Wound memory of epidermal stem cells [scRNAseq_L5]
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE197589 | GEO | 2023/02/02
REPOSITORIES: GEO
Similar Datasets
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.
2023-02-02 | GSE197585 | GEO
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.
2023-02-02 | GSE197583 | GEO
Project description: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)]
2023-02-02 | GSE197586 | GEO
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.
2023-02-02 | GSE197588 | GEO
Project description:Long-term tissue homeostasis is governed by balanced contribution from adult stem cells. We recently identified Lrig1 as a marker of stem cells in mouse epidermis. Here, we show that Lrig1 expressing cells are molecularly and functionally distinct from previously characterized epidermal stem cell populations. During steady state homeostasis, Lrig1 expressing cells are responsible for the maintenance of the uppermost compartment of the pilosebaceous unit known as the infundibulum. Lineage tracing demonstrates that the epidermis is divided into discrete compartments during homeostasis, each maintained by its own resident stem cells. Compartment boundaries are rapidly broken when stem cell progeny are recruited to sites of injury, where they subsequently change behavior according to the environment. Oncogene activation in Lrig1 expressing cells alters proliferation but auxiliary stimuli are required for rapid tumor growth. Our data demonstrate that stem cell niches are compartmentalized according to altering requirements for tissue replenishment.
2013-08-14 | E-MTAB-1606 | biostudies-arrayexpress
Project description:Cancer immunotherapies boost antitumor immunity and improve the survival of cancer patients. V-domain Immunoglobulin Suppressor of T cell Activation (VISTA) is an immune 20 checkpoint target but presents elusive signaling mechanisms. We report a novel VISTA binding partner, Leucine-Rich Repeats and Immunoglobulin Like Domains 1 (LRIG1), which acts as an inhibitory receptor by engaging VISTA and suppressing T cell receptor signaling pathways. Mice with T cell-specific LRIG1 deletion developed superior antitumor T cell responses. Mechanistically, LRIG1-deficient tumor-specific CD8+ cytotoxic T cells (CTLs) exhibited longer 25 persistence due to improved expansion and survival and greater effector function. Sustained tumor control was also associated with a reduction of quiescent CTLs (TCF1+ CD62Lhi PD-1low) and a reciprocal increase in progenitor and memory-like CTLs (TCF1+ PD-1+). In human melanoma, an elevated LRIG1 expression on tumor-infiltrating CD8+ CTLs correlated with resistance to immunotherapies. Taken together, these results delineate the role of LRIG1 as an inhibitory 30 immune checkpoint receptor and propose a rationale for targeting the VISTA/LRIG1 axis for cancer immunotherapy.
2024-10-17 | PXD050084 | Pride
Project description:Multipotent stem cells and their lineage-restricted progeny drive nephron formation within the developing kidney. Validated markers of these early stem/progenitor populations are essential for deciphering their in vivo function and for evaluating their clinical potential for treating adult kidney disease. Here, we document expression of the adult stem cell marker Lgr5 in the developing kidney and assess the stem/progenitor identity of Lgr5+ve cells via in vivo lineage tracing. The appearance and localization of Lgr5+ve cells coincided with that of the S-shaped body around E14. Lgr5 expression remained restricted to cell clusters within developing nephrons in the cortex until P7, when expression was permanently silenced. In vivo lineage tracing identified Lgr5 as a marker of a novel progenitor population within nascent nephrons dedicated to generating the thick ascending limb of Henle's loop and distal convoluted tubule. The Lgr5 surface marker and experimental models described here will be invaluable for deciphering the contribution of early nephron stem cells to developmental defects and for isolating human nephron progenitors as a prerequisite to evaluating their therapeutic potential. Metanephric kidneys of timed pregnancies of ~14 days of gestation were harvested and cultured for ~10 days. Lgr5-EGFP-Ires-CreERT2-positive embryonic kidneys were identified by fluorescence microscopy and enzymatically digested to a single cell solution. GFPhi and GFPneg cells were sorted by flow cytometry (MoFlo; Dako). RNA, isolated using RNeasy (Qiagen), was analyzed using the Affymetrix platform.
2012-09-04 | E-GEOD-39881 | biostudies-arrayexpress
Project description:Studying the transcriptomic response of different epidermal stem cell populations to wounding has been difficult due to intermixing of wound healing and homeostastic cells from different stem cell pools in bulk-cell sequencing setups. Here, we circumvent those problems by using a single-cell sequencing approach. We randomly sequenced the traced progeny of either Lgr5 or Lgr6 stem cells isolated from wounded or unwounded skin 0 day (control), 1 d, 4 d, 7 d, 10 d or more than 1 month after wounding. We then identified Lgr5 or Lgr6 wound cells using a computational approach. Wound cells were defined by using a negative binominal Naïve Bayes classifier with 0-day control cells (unwounded mice) as reference. Wound cell populations were defined by clustering wound cells in t-SNE space using k-means clustering.
2018-04-01 | E-MTAB-6583 | biostudies-arrayexpress
Project description:Sweat glands are abundant glands of our body and essential for thermoregulation. Like mammary glands, they originate from epidermal progenitors. However, they display few signs of cellular turnover, and whether they have stem cells and tissue regenerative capacity remain largely unexplored. Here we address these issues. Using lineage-tracing, we identify multipotent progenitors in sweat duct that transition to unipotency after developing the sweat gland. In characterizing four adult stem cell populations of glandular skin, we show that they display distinct regenerative capabilities and remain unipotent when healing epidermal, myoepithelial-specific and luminal-specific injuries. We devise purification schemes, isolate and transcriptionally profile progenitors. Exploiting molecular differences between sweat and mammary glands, we show that only some progenitors regain multipotency to produce de novo ductal and glandular structures, but that these can retain their identity even within certain foreign microenvironments. Our findings provide new concepts about glandular stem cells and sweat gland biology. 10 samples from mouse paw pads were analyzed
2013-01-02 | E-GEOD-37274 | biostudies-arrayexpress
Project description:Transcriptome profiling using Affymetrix GeneChip arrays was performed on sorted populations of Lgr5-expressing mouse ovarian surface epithelium. The ovary surface epithelium (OSE) undergoes ovulatory tear-and-remodelling throughout life. Resident stem cells drive such tissue homeostasis in many adult epithelia, but their existence in the ovary has yet to be definitively proven. Lgr5 marks stem cells in multiple epithelia. Here we use reporter mice and Single Molecule Florescent-in-Situ-Hybridization (FISH) to document candidate Lgr5+ stem cells within the mouse ovary and associated structures. Lgr5 is broadly expressed during ovary organogenesis, but becomes limited to the OSE in early neonate life. In adults, Lgr5 expression is predominantly restricted to proliferative regions of the OSE and fimbria- mesovarian junction. Using conditional in vivo lineage tracing we identify embryonic and early neonate Lgr5+ populations as stem/progenitor cells contributing to the development of adult OSE and granulosa cell lineages, as well as the epithelia of the mesovarian and oviduct including its distal opening, fimbria. Long-term lineage tracing reveals that adult OSE-resident Lgr5+ populations contribute to epithelial homeostasis and OSE regenerative repair in vivo. Thus, Lgr5 is a marker of stem/progenitor cells of the ovary and tubal epithelia. Ovarian surface epithelium from pooled batches of Lgr5-eGFP-CreERT2 mice (n=8, per array) were sorted for cells expressing either high or low EGFP. Total RNA from three technical replicates per sorted population (Lgr5-high or Lgr5-low) was extracted with the RNeasy Micro Kit (QIAGEN), DNaseI-treated, and amplified with the Ovation Pico WTA V2 (NuGEN Technologies). Single-stranded cDNA amplification products were purified using QIAquick PCR Purification Kit (QIAGEN). cDNA was biotinylated using the Encore Biotin Module (NuGEN Technologies). Biotiylated cDNA was hybridized to Affymetrix Mouse Genechip ST 2.0 expression arrays.
2013-12-04 | E-GEOD-52925 | biostudies-arrayexpress