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Gonzales, K. A. U., Polak, L., & Matos, I. (2021). Stem cells expand potency and alter tissue fitness by accumulating diverse epigenetic memories. Science, 374(6571), eabh2444. Added by: Dr. Enrique Feoli (16/04/2022, 12:11) Last edited by: Dr. Enrique Feoli (25/12/2023, 11:24) |
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| Resource type: Journal Article DOI: 10.1126/science.abh2444 BibTeX citation key: Gonzales2021 View all bibliographic details  |
Categories: BioAcyl Corp Subcategories: Inflammatory memory Creators: Gonzales, Matos, Polak Collection: Science |
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| Abstract |
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Immune and tissue stem cells retain an epigenetic memory of inflammation that intensifies sensitivity to future encounters. We investigated whether and to what consequence stem cells possess and accumulate memories of diverse experiences. Monitoring a choreographed response to wounds, we found that as hair follicle stem cells leave their niche, migrate to repair damaged epidermis, and take up long-term foreign residence there, they accumulate long-lasting epigenetic memories of each experience, culminating in post-repair epigenetic adaptations that sustain the epidermal transcriptional program and surface barrier. Each memory is distinct, separable, and has its own physiological impact, collectively endowing these stem cells with heightened regenerative ability to heal wounds and broadening their tissue-regenerating tasks relative to their naïve counterparts.
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| Notes |
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Stem cells accumulate epigenetic memories of their past experiences.
As hair follicle stem cells mobilize to repair wounded skin epidermis and take up residence as epidermal stem cells, they temporally change chromatin states. Each environmental encounter leaves a discrete long-lasting epigenetic memory, enabling these immigrant stem cells to perform their new tasks while also heightening future responses to injury, inflammation, and hair regeneration.
By denuding the epidermis, we coaxed underlying HFSCs to be the primary responders to re-epithelialization. This creates a long-term, self-renewing epidermis that is largely HF-derived. The fate-changed epidermal stem cells (EpdSCs) were indistinguishable from native unwounded EpdSCs in homeostatic function and transcriptome. However, assay for transposase-accessible chromatin using sequencing (ATAC-seq) revealed many loci with increased accessibility. Open chromatin domains distinguishing HF-derived from native EpdSCs came in three forms: (i) domains that increased accessibility only during adaptation to the new epidermal niche (compensatory adaptation), (ii) domains that opened during the wound response (memory of wound), and (iii) domains that were already open in quiescent HFSCs (memory of niche origin). Each enduring epigenetic memory had its own consequence. Compensatory adaptation domains enabled key differentiation and immune defense transcripts necessary for maintaining the skin’s barrier to be expressed at native levels. Wound memory domains primed genes involved in inflammation, cytoskeletal reorganization, and migration to be robustly induced upon secondary wounds, thus accelerating healing. Memory of niche origin domains were associated with genes involved in HFSC fate and WNT signaling, imparting plasticity to revert to the HF fate given the right environmental cues. Finally, these memories, although cumulative, were distinct, separable, and dependent on past experiences. Thus, EpdSCs that repaired epidermal injuries exhibited a wound memory but lacked memories of HF niche origin and epidermal compensatory adaptation.
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