specimen part
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