Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Epidermal overexpression of âNLef1 leads to deregulation of epidermal stem cell fate.

ABSTRACT: In adult K14ÎNLef1 mouse, the overexpression of âNLef1, a B-catenin dominat negative, in basal keratinocytes leads to the conversion of hair follicles into multilayered epithelial cysts and ectopic sebaceous gland. To uncover in vivo changes in gene expression associated to âNLef1 activity, we compared the expression profiles of unfractionated keratinocytes in wild type and K14ÎNLef1 transgenic mice. Cells were collected from 9.5 week old mice, when the hair follicle are in the resting (telogen) phase of the hair growth cycle. At this stage the âNLef1 phenotype is not yet evident enabling us to detect early molecular events. We compared the expression profiles of unfractionated keratinocytes in wild type and K14ÎNLef1 transgenic 9.5 week old mice. Three biological replicates for each cell population were analyzed.

ORGANISM(S): Mus musculus

SUBMITTER: Giacomo Donati

PROVIDER: E-GEOD-62603 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Wounding induces dedifferentiation of epidermal Gata6<sup>+</sup> cells and acquisition of stem cell properties.

Donati Giacomo G Rognoni Emanuel E Hiratsuka Toru T Liakath-Ali Kifayathullah K Hoste Esther E Kar Gozde G Kayikci Melis M Russell Roslin R Kretzschmar Kai K Mulder Klaas W KW Teichmann Sarah A SA Watt Fiona M FM

Nature cell biology 20170515 6

The epidermis is maintained by multiple stem cell populations whose progeny differentiate along diverse, and spatially distinct, lineages. Here we show that the transcription factor Gata6 controls the identity of the previously uncharacterized sebaceous duct (SD) lineage and identify the Gata6 downstream transcription factor network that specifies a lineage switch between sebocytes and SD cells. During wound healing differentiated Gata6<sup>+</sup> cells migrate from the SD into the interfollicu ...[more]

PMID: 28504705

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Project description:Hair follicle formation depends on reciprocal epidermal-dermal interactions and occurs during skin development, but not in adult life. This suggests that the properties of dermal fibroblasts change during postnatal development. To examine this, we used a PdgfraEGFP mouse line to isolate GFP-positive fibroblasts from neonatal skin, adult telogen and anagen skin and adult skin in which ectopic hair follicles had been induced (EF skin) by transgenic epidermal activation of beta-catenin. We also isolated epidermal cells from each mouse. The gene expression profile of EF epidermis was most similar to that of anagen epidermis, consistent with activation of beta-catenin signalling. In contrast, adult dermis with ectopic hair follicles more closely resembled neonatal dermis than adult telogen or anagen dermis. In particular, genes associated with mitosis were upregulated and extracellular matrix-associated genes were downregulated in neonatal and EF fibroblasts. We confirmed that sustained epidermal beta-catenin activation stimulated fibroblasts to proliferate to reach the high cell density of neonatal skin. In addition, the extracellular matrix was comprehensively remodelled, with mature collagen being replaced by collagen subtypes normally present only in developing skin. The changes in proliferation and extracellular matrix composition originated from a specific subpopulation of fibroblasts located beneath the sebaceous gland. Our results show that adult dermis is an unexpectedly plastic tissue that can be reprogrammed to acquire the molecular, cellular and structural characteristics of neonatal dermis in response to cues from the overlying epidermis. We have isolated the following populations of cells from mouse back skin by flow cytometry: 1A) GFP+ WT neonatal dermal fibroblasts, 1B) ItgA6+ WT neonatal epidermal keratinocytes, 2A) GFP+ WT telogen dermal fibroblasts, 2B) ItgA6+ WT telogen epidermal keratinocytes, 3A) GFP+ D2 transient activation (anagen) dermal fibroblasts, 3B) ItgA6+ D2 transient activation (anagen) epidermal keratinocytes, 4A) GFP+ D2 sustained activation (ectopic follicles) dermal fibroblasts, 4B) ItgA6+ D2 sustained activation (ectopic follicles) epidermal keratinocytes

Project description:The epithelial lining of the small intestine is continuously renewed from a small number of stem cells including Lgr5 expressing crypt base cells that have been shown to be a rapidly cycling stem cell population in homeostasis. Alternative markers of intestinal stem cells have variously identified populations as rapidly cycling or quiescent with proposed roles for the latter as a parallel or reserve stem cell population. However, the exact nature of quiescent crypt cells remains unknown. Here by applying novel mouse models that permit their isolation and characterisation as label-retaining cells (LRCs), and for the first time performing lineage tracing from them, we show quiescent cells to be committed secretory precursors that are capable of recall to the stem cell state. We reveal LRCs to be a small subset of the rapidly cycling Lgr5 expressing population committed along the Paneth-enteroendocrine lineage. Significantly, after injury and subsequent regeneration they are clonogenic, as shown by both lineage tracing and organoid growth demonstrating that they can be recalled to the stem cell pool. These findings in establishing quiescent cells as an effective clonogenic reserve during injury provides a motivation for investigating their role in the maintenance of cancer growth following adjuvant treatment. Six age and sex (female) matched Cyp1a1-H2B-YFP mice ten days post βNF induction were used comparing three cell populations from each. Following epithelial isolation, single cell preparation and staining with anti-CD24 anitbody and UEA-1 lectin, 30,000 cells were flow sorted for each population: Paneth cells (Paneth) were defined as CD24+/UEA+, YFP-LRCs (YFPpos) as CD24+/UEA-/YFP+ and LCCs (YFPneg) as CD24+/UEA-/YFP-. Microarray expression comparison was then performed to identify unique markers of each population. RNA amplification and hybridisation was performed at the Paterson Institute, Manchester, UK, Microarray Facility using Nugen Ovation Pico WTA System for amplification and then hybridisation to a Mouse Exon 1.0 ST Array. Arrays were scanned using an Affymetrix GeneChip scanner 3000 running GCOS software.

Dataset Information

Epidermal overexpression of âNLef1 leads to deregulation of epidermal stem cell fate.

Publications

Wounding induces dedifferentiation of epidermal Gata6<sup>+</sup> cells and acquisition of stem cell properties.

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Epidermal overexpression of âNLef1 leads to deregulation of epidermal stem cell fate.