Wound memory of epidermal stem cells [bulk RNA-seq]
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE197583 | GEO | 2023/02/02
REPOSITORIES: GEO
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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.
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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.
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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)]
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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.
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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.
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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.
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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
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