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Dynamic regulation of tissue fluidity controls skin repair during wound healing [bulk RNA-seq]

ABSTRACT: During wounding healing, different pools of stem cells (SCs) During homeostasis, different compartments of the epidermis are sustained by distinct pools of stem cells (SC) whereas, upon wounding, these different SCs contribute to skin repair. However, how SCs become activated and drive the tissue remodeling essential for skin repair is still poorly understood. Here, by developing a mouse model allowing lineage tracing and basal cell lineage ablation while leaving the basic organization of the skin intact, we monitor SC fate and tissue dynamics during regeneration using confocal and intravital imaging. Analysis of basal cell rearrangements shows dynamic transitions from a solid-like homeostatic state to a fluid-like state allowing tissue remodelling during repair, as predicted by a minimal mathematical modelling of the spatiotemporal dynamics and fate behaviour of the basal cells population. The basal cell layer progressively returns to a solid-like state with re-epithelialization and the restoration of barrier function. Bulk, single-cell RNA and epigenetic profiling of SCs together with functional experiments uncover a common regenerative state regulated by the EGFR/AP1 axis activated during tissue fluidization that is essential for skin SC activation and tissue repair.

ORGANISM(S): Mus musculus

PROVIDER: GSE270771 | GEO | 2024/08/21

REPOSITORIES: GEO

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Dynamic regulation of tissue fluidity controls skin repair during wound healing [ATAC]

Project description:During wounding healing, different pools of stem cells (SCs) During homeostasis, different compartments of the epidermis are sustained by distinct pools of stem cells (SC) whereas, upon wounding, these different SCs contribute to skin repair. However, how SCs become activated and drive the tissue remodeling essential for skin repair is still poorly understood. Here, by developing a mouse model allowing lineage tracing and basal cell lineage ablation while leaving the basic organization of the skin intact, we monitor SC fate and tissue dynamics during regeneration using confocal and intravital imaging. Analysis of basal cell rearrangements shows dynamic transitions from a solid-like homeostatic state to a fluid-like state allowing tissue remodelling during repair, as predicted by a minimal mathematical modelling of the spatiotemporal dynamics and fate behaviour of the basal cells population. The basal cell layer progressively returns to a solid-like state with re-epithelialization and the restoration of barrier function. Bulk, single-cell RNA and epigenetic profiling of SCs together with functional experiments uncover a common regenerative state regulated by the EGFR/AP1 axis activated during tissue fluidization that is essential for skin SC activation and tissue repair.

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Defining stem cell dynamics and migration during wound healing in mouse skin epidermis (D4 post-wound)

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A stem cell-driven lymphoangiogenic switch

Project description:Tissues rely on stem cells (SCs) for homeostasis and wound-repair. SCs reside in specialized microenvironments (niches) whose complexities and roles in orchestrating tissue growth are still unfolding. Here, we identify lymphatic capillaries as critical SC niche components. In skin, lymphatics form intimate networks around the SCs of each hair follicle (HF) during their non-regenerative phase, and remodel upon regeneration. Seeking understanding, we unravel a secretome switch within SCs that controls lymphatic behavior. Resting SCs express Angiopoietin-like 7 (Angptl7), promoting lymphatic drainage. Upon activation, SCs trigger an anti-lympho-angiogenic program, transiently sparking lymphatic dilation and dampened drainage. In mammals, this dynamic aria between SCs and lymphatics is essential for coordinating HFSC behavior and hair regeneration: Upon either depleting lymphatics, silencing Angptl7 or super-activating anti-lympho-angiogenesis, SCs precociously proliferate and HF regeneration becomes asynchronous. In unearthing lymphatic capillaries as a hitherto under-appreciated SC-niche element, we’ve learned how SCs coordinate their activity across a tissue.

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Three-dimensional tissue-engineered human skeletal muscle model of satellite cell quiescence

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Single Cell sequencing of mononuclear cells from regenerating skeletal muscle

Project description:Skeletal muscle stem cells, or satellite cells (SCs), are essential to regenerate and maintain muscle. Quiescent SCs reside in an asymmetric niche between the basal lamina and myofiber membrane. To repair muscle, SCs activate, proliferate, and differentiate, fusing to repair myofibers or reacquiring quiescence to replenish the SC niche. Little is known about when SCs reacquire quiescence during regeneration or the cellular processes that direct SC fate decisions and progression through myogenesis. Single cell sequencing of myogenic cells in regenerating muscle identifies SCs reacquiring quiescence and reveals that non-cell autonomous signaling networks influence SC fate decisions during regeneration. Single cell RNA-sequencing of regenerating skeletal muscle reveals that RBP expression, including numerous neuromuscular disease-associated RBPs, is temporally regulated in skeletal muscle stem cells and correlates to stages of myogenic differentiation. By combining machine learning with RBP engagement scoring, we discover that the neuromuscular disease associated RBP Hnrnpa2b1 is a differentiation-specifying regulator of myogenesis controlling myogenic cell fate transitions during terminal differentiation.

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