Skin cell heterogeneity and dynamics during morphogenesis, tissue homeostasis, and regeneration
Author: Jacob, Tina
Date: 2021-04-23
Location: Eva & Georg Klein Lecture Hall, Biomedicum, Solnavägen 9, Karolinska Institutet, Campus Solna, Stockholm
Time: 09.30
Department: Inst för biovetenskaper och näringslära / Dept of Biosciences and Nutrition
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Thesis (4.417Mb)
Abstract
Skin is our protective barrier against various environmental harms. For the skin to fulfill its crucial function, it relies on multiple cell types working in concert; but most importantly it relies on skin-resident epithelial stem cells. These cells ensure an intact barrier through constant replacement of the epidermis and they ensure proper hair production through cyclical regeneration of hair follicles. This combination of constant and cyclical renewal within one tissue makes skin a prime model system for the study of adult tissue stem cells. The overall aim of this thesis was to transcriptionally dissect this well-established model system in a systematic and unbiased way. The majority of data presented in this thesis is based on the combination of single-cell RNA sequencing and in situ stainings of mRNA. This combination allows us to appreciate the genome-wide transcriptional heterogeneity while still being able to place the identified cell populations in their spatial tissue context.
In Paper I, the first whole-transcriptome study of skin at the single-cell level, we examined the vectors describing cellular heterogeneity within the epidermal compartment of mouse skin during its resting stage (telogen). In Paper II, we expanded on this analysis by including full-thickness skin during rest (telogen) and growth (anagen). This allowed for an unbiased census of all major cell types contained in the skin, and it furthermore enabled us to study how skin achieves and accommodates hair growth. In Paper III, we studied the role of dermal fibroblasts in early embryonic skin development. We uncovered unexpected heterogeneity among embryonic fibroblasts and explored their supportive functions for skin maturation. Moreover, we identified novel keratinocyte subpopulations and closely analyzed epidermal fate decisions. In Paper IV, we monitored transcriptional adaptations of two distinct epidermal stem cell populations during their contribution to wound healing. This allowed us to answer fundamental questions about stem cell plasticity and the dynamics of cell adaptations following injury. In sum, this thesis uncovers the dynamic and heterogeneous nature of mouse skin during adult tissue homeostasis, embryonic development, and tissue regeneration after injury. Most importantly, we provide new insights into how stem cell identity is shaped and how developmental as well as regenerative processes are orchestrated.
In Paper I, the first whole-transcriptome study of skin at the single-cell level, we examined the vectors describing cellular heterogeneity within the epidermal compartment of mouse skin during its resting stage (telogen). In Paper II, we expanded on this analysis by including full-thickness skin during rest (telogen) and growth (anagen). This allowed for an unbiased census of all major cell types contained in the skin, and it furthermore enabled us to study how skin achieves and accommodates hair growth. In Paper III, we studied the role of dermal fibroblasts in early embryonic skin development. We uncovered unexpected heterogeneity among embryonic fibroblasts and explored their supportive functions for skin maturation. Moreover, we identified novel keratinocyte subpopulations and closely analyzed epidermal fate decisions. In Paper IV, we monitored transcriptional adaptations of two distinct epidermal stem cell populations during their contribution to wound healing. This allowed us to answer fundamental questions about stem cell plasticity and the dynamics of cell adaptations following injury. In sum, this thesis uncovers the dynamic and heterogeneous nature of mouse skin during adult tissue homeostasis, embryonic development, and tissue regeneration after injury. Most importantly, we provide new insights into how stem cell identity is shaped and how developmental as well as regenerative processes are orchestrated.
List of papers:
I. Simon Joost, Amit Zeisel, Tina Jacob, Xiaoyan Sun, Gioele La Manno, Peter Lönnerberg, Sten Linnarsson, and Maria Kasper. Single-cell transcriptomics reveals that differentiation and spatial signatures shape epidermal and hair follicle heterogeneity. Cell Systems. 3, 3 (2016): 221-237.
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II. Simon Joost*, Karl Annusver*, Tina Jacob, Xiaoyan Sun, Tim Dalessandri, Unnikrishnan Sivan, Inês Sequeira, Rickard Sandberg, and Maria Kasper. The molecular anatomy of mouse skin during hair growth and rest. Cell Stem Cell. 26, 3 (2020): 441-457. *These authors have contributed equally.
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III. Tina Jacob, Karl Annusver, Paulo Czarnewski, Tim Dalessandri, Maria Eleni Kastriti, Chiara Levra Levron, Beate Lichtenberger, Giacomo Donati, Åsa Björklund, and Maria Kasper. Fibroblasts govern the molecular design of early skin development. [Manuscript]
IV. Simon Joost, Tina Jacob, Xiaoyan Sun, Karl Annusver, Gioele La Manno, Inderpreet Sur, and Maria Kasper. Single-cell transcriptomics of traced epidermal and hair follicle stem cells reveals rapid adaptations during wound healing. Cell Reports. 25, 3 (2018): 585-597.
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I. Simon Joost, Amit Zeisel, Tina Jacob, Xiaoyan Sun, Gioele La Manno, Peter Lönnerberg, Sten Linnarsson, and Maria Kasper. Single-cell transcriptomics reveals that differentiation and spatial signatures shape epidermal and hair follicle heterogeneity. Cell Systems. 3, 3 (2016): 221-237.
Fulltext (DOI)
Pubmed
View record in Web of Science®
II. Simon Joost*, Karl Annusver*, Tina Jacob, Xiaoyan Sun, Tim Dalessandri, Unnikrishnan Sivan, Inês Sequeira, Rickard Sandberg, and Maria Kasper. The molecular anatomy of mouse skin during hair growth and rest. Cell Stem Cell. 26, 3 (2020): 441-457. *These authors have contributed equally.
Fulltext (DOI)
Pubmed
View record in Web of Science®
III. Tina Jacob, Karl Annusver, Paulo Czarnewski, Tim Dalessandri, Maria Eleni Kastriti, Chiara Levra Levron, Beate Lichtenberger, Giacomo Donati, Åsa Björklund, and Maria Kasper. Fibroblasts govern the molecular design of early skin development. [Manuscript]
IV. Simon Joost, Tina Jacob, Xiaoyan Sun, Karl Annusver, Gioele La Manno, Inderpreet Sur, and Maria Kasper. Single-cell transcriptomics of traced epidermal and hair follicle stem cells reveals rapid adaptations during wound healing. Cell Reports. 25, 3 (2018): 585-597.
Fulltext (DOI)
Pubmed
View record in Web of Science®
Institution: Karolinska Institutet
Supervisor: Kasper, Maria
Co-supervisor: Toftgård, Rune; Gerling, Marco
Issue date: 2021-03-31
Rights:
Publication year: 2021
ISBN: 978-91-8016-153-4
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