Wound memory of epidermal stem cells [scRNAseq L1 PRT]
Ontology highlight
ABSTRACT: Wound priming in epidermal Lrig1 stem cell progeny leads to a more efficient response to future injuries. To identify a key epigenetic factor of this cellular adaptation, we performed an epigenetic drug screening in Lrig1 genetically labled mice. Pre-treatment with PRT4165 lead to a more efficient wound closure. To understand if PRT4165 was able to recapitulate wound priming, we performed single cell RNA-seq transcriptome profiling of epidermal Lrig1 stem cell progenies from PRT4165-treated or untreated murine skin. [PRT4165is an inhibitor of the enzymatic activity of Ring1a/Ring1b, component of the Polycomb repressive complexes 1 (PRC1), responsible for the monoubiquitination of lysin 119 on histone H2A (H2AK119ub)]
Project description:Wound priming in epidermal Lrig1 stem cell progeny leads to a more efficient response to future injuries. To understand if primed progenitors maintain during aging the transcriptional program acquired during wound healing in young age, we performed single cell RNA-Seq of Lrig1 stem cell progeny 40 weeks after injury.
Project description:Trained wound-memory in epidermal cells elicits a more efficient response to future injuries, but the full spectrum of their adaptive responses and the contribution of cell lineage subsets is unknown. We performed single cell RNA-Seq of Lrig1 and Lgr5 stem cell progenies in the context of two consecutive skin injuries to deeply characterise lineage specific adaptation mecanisms.
Project description:Trained wound-memory in epidermal cells elicits a more efficient response to future injuries, but the full spectrum of their adaptive responses and the contribution of cell lineage subsets is unknown. We performed mini bulk RNA-Seq of Lrig1 and Lgr5 stem cell progenies in the context of two consecutive skin injuries to deeply characterise lineage specific adaptation mecanisms.
Project description:Trained wound-memory in epidermal cells elicits a more efficient response to future injuries, but the full spectrum of their adaptive responses and the contribution of cell lineage subsets is unknown. We performed single cell RNA-Seq of Lrig1 and Lgr5 stem cell progenies in the context of two consecutive skin injuries to deeply characterise lineage specific adaptation mecanisms.
Project description:These data include RNA Seq data generated from wild type and Ring1a Ring1b dKO ISCs from Lgr5Gfp-CreERT2, Lgr5Gfp-CreERT2 Ring1a-/- Ring1bf/f, Lgr5Gfp-CreERT2-Ctnnb1-ex3 and Lgr5Gfp-CreERT2 Ring1a-/- Ring1bf/f-Ctnnb1-ex3 mice. Total RNA extracted from sorted wild type and Ring1a Ring1b dKO ISCs.
Project description:These data include RNA Seq data generated from wild type and Ring1a Ring1b dKO Villi from Rosa26-CreERT2 Cdkn2a-/- and Rosa26-CreERT2 Cdkn2a-/- Ring1a-/- Ring1bf/f mice. Total RNA extracted from wild type and Ring1a Ring1b dKO Villi.
Project description:These data include RNA Seq data generated from Ring1b wild type and Ring1b KO Ring1a-/- Cdkn2a-/- Lin- HSC cells non-transduced or transduced with MLL-AF9, HOXA9 and PML-RARa. Total RNA extracted from Ring1b wild type and Ring1b KO Ring1a-/- Cdkn2a-/- Lin- HSC cells non-transduced or transduced with MLL-AF9, HOXA9 and PML-RARa.
Project description:These data include RNA Seq data generated from wild type and Ring1a Ring1b dKO ISCs from Lgr5Gfp-CreERT2, Lgr5Gfp-CreERT2 Ring1a-/- Ring1bf/f, Lgr5Gfp-CreERT2-Ctnnb1-ex3 and Lgr5Gfp-CreERT2 Ring1a-/- Ring1bf/f-Ctnnb1-ex3 mice.
Project description:Polycomb proteins are epigenetic regulators important for cell fate decision and maintenance. Here we show that PCGF1, one of components of Polycomb repressive complex (PRC) 1 is important for the differentiation of hematopoietic stem/progenitor cells (HSPCs) towards lymphoid lineage. The deletion of Pcgf1 in HSPCs lead to severe defects in B cell development with an expansion of myeloid progenitors. The blockade of B cell differentiation occurred at the lymphoid-primed multipotent progenitor (LMPP) stage. Chromatin immunoprecipitation followed by DNA sequencing analysis of normal LMPP-like cells demonstrated that PCGF1 colocalized with RING1A/B and PRC2. Upon deletion of Pcgf1, we found dramatic decline of H3K27me3 levels, resulting in de-repression of target genes. Strikingly, the occupancy of RING1A/B, PRC2 and monoubiquitination of histone H2A at lysin 119 on the target loci was not affected. These results demonstrate that the PCGF1 safeguards the immune system development by directly regulating the PRC2-mediated H3K27me3 levels.
Project description:Polycomb proteins are epigenetic regulators important for cell fate decision and maintenance. Here we show that PCGF1, one of components of Polycomb repressive complex (PRC) 1 is important for the differentiation of hematopoietic stem/progenitor cells (HSPCs) towards lymphoid lineage. The deletion of Pcgf1 in HSPCs lead to severe defects in B cell development with an expansion of myeloid progenitors. The blockade of B cell differentiation occurred at the lymphoid-primed multipotent progenitor (LMPP) stage. Chromatin immunoprecipitation followed by DNA sequencing analysis of normal LMPP-like cells demonstrated that PCGF1 colocalized with RING1A/B and PRC2. Upon deletion of Pcgf1, we found dramatic decline of H3K27me3 levels, resulting in de-repression of target genes. Strikingly, the occupancy of RING1A/B, PRC2 and monoubiquitination of histone H2A at lysin 119 on the target loci was not affected. These results demonstrate that the PCGF1 safeguards the immune system development by directly regulating the PRC2-mediated H3K27me3 levels.