자료유형  

 학위논문

Control Number  

0016931433

International Standard Book Number  

9798379781491

Dewey Decimal Classification Number  

574

Main Entry-Personal Name  

Justynski, Olivia.

Publication, Distribution, etc. (Imprint  

[S.l.] : Yale University., 2023

Publication, Distribution, etc. (Imprint  

Ann Arbor : ProQuest Dissertations & Theses, 2023

Physical Description  

1 online resource(105 p.)

General Note  

Source: Dissertations Abstracts International, Volume: 85-01, Section: B.

General Note  

Advisor: Horsley, Valerie.

Dissertation Note  

Thesis (Ph.D.)--Yale University, 2023.

Restrictions on Access Note  

This item must not be sold to any third party vendors.

Summary, Etc.  

요약The skin is an essential barrier against the outside world, and must withstand constant exposure to damage from the environment. When this barrier is broken, it must be repaired quickly and effectively in order to prevent infection and restore function. The skin's ability to heal wounds is vital for human health, and insufficient wound treatment is a major clinical problem, contributing to decreased quality of life and increased healthcare costs for many patients due to chronic or non-healing wounds. The complex process of wound healing involves the coordination of many cell types and signals, which were here investigated using single-cell RNA sequencing to provide a map of the cellular dynamics during early inflammation in mouse skin wounds. This dataset showed that cell death, particularly programmed cell death (apoptosis), is widespread between 24 and 48 hours after injury, resulting in changed cell populations over time. Apoptosis and clearance of apoptotic cells via efferocytosis are evolutionarily conserved processes that drive tissue repair. However, the mechanisms by which recognition and clearance of apoptotic cells regulate repair are not fully understood. In skin wounds, it was found that apoptotic pathways and efferocytosis receptors were elevated in fibroblasts and immune cells during inflammation. Despite the prevalence of cell death, dead cells were not widely observed in skin wounds, due to the efficient clearance of these dead cells by efferocytosis. One receptor important for this process, Axl, was highly upregulated after injury and expressed by both dendritic cells and fibroblasts. Axl expression was upregulated by TLR3 signaling, but could also be initiated by TLR3-independent mechanisms, indicating multiple redundant pathways for Axl function. Finally, antibody inhibition experiments in vivo in mice revealed that Axl signaling is necessary for effective wound repair, but is dispensable for efferocytosis. In particular, Axl was required for proper revascularization and fibroblast repopulation in the wound bed during the proliferative stage of healing. These data highlight the distinct mechanisms by which apoptotic cell detection, particularly via the receptor Axl, coordinates tissue repair, as well as providing potential therapeutic targets for chronic wounds.

Subject Added Entry-Topical Term  

Biology.

Subject Added Entry-Topical Term  

Cellular biology.

Subject Added Entry-Topical Term  

Molecular biology.

Subject Added Entry-Topical Term  

Immunology.

Index Term-Uncontrolled  

Apoptosis

Index Term-Uncontrolled  

Axl

Index Term-Uncontrolled  

Efferocytosis

Index Term-Uncontrolled  

Wound healing

Index Term-Uncontrolled  

Apoptotic cells

Index Term-Uncontrolled  

TLR3 signaling

Added Entry-Corporate Name  

Yale University Molecular Cellular and Developmental Biology

Host Item Entry  

Dissertations Abstracts International. 85-01B.

Host Item Entry  

Dissertation Abstract International

Electronic Location and Access  

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Control Number  

joongbu:642291