Identification of drugs that enhance skin repair using dermal stem cell-based screens
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ABSTRACT:
ORGANISM(S): Rattus norvegicus
SUBMITTER: Freda Miller
PROVIDER: E-GEOD-73329 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
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Project description:Here, we asked whether we could identify pharmacological agents that enhance endogenous stem cell function to promote skin repair, focusing on SKPs (skin-derived precursors) a dermal precursor cell population. Libraries of compounds already used in humans were screened for their ability to enhance the self-renewal of human and rodent SKPs. We identified and validated 5 such compounds, and showed that two of them, alprostadil and trimebutine maleate, enhanced the repair of full thickness skin wounds in middle-aged mice. Moreover, SKPs isolated from drug-treated skin displayed long-term increases in self-renewal when cultured in basal growth medium without drugs. Both alprostadil and trimebutine maleate likely mediated increases in SKPs self-renewal by moderate hyperactivation of the MEK-ERK pathway. These findings identify candidates for potential clinical use in human skin repair, and provide support for the idea that pharmacological activation of endogenous tissue precursors represents a viable therapeutic strategy. We obtained three independent isolates of SKPs from newborn Sprague-Dawley rat pups. Secondary SKPs spheres were dissociated, treated with 100 nM of alprostadil, trimebutine maleate or 100 nM of both trimebutine maleate and trametinib for 24 hour. RNA samples deriving from these cells were analyzed on the Affymetrix GeneChip Rat Gene 2.0 ST Array.
2015-12-24 | E-GEOD-73328 | biostudies-arrayexpress
Project description:Recent reports of directed reprogramming have raised questions about the stability of cell lineages. Here, we have addressed this issue, focusing upon skin-derived precursors (SKPs), a dermally-derived precursor cell. We show by lineage tracing that murine SKPs from dorsal skin originate from mesenchymal and not neural crest-derived cells. These mesenchymally-derived SKPs can, without genetic manipulation, generate functional Schwann cells, a neural crest cell type, and are highly similar at the transcriptional level to Schwann cells isolated from the peripheral nerve. This is not a mouse-specific phenomenon, since human SKPs that are highly similar at the transcriptome level can be made from facial (neural crest-derived) and foreskin (mesodermally-derived) dermis, and the mesodermally-derived SKPs can make myelinating Schwann cells. Thus, non-neural crest-derived mesenchymal precursors can differentiate into bona fide peripheral glia in the absence of genetic manipulation, suggesting that developmentally-defined lineage boundaries are more flexible than widely thought. We obtained 3 independent samples of nerve Schwann cells, SKP-derived Schwann cells, and Dorsal Trunk SKPs, each, from adult SD rats. Primary cells were isolated and cultured, and RNA was collected from those cultured samples. RNA samples deriving from these cells were analyzed on the Affymetrix Rat Gene 1.0 ST Array.
2014-08-01 | E-GEOD-57505 | biostudies-arrayexpress
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2014-08-01 | E-GEOD-57519 | biostudies-arrayexpress
Project description:The experiment was designed to identify differential gene expression due to dominant negative mutation of the Sox18 gene in the ragged Opossum spontaneous mouse mutant. Gene expression was analysed after whole RNA isolation in dermal spheres as hair follicle inductive mesenchyme tissue, and was intended to identify gene expression patterns associated with alteration of hair induction post Sox18 mutation.
2017-05-16 | E-MTAB-5673 | biostudies-arrayexpress
Project description:Glioblastoma, the most common and malignant brain tumor, harbors stem-like cells that self-renew and propagate upon serial transplantation. Although they share functional, morphological and developmental similarities to adult brain neural stem cells, stem cell characteristic pathways contributing to glioblastoma stem-like cells have not been consistently determined. Towards this goal we have provided an internally coherent molecular reference that compares adult neural and glioblastoma stem cells cultivated under identical conditions. Genes dysregulated between these populations are correlated with clinical outcome in glioblastoma, and are highly expressed in embryonic and induced pluripotent stem cells. The resource yields a key role for Wnt and a core group of dysregulated pathways. We have verified the contribution to proliferation and sphere formation of Wnt- differentially activated genes through the Wnt inhibitor SFRP1. The glioblastoma and neural stem cell gene-expression and pathway comparative resource provides a powerful new tool for the identification of potential therapeutic targets. 14 samples was analyzed; 5 individual samples of adult neural stem cells and 9 individual samples of glioma stem cells
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Project description:We performed enrichment of nlpI to study its function in Escherichia coli.
2020-02-25 | PXD016825 | Pride
Project description:RNA-seq samples from 3 species across a differentiation from induced pluripotent stem cells to neural progenitor cells were generated to study gene expression evolution. Briefly, previously generated urinary stem cell derived iPSCs of 3 human (Homo sapiens) individuals (3 clones), 1 gorilla (Gorilla gorilla) individual and fibroblast derived cynomolgus macaque (Macaca fascicularis) iPSCs of 2 individuals (4 clones) (Geuder et al. 2021) were differentiated to neural progenitor cells via dual-SMAD inhibition as three-dimensional aggregation culture (Chambers et al. 2009; Ohnuki et al. 2014). Bulk RNA-seq libraries of iPSCs and NPCs were generated using prime-seq protocol (Janjic et al. 2022).
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Project description:Bacterial motility shows a strong evolvable feature depending on the environment. Hyper-motile E. coli could be isolated by evolving non-motile E. coli due to the mutations that enhanced transcriptional expression of the master regulator of the flagellum biosynthesis, FlhDC. These hyper-motile isolates showed reduced growth fitness but with the molecular mechanisms unrevealed. Here we obtained a novel type of hyper-motile isolates by evolving a weakly-motile E. coli K12 strain on the soft agar plates. These isolates carried high accumulated FlhDC proteins and they shared one single point mutation of ClpXV78F. The V78F affected the ATP binding to ClpX via steric repulsive effect and the mutated ClpXP protease lost most of its ability to degraded FlhDC and some other of its known targets. The signal tag of FlhDC for ClpXP recognition was also characterized. Intriguingly, in the hyper-motile strains, the highly enhanced expression of the motility genes was accompanied by the reduced expression of stress resistance genes relating to the reduced fitness of these isolates. Hence, ClpX appeared to be a novel and hot locus during the evolution of bacterial motility and the molecular mechanism of the trade-off between motility and growth was proposed for the first time.
2021-11-25 | PXD023645 | Pride
Project description:BackgroundTerpenoids (isoprenoids) have numerous applications in flavors, fragrances, drugs and biofuels. The number of microbially produced terpenoids is increasing as new biosynthetic pathways are being elucidated. However, efforts to improve terpenoid production in yeast have mostly taken advantage of existing knowledge of the sterol biosynthetic pathway, while many additional factors may affect the output of the engineered system.ResultsAiming to develop a yeast strain that can support high titers of sclareol, a diterpene of great importance for the perfume industry, we sought to identify gene deletions that improved carotenoid, and thus potentially sclareol, production. Using a carotenogenic screen, the best 100 deletion mutants, out of 4,700 mutant strains, were selected to create a subset for further analysis. To identify combinations of deletions that cooperate to further boost production, iterative carotenogenic screens were applied, and each time the top performing gene deletions were further ranked according to the number of genetic and physical interactions known for each specific gene. The gene selected in each round was deleted and the resulting strain was employed in a new round of selection. This approach led to the development of an EG60 derived haploid strain combining six deletions (rox1, dos2, yer134c, vba5, ynr063w and ygr259c) and exhibiting a 40-fold increase in carotenoid and 12-fold increase in sclareol titers, reaching 750 mg/L sclareol in shake flask cultivation.ConclusionUsing an iterative approach, we identified novel combinations of yeast gene deletions that improve carotenoid and sclareol production titers without compromising strain growth and viability. Most of the identified deletions have not previously been implicated in sterol pathway control. Applying the same approach using a different starting point could yield alternative sets of deletions with similar or improved outcome.
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