Cellular and molecular mechanisms of skin wound healing

Nature Reviews Molecular Cell Biology, Journal Year: 2024, Volume and Issue: 25(8), P. 599 - 616

Published: March 25, 2024

Language: Английский

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Neutrophils and emergency granulopoiesis drive immune suppression and an extreme response endotype during sepsis

Nature Immunology, Journal Year: 2023, Volume and Issue: 24(5), P. 767 - 779

Published: April 24, 2023

Sepsis arises from diverse and incompletely understood dysregulated host response processes following infection that leads to life-threatening organ dysfunction. Here we showed neutrophils emergency granulopoiesis drove a maladaptive during sepsis. We generated whole-blood single-cell multiomic atlas (272,993 cells, n = 39 individuals) of the sepsis immune identified populations immunosuppressive mature immature neutrophils. In co-culture, CD66b+ inhibited proliferation activation CD4+ T cells. Single-cell mapping circulating hematopoietic stem progenitor cells (HSPCs) (29,366 27) indicated altered in patients with These features were enriched patient subset poor outcome specific signature displayed higher frequencies IL1R2+ neutrophils, epigenetic transcriptomic signatures HSPCs STAT3-mediated gene regulation across different infectious etiologies syndromes. Our findings offer potential therapeutic targets opportunities for stratified medicine severe infection.

Language: Английский

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Tumor initiation and early tumorigenesis: molecular mechanisms and interventional targets

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: June 18, 2024

Abstract Tumorigenesis is a multistep process, with oncogenic mutations in normal cell conferring clonal advantage as the initial event. However, despite pervasive somatic and expansion tissues, their transformation into cancer remains rare event, indicating presence of additional driver events for progression to an irreversible, highly heterogeneous, invasive lesion. Recently, researchers are emphasizing mechanisms environmental tumor risk factors epigenetic alterations that profoundly influencing early malignant evolution, independently inducing mutations. Additionally, evolution tumorigenesis reflects multifaceted interplay between cell-intrinsic identities various cell-extrinsic exert selective pressures either restrain uncontrolled proliferation or allow specific clones progress tumors. by which induce both intrinsic cellular competency remodel stress facilitate not fully understood. In this review, we summarize genetic, epigenetic, external events, effects on co-evolution transformed cells ecosystem during initiation evolution. A deeper understanding earliest molecular holds promise translational applications, predicting individuals at high-risk developing strategies intercept transformation.

Language: Английский

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Human embryo implantation

Development, Journal Year: 2023, Volume and Issue: 150(10)

Published: May 15, 2023

Embryo implantation in humans is interstitial, meaning the entire conceptus embeds endometrium before placental trophoblast invades beyond uterine mucosa into underlying inner myometrium. Once implanted, embryo survival pivots on transformation of an anti-inflammatory bed, termed decidua, under homeostatic control natural killer cells. Here, we examine evolutionary context and elaborate remodelling after conception humans. We also discuss interactions between decidualising that regulate interstitial determine fitness. Together, this Review highlights precarious but adaptable nature process.

Language: Английский

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Spatial transcriptomics stratifies psoriatic disease severity by emergent cellular ecosystems

Science Immunology, Journal Year: 2023, Volume and Issue: 8(84)

Published: June 2, 2023

Whereas the cellular and molecular features of human inflammatory skin diseases are well characterized, their tissue context systemic impact remain poorly understood. We thus profiled psoriasis (PsO) as a prototypic immune-mediated condition with high predilection for extracutaneous involvement. Spatial transcriptomics (ST) analyses 25 healthy, active lesion, clinically uninvolved biopsies integration public single-cell data revealed marked differences in immune microniches between healthy inflamed skin. Tissue-scale cartography further identified core disease across all lesions, including emergence an suprabasal epidermal state presence B lymphocytes lesional Both distal nonlesional samples were stratified by severity not disease. This segregation was driven macrophage-, fibroblast-, lymphatic-enriched spatial regions gene signatures associated metabolic dysfunction. Together, these findings suggest that mild severe forms PsO have distinct may profoundly alter composition unaffected sites. In addition, our study provides valuable resource research community to organization

Language: Английский

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Beyond genetics: driving cancer with the tumour microenvironment behind the wheel

Nature reviews. Cancer, Journal Year: 2024, Volume and Issue: 24(4), P. 274 - 286

Published: Feb. 12, 2024

Language: Английский

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Disease modification in inflammatory skin disorders: opportunities and challenges

Nature Reviews Drug Discovery, Journal Year: 2023, Volume and Issue: 22(8), P. 662 - 680

Published: July 13, 2023

Language: Английский

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A temporal perspective for tumor-associated macrophage identities and functions

Cancer Cell, Journal Year: 2024, Volume and Issue: 42(5), P. 747 - 758

Published: April 25, 2024

Language: Английский

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Exploring new perspectives in immunology

Cell, Journal Year: 2024, Volume and Issue: 187(9), P. 2079 - 2094

Published: April 1, 2024

Several conceptual pillars form the foundation of modern immunology, including clonal selection theory, antigen receptor diversity, immune memory, and innate control adaptive immunity. However, some immunological phenomena cannot be explained by current framework. Thus, we still do not know how to design vaccines that would provide long-lasting protective immunity against certain pathogens, why autoimmune responses target antigens others, or response infection sometimes does more harm than good. Understanding these mysteries may require question existing assumptions develop test alternative explanations. Immunology is increasingly at a point when, once again, exploring new perspectives becomes necessity.

Language: Английский

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Dynamic regulation of tissue fluidity controls skin repair during wound healing

Cell, Journal Year: 2024, Volume and Issue: 187(19), P. 5298 - 5315.e19

Published: Aug. 20, 2024

During wound healing, different pools of stem cells (SCs) contribute to skin repair. However, how SCs become activated and drive the tissue remodeling essential for repair is still poorly understood. Here, by developing a mouse model allowing lineage tracing basal cell ablation, we monitor SC fate dynamics during regeneration using confocal intravital imaging. Analysis rearrangements shows dynamic transitions from solid-like homeostatic state fluid-like repair, as predicted minimal mathematical modeling spatiotemporal behavior cells. The layer progressively returns with re-epithelialization. Bulk, single-cell RNA, epigenetic profiling SCs, together functional experiments, uncover common regenerative regulated EGFR/AP1 axis fluidization that activation

Language: Английский

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