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1. LYVE-1+ macrophages form a collaborative CCR5-dependent perivascular niche that influences chemotherapy responses in murine breast cancer

Author

Anstee, Joanne E., Feehan, Karen T., Opzoomer, James W., Dean, Isaac, Muller, Henrike P., Bahri, Meriem, Cheung, Tik Shing, Liakath-Ali, Kifayathullah, Liu, Ziyan, Choy, Desmond, Caron, Jonathan, Sosnowska, Dominika, Beatson, Richard, Muliaditan, Tamara, An, Zhengwen, Gillett, Cheryl E., Lan, Guocheng, Zou, Xiangang, Watt, Fiona M., Ng, Tony, Burchell, Joy M., Kordasti, Shahram, Withers, David R., Lawrence, Toby, and Arnold, James N.

Published
2023
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10. LYVE-1+ macrophages form a collaborative CCR5-dependent perivascular niche that influences chemotherapy responses in murine breast cancer.

Author

Anstee, Joanne E, Feehan, Karen T, Opzoomer, James W, Dean, Isaac, Muller, Henrike P, Bahri, Meriem, Cheung, Tik Shing, Liakath-Ali, Kifayathullah, Liu, Ziyan, Choy, Desmond, Caron, Jonathan, Sosnowska, Dominika, Beatson, Richard, Muliaditan, Tamara, An, Zhengwen, Gillett, Cheryl E, Lan, Guocheng, Zou, Xiangang, Watt, Fiona M, Ng, Tony, Burchell, Joy M, Kordasti, Shahram, Withers, David R, Lawrence, Toby, Arnold, James N, Anstee, Joanne E, Feehan, Karen T, Opzoomer, James W, Dean, Isaac, Muller, Henrike P, Bahri, Meriem, Cheung, Tik Shing, Liakath-Ali, Kifayathullah, Liu, Ziyan, Choy, Desmond, Caron, Jonathan, Sosnowska, Dominika, Beatson, Richard, Muliaditan, Tamara, An, Zhengwen, Gillett, Cheryl E, Lan, Guocheng, Zou, Xiangang, Watt, Fiona M, Ng, Tony, Burchell, Joy M, Kordasti, Shahram, Withers, David R, Lawrence, Toby, and Arnold, James N

Abstract

Tumor-associated macrophages (TAMs) are a heterogeneous population of cells that facilitate cancer progression. However, our knowledge of the niches of individual TAM subsets and their development and function remain incomplete. Here, we describe a population of lymphatic vessel endothelial hyaluronan receptor-1 (LYVE-1)-expressing TAMs, which form coordinated multi-cellular "nest" structures that are heterogeneously distributed proximal to vasculature in tumors of a spontaneous murine model of breast cancer. We demonstrate that LYVE-1 + TAMs develop in response to IL-6, which induces their expression of the immune-suppressive enzyme heme oxygenase-1 and promotes a CCR5-dependent signaling axis, which guides their nest formation. Blocking the development of LYVE-1 + TAMs or their nest structures, using gene-targeted mice, results in an increase in CD8 + T cell recruitment to the tumor and enhanced response to chemotherapy. This study highlights an unappreciated collaboration of a TAM subset to form a coordinated niche linked to immune exclusion and resistance to anti-cancer therapy.

Published
2023

11. LYVE-1+ macrophages form a collaborative CCR5-dependent perivascular niche that influences chemotherapy responses in murine breast cancer.

Author

Afd Pharmacology, Pharmacology, Anstee, Joanne E, Feehan, Karen T, Opzoomer, James W, Dean, Isaac, Muller, Henrike P, Bahri, Meriem, Cheung, Tik Shing, Liakath-Ali, Kifayathullah, Liu, Ziyan, Choy, Desmond, Caron, Jonathan, Sosnowska, Dominika, Beatson, Richard, Muliaditan, Tamara, An, Zhengwen, Gillett, Cheryl E, Lan, Guocheng, Zou, Xiangang, Watt, Fiona M, Ng, Tony, Burchell, Joy M, Kordasti, Shahram, Withers, David R, Lawrence, Toby, Arnold, James N, Afd Pharmacology, Pharmacology, Anstee, Joanne E, Feehan, Karen T, Opzoomer, James W, Dean, Isaac, Muller, Henrike P, Bahri, Meriem, Cheung, Tik Shing, Liakath-Ali, Kifayathullah, Liu, Ziyan, Choy, Desmond, Caron, Jonathan, Sosnowska, Dominika, Beatson, Richard, Muliaditan, Tamara, An, Zhengwen, Gillett, Cheryl E, Lan, Guocheng, Zou, Xiangang, Watt, Fiona M, Ng, Tony, Burchell, Joy M, Kordasti, Shahram, Withers, David R, Lawrence, Toby, and Arnold, James N

Published
2023

13. Myosin 10 is involved in murine pigmentation

Author

Liakath-Ali, Kifayathullah, Vancollie, Valerie E, Sequeira, Inês, Lelliott, Christopher J, Watt, Fiona M, Liakath-Ali, Kifayathullah [0000-0001-9047-7424], Vancollie, Valerie E [0000-0003-1547-1975], Lelliott, Christopher J [0000-0001-8087-4530], Watt, Fiona M [0000-0001-9151-5154], and Apollo - University of Cambridge Repository

Subjects
Male, Mice, Knockout, integumentary system, Pigmentation, Hair follicles, Myosin, Gene Expression, Penetrance, Skin Pigmentation, myosin, Myosins, Mice, Inbred C57BL, melanocytes, Mice, Melanocytes, Animals, pigmentation, Female, Syndactyly, Hair Color, Hair Follicle, Pigmentation Disorders, Alleles, hair follicles
Abstract

Myosins are molecular motors that are well known for their role in cell movement and contractile functions. Although extensively studied in muscle physiology, little is known about the function of myosins in mammalian skin. As part of the Sanger Institute Mouse Genetics Project, we have identified a role for Myo10 in pigmentation, with a phenotype unlike those of Myo5a or Myo7a. Adult mice homozygous for a disrupted Myo10 allele on a C57BL/6N background displayed a high degree of penetrance for white patches on their abdomen and dorsal surface. Forepaw syndactyly and hind paw syndactyly were also observed in these mice. Tail epidermal wholemounts showed a complete lack of melanocytes in the hair follicles and interfollicular epidermis. Myo10 has previously been implicated in human pigmentation. Our current study reveals involvement of Myo10 in murine skin pigmentation.

Published
2021
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14. Perivascular macrophages collaborate to facilitate chemotherapy resistance in cancer

Author

Anstee, Joanne E., primary, Opzoomer, James W., additional, Dean, Isaac, additional, Muller, Henrike P., additional, Bahri, Meriem, additional, Liakath-Ali, Kifayathullah, additional, Liu, Ziyan, additional, Choy, Desmond, additional, Caron, Jonathan, additional, Sosnowska, Dominika, additional, Beatson, Richard, additional, Muliaditan, Tamara, additional, An, Zhengwen, additional, Gillett, Cheryl E., additional, Lan, Guocheng, additional, Zou, Xiangang, additional, Watt, Fiona M., additional, Ng, Tony, additional, Burchell, Joy M., additional, Kordasti, Shahram, additional, Withers, David R., additional, Lawrence, Toby, additional, and Arnold, James N., additional

Published
2022
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15. LYVE-1 + Macrophages Form a Collaborative CCR5-Dependent Perivascular Niche That Influences Chemotherapy Responses in Cancer

Author

Anstee, Joanne E., primary, Opzoomer, James W., additional, Dean, Isaac, additional, Muller, Henrike P., additional, Bahri, Meriem, additional, Liakath-Ali, Kifayathullah, additional, Liu, Ziyan, additional, Choy, Desmond, additional, Caron, Jonathan, additional, Sosnowska, Dominika, additional, Beatson, Richard, additional, Muliaditan, Tamara, additional, An, Zhengwen, additional, Gillett, Cheryl E., additional, Lan, Guocheng, additional, Zou, Xiangang, additional, Watt, Fiona M., additional, Ng, Tony, additional, Burchell, Joy M., additional, Kordasti, Shahram, additional, Withers, David R., additional, Lawrence, Toby, additional, and Arnold, James N., additional

Published
2022
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16. A genome-wide screen identifies YAP/WBP2 interplay conferring growth advantage on human epidermal stem cells

Author

Walko, Gernot, Woodhouse, Samuel, Pisco, Angela Oliveira, Rognoni, Emanuel, Liakath-Ali, Kifayathullah, Lichtenberger, Beate M, Mishra, Ajay, Telerman, Stephanie B, Viswanathan, Priyalakshmi, Logtenberg, Meike, Renz, Lisa M, Donati, Giacomo, Quist, Sven R, Watt, Fiona M, Walko, Gernot [0000-0002-8504-1738], Rognoni, Emanuel [0000-0001-6050-2860], Liakath-Ali, Kifayathullah [0000-0001-9047-7424], Lichtenberger, Beate M [0000-0001-6882-0257], Mishra, Ajay [0000-0001-8201-4067], Viswanathan, Priyalakshmi [0000-0002-2169-6348], Logtenberg, Meike [0000-0002-8981-1189], Donati, Giacomo [0000-0002-0370-8288], Quist, Sven R [0000-0002-9548-7813], Watt, Fiona M [0000-0001-9151-5154], and Apollo - University of Cambridge Repository

Subjects
Mice, Knockout, integumentary system, Science, Stem Cells, Nuclear Proteins, Cell Cycle Proteins, Article, Mice, Inbred C57BL, Epidermal Cells, Gene Expression Regulation, Cell Line, Tumor, Mice, Inbred CBA, Trans-Activators, Animals, Humans, Female, Cells, Cultured, Adaptor Proteins, Signal Transducing, Cell Proliferation, Transcription Factors
Abstract

Individual human epidermal cells differ in their self-renewal ability. To uncover the molecular basis for this heterogeneity, we performed genome-wide pooled RNA interference screens and identified genes conferring a clonal growth advantage on normal and neoplastic (cutaneous squamous cell carcinoma, cSCC) human epidermal cells. The Hippo effector YAP was amongst the top positive growth regulators in both screens. By integrating the Hippo network interactome with our data sets, we identify WW-binding protein 2 (WBP2) as an important co-factor of YAP that enhances YAP/TEAD-mediated gene transcription. YAP and WPB2 are upregulated in actively proliferating cells of mouse and human epidermis and cSCC, and downregulated during terminal differentiation. WBP2 deletion in mouse skin results in reduced proliferation in neonatal and wounded adult epidermis. In reconstituted epidermis YAP/WBP2 activity is controlled by intercellular adhesion rather than canonical Hippo signalling. We propose that defective intercellular adhesion contributes to uncontrolled cSCC growth by preventing inhibition of YAP/WBP2., Individual human epidermal cells differ in their self-renewal ability. Here the authors perform genome-wide pooled RNAi screens to uncover the molecular basis for this heterogeneity, and identify genes conferring a clonal growth advantage on normal and neoplastic human epidermal cells.

Published
2019
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18. Immunomodulatory Role of Keratin 76 in Oral and Gastric Cancer

Author

Sequeira, Inês, primary, Neves, Joana F., additional, Carrero, Dido, additional, Peng, Qi, additional, Palasz, Natalia, additional, Liakath-Ali, Kifayathullah, additional, Lord, Graham M., additional, Morgan, Peter R., additional, Lombardi, Giovanna, additional, and Watt, Fiona M., additional

Published
2018
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19. Wounding induces dedifferentiation of epidermal Gata6 + cells and acquisition of stem cell properties

Author

Donati, Giacomo, Rognoni, Emanuel, Hiratsuka, Toru, Liakath-Ali, Kifayathullah, Hoste, Esther, Kar, Gozde, Kayikci, Melis, Russell, Roslin, Kretzschmar, Kai, Mulder, Klaas W., Teichmann, Sarah A., Watt, Fiona M., Donati, Giacomo, Rognoni, Emanuel, Hiratsuka, Toru, Liakath-Ali, Kifayathullah, Hoste, Esther, Kar, Gozde, Kayikci, Melis, Russell, Roslin, Kretzschmar, Kai, Mulder, Klaas W., Teichmann, Sarah A., and Watt, Fiona M.

Published
2017

20. Wounding induces dedifferentiation of epidermal Gata6 + cells and acquisition of stem cell properties

Author

Hubrecht Institute with UMC, Donati, Giacomo, Rognoni, Emanuel, Hiratsuka, Toru, Liakath-Ali, Kifayathullah, Hoste, Esther, Kar, Gozde, Kayikci, Melis, Russell, Roslin, Kretzschmar, Kai, Mulder, Klaas W., Teichmann, Sarah A., Watt, Fiona M., Hubrecht Institute with UMC, Donati, Giacomo, Rognoni, Emanuel, Hiratsuka, Toru, Liakath-Ali, Kifayathullah, Hoste, Esther, Kar, Gozde, Kayikci, Melis, Russell, Roslin, Kretzschmar, Kai, Mulder, Klaas W., Teichmann, Sarah A., and Watt, Fiona M.

Published
2017

21. Alkaline ceramidase 1 is essential for mammalian skin homeostasis and regulating whole body energy expenditure

Author

Liakath-Ali, Kifayathullah, Vancollie, Valerie E, Lelliott, Christopher J, Speak, Anneliese O, Lafont, David, Protheroe, Hayley J, Ingvorsen, Camilla, Galli, Antonella, Green, Angela, Gleeson, Diane, Ryder, Ed, Glover, Leanne, Vizcay-Barrena, Gema, Karp, Natasha A, Arends, Mark, Brenn, Thomas, Spiegel, Sarah, Adams, David J, Watt, Fiona M, and van der Weyden, Louise

Subjects
integumentary system
Abstract

The epidermis is the outermost layer of skin that acts as a barrier to protect the body from the external environment and to control water and heat loss. This barrier function is established through the multistage differentiation of keratinocytes and the presence of bioactive sphingolipids such as ceramides, the levels of which are tightly regulated by a balance of ceramide synthase and ceramidase activities. Here we reveal the essential role of alkaline ceramidase 1 (Acer1) in the skin. Acer1-deficient (Acer1(-/-) ) mice showed elevated levels of ceramide in the skin, aberrant hair shaft cuticle formation and cyclic alopecia. We demonstrate that Acer1 is specifically expressed in differentiated interfollicular epidermis, infundibulum and sebaceous glands and consequently Acer1(-/-) mice have significant alterations in infundibulum and sebaceous gland architecture. Acer1(-/-) skin also shows perturbed hair follicle stem cell compartments. These alterations result in Acer1(-/-) mice showing increased trans-epidermal water loss and a hyper-metabolism phenotype with associated reduction of fat content with age. We conclude that Acer1 is indispensable for mammalian skin homeostasis and whole body energy homeostasis.

Published
2016

22. A protein phosphatase network controls the temporal and spatial dynamics of differentiation commitment in human epidermis

Author

Mishra, Ajay, primary, Oulès, Bénédicte, additional, Pisco, Angela Oliveira, additional, Ly, Tony, additional, Liakath-Ali, Kifayathullah, additional, Walko, Gernot, additional, Viswanathan, Priyalakshmi, additional, Tihy, Matthieu, additional, Nijjher, Jagdeesh, additional, Dunn, Sara-Jane, additional, Lamond, Angus I, additional, and Watt, Fiona M, additional

Published
2017
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23. Author response: A protein phosphatase network controls the temporal and spatial dynamics of differentiation commitment in human epidermis

Author

Mishra, Ajay, primary, Oulès, Bénédicte, additional, Pisco, Angela Oliveira, additional, Ly, Tony, additional, Liakath-Ali, Kifayathullah, additional, Walko, Gernot, additional, Viswanathan, Priyalakshmi, additional, Tihy, Matthieu, additional, Nijjher, Jagdeesh, additional, Dunn, Sara-Jane, additional, Lamond, Angus I, additional, and Watt, Fiona M, additional

Published
2017
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24. Wounding induces dedifferentiation of epidermal Gata6+ cells and acquisition of stem cell properties

Author

Donati, Giacomo, primary, Rognoni, Emanuel, additional, Hiratsuka, Toru, additional, Liakath-Ali, Kifayathullah, additional, Hoste, Esther, additional, Kar, Gozde, additional, Kayikci, Melis, additional, Russell, Roslin, additional, Kretzschmar, Kai, additional, Mulder, Klaas W., additional, Teichmann, Sarah A., additional, and Watt, Fiona M., additional

Published
2017
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25. A genome-wide screen identifies YAP/WBP2 interplay conferring growth advantage on human epidermal stem cells

Author

Walko, Gernot, primary, Woodhouse, Samuel, additional, Pisco, Angela Oliveira, additional, Rognoni, Emanuel, additional, Liakath-Ali, Kifayathullah, additional, Lichtenberger, Beate M., additional, Mishra, Ajay, additional, Telerman, Stephanie B., additional, Viswanathan, Priyalakshmi, additional, Logtenberg, Meike, additional, Renz, Lisa M., additional, Donati, Giacomo, additional, Quist, Sven R., additional, and Watt, Fiona M., additional

Published
2017
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26. Myosin 10 is involved in murine pigmentation.

Author

Liakath‐Ali, Kifayathullah, Vancollie, Valerie E., Sequeira, Inês, Lelliott, Christopher J., and Watt, Fiona M.

Subjects
*ANIMAL coloration, *MOLECULAR motor proteins, *MYOSIN, *HAIR follicles, *MUSCLE physiology
Abstract

Myosins are molecular motors that are well known for their role in cell movement and contractile functions. Although extensively studied in muscle physiology, little is known about the function of myosins in mammalian skin. As part of the Sanger Institute Mouse Genetics Project, we have identified a role for Myo10 in pigmentation, with a phenotype unlike those of Myo5a or Myo7a. Adult mice homozygous for a disrupted Myo10 allele on a C57BL/6N background displayed a high degree of penetrance for white patches on their abdomen and dorsal surface. Forepaw syndactyly and hind paw syndactyly were also observed in these mice. Tail epidermal wholemounts showed a complete lack of melanocytes in the hair follicles and interfollicular epidermis. Myo10 has previously been implicated in human pigmentation. Our current study reveals involvement of Myo10 in murine skin pigmentation. [ABSTRACT FROM AUTHOR]

Published
2019
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27. Novel skin phenotypes revealed by a genome-wide mouse reverse genetic screen

Author

Liakath-Ali, Kifayathullah, Vancollie, Valerie E., Heath, Emma, Smedley, Damian P., Estabel, Jeanne, Sunter, David, DiTommaso, Tia, White, Jacqueline K., Ramirez-Solis, Ramiro, Smyth, Ian, Steel, Karen P., and Watt, Fiona M.

Subjects
Male, Mice, Knockout, Mice, Phenotype, integumentary system, Databases, Genetic, Mutation, Animals, Humans, Female, Article, Reverse Genetics, Skin
Abstract

Permanent stop-and-shop large-scale mouse mutant resources provide an excellent platform to decipher tissue phenogenomics. Here we analyse skin from 538 knockout mouse mutants generated by the Sanger Institute Mouse Genetics Project. We optimize immunolabelling of tail epidermal wholemounts to allow systematic annotation of hair follicle, sebaceous gland and interfollicular epidermal abnormalities using ontology terms from the Mammalian Phenotype Ontology. Of the 50 mutants with an epidermal phenotype, 9 map to human genetic conditions with skin abnormalities. Some mutant genes are expressed in the skin, whereas others are not, indicating systemic effects. One phenotype is affected by diet and several are incompletely penetrant. In-depth analysis of three mutants, Krt76, Myo5a (a model of human Griscelli syndrome) and Mysm1, provides validation of the screen. Our study is the first large-scale genome-wide tissue phenotype screen from the International Knockout Mouse Consortium and provides an open access resource for the scientific community., Large-scale efforts are put into the generation of knockout mutant mice for many individual genes. Here, the authors systematically screen skin from 538 mutant mice and identify 50 mutants with epidermal phenotypes, of which 9 are also associated with human skin defects.

Published
2014

28. Pelota Regulates Epidermal Differentiation by Modulating BMP and PI3K/AKT Signaling Pathways

Author

Elkenani, Manar, primary, Nyamsuren, Gunsmaa, additional, Raju, Priyadharsini, additional, Liakath-Ali, Kifayathullah, additional, Hamdaoui, Aicha, additional, Kata, Aleksandra, additional, Dressel, Ralf, additional, Klonisch, Thomas, additional, Watt, Fiona M., additional, Engel, Wolfgang, additional, Thliveris, James A., additional, Krishna Pantakani, D.V., additional, and Adham, Ibrahim M., additional

Published
2016
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29. Alkaline ceramidase 1 is essential for mammalian skin homeostasis and regulating whole-body energy expenditure

Author

Liakath-Ali, Kifayathullah, primary, Vancollie, Valerie E, additional, Lelliott, Christopher J, additional, Speak, Anneliese O, additional, Lafont, David, additional, Protheroe, Hayley J, additional, Ingvorsen, Camilla, additional, Galli, Antonella, additional, Green, Angela, additional, Gleeson, Diane, additional, Ryder, Ed, additional, Glover, Leanne, additional, Vizcay-Barrena, Gema, additional, Karp, Natasha A, additional, Arends, Mark J, additional, Brenn, Thomas, additional, Spiegel, Sarah, additional, Adams, David J, additional, Watt, Fiona M, additional, and van der Weyden, Louise, additional

Published
2016
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32. Over-expression of Plk4 induces centrosome amplification, loss of primary cilia and associated tissue hyperplasia in the mouse

Author

Coelho, Paula A., primary, Bury, Leah, additional, Shahbazi, Marta N., additional, Liakath-Ali, Kifayathullah, additional, Tate, Peri H., additional, Wormald, Sam, additional, Hindley, Christopher J., additional, Huch, Meritxell, additional, Archer, Joy, additional, Skarnes, William C., additional, Zernicka-Goetz, Magdalena, additional, and Glover, David M., additional

Published
2015
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33. Genome-wide Generation and Systematic Phenotyping of Knockout Mice Reveals New Roles for Many Genes

Author

White, Jacqueline K., primary, Gerdin, Anna-Karin, additional, Karp, Natasha A., additional, Ryder, Ed, additional, Buljan, Marija, additional, Bussell, James N., additional, Salisbury, Jennifer, additional, Clare, Simon, additional, Ingham, Neil J., additional, Podrini, Christine, additional, Houghton, Richard, additional, Estabel, Jeanne, additional, Bottomley, Joanna R., additional, Melvin, David G., additional, Sunter, David, additional, Adams, Niels C., additional, Tannahill, David, additional, Logan, Darren W., additional, MacArthur, Daniel G., additional, Flint, Jonathan, additional, Mahajan, Vinit B., additional, Tsang, Stephen H., additional, Smyth, Ian, additional, Watt, Fiona M., additional, Skarnes, William C., additional, Dougan, Gordon, additional, Adams, David J., additional, Ramirez-Solis, Ramiro, additional, Bradley, Allan, additional, Steel, Karen P., additional, Baker, Lauren, additional, Barnes, Caroline, additional, Beveridge, Ryan, additional, Cambridge, Emma, additional, Carragher, Damian, additional, Chana, Prabhjoat, additional, Clarke, Kay, additional, Hooks, Yvette, additional, Igosheva, Natalia, additional, Ismail, Ozama, additional, Jackson, Hannah, additional, Kane, Leanne, additional, Lacey, Rosalind, additional, Lafont, David Tino, additional, Lucas, Mark, additional, Maguire, Simon, additional, McGill, Katherine, additional, McIntyre, Rebecca E., additional, Messager, Sophie, additional, Mottram, Lynda, additional, Mulderrig, Lee, additional, Pearson, Selina, additional, Protheroe, Hayley J., additional, Roberson, Laura-Anne, additional, Salsbury, Grace, additional, Sanderson, Mark, additional, Sanger, Daniel, additional, Shannon, Carl, additional, Thompson, Paul C., additional, Tuck, Elizabeth, additional, Vancollie, Valerie E., additional, Brackenbury, Lisa, additional, Bushell, Wendy, additional, Cook, Ross, additional, Dalvi, Priya, additional, Gleeson, Diane, additional, Habib, Bishoy, additional, Hardy, Matt, additional, Liakath-Ali, Kifayathullah, additional, Miklejewska, Evelina, additional, Price, Stacey, additional, Sethi, Debarati, additional, Trenchard, Elizabeth, additional, von Schiller, Dominique, additional, Vyas, Sapna, additional, West, Anthony P., additional, Woodward, John, additional, Wynn, Elizabeth, additional, Evans, Arthur, additional, Gannon, David, additional, Griffiths, Mark, additional, Holroyd, Simon, additional, Iyer, Vivek, additional, Kipp, Christian, additional, Lewis, Morag, additional, Li, Wei, additional, Oakley, Darren, additional, Richardson, David, additional, Smedley, Damian, additional, Agu, Chukwuma, additional, Bryant, Jackie, additional, Delaney, Liz, additional, Gueorguieva, Nadia I., additional, Tharagonnet, Helen, additional, Townsend, Anne J., additional, Biggs, Daniel, additional, Brown, Ellen, additional, Collinson, Adam, additional, Dumeau, Charles-Etienne, additional, Grau, Evelyn, additional, Harrison, Sarah, additional, Harrison, James, additional, Ingle, Catherine E., additional, Kundi, Helen, additional, Madich, Alla, additional, Mayhew, Danielle, additional, Metcalf, Tom, additional, Newman, Stuart, additional, Pass, Johanna, additional, Pearson, Laila, additional, Reynolds, Helen, additional, Sinclair, Caroline, additional, Wardle-Jones, Hannah, additional, Woods, Michael, additional, Alexander, Liam, additional, Brown, Terry, additional, Flack, Francesca, additional, Frost, Carole, additional, Griggs, Nicola, additional, Hrnciarova, Silvia, additional, Kirton, Andrea, additional, McDermott, Jordan, additional, Rogerson, Claire, additional, White, Gemma, additional, Zielezinski, Pawel, additional, DiTommaso, Tia, additional, Edwards, Andrew, additional, Heath, Emma, additional, Mahajan, Mary Ann, additional, and Yalcin, Binnaz, additional

Published
2013
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34. Wounding induces dedifferentiation of epidermal Gata6+cells and acquisition of stem cell properties

Author

Donati, Giacomo, Rognoni, Emanuel, Hiratsuka, Toru, Liakath-Ali, Kifayathullah, Hoste, Esther, Kar, Gozde, Kayikci, Melis, Russell, Roslin, Kretzschmar, Kai, Mulder, Klaas W., Teichmann, Sarah A., and Watt, Fiona M.

Abstract

The epidermis is maintained by multiple stem cell populations whose progeny differentiate along diverse, and spatially distinct, lineages. Here we show that the transcription factor Gata6 controls the identity of the previously uncharacterized sebaceous duct (SD) lineage and identify the Gata6 downstream transcription factor network that specifies a lineage switch between sebocytes and SD cells. During wound healing differentiated Gata6+cells migrate from the SD into the interfollicular epidermis and dedifferentiate, acquiring the ability to undergo long-term self-renewal and differentiate into a much wider range of epidermal lineages than in undamaged tissue. Our data not only demonstrate that the structural and functional complexity of the junctional zone is regulated by Gata6, but also reveal that dedifferentiation is a previously unrecognized property of post-mitotic, terminally differentiated cells that have lost contact with the basement membrane. This resolves the long-standing debate about the contribution of terminally differentiated cells to epidermal wound repair.

Published
2017
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35. Alkaline ceramidase 1 is essential for mammalian skin homeostasis and regulating whole-body energy expenditure

Author

Liakath-Ali, Kifayathullah, Vancollie, Valerie E, Lelliott, Christopher J, Speak, Anneliese O, Lafont, David, Protheroe, Hayley J, Ingvorsen, Camilla, Galli, Antonella, Green, Angela, Gleeson, Diane, Ryder, Ed, Glover, Leanne, Vizcay-Barrena, Gema, Karp, Natasha A, Arends, Mark J, Brenn, Thomas, Spiegel, Sarah, Adams, David J, Watt, Fiona M, and Van Der Weyden, Louise

Subjects
Keratinocytes, Male, Sphingolipids, integumentary system, sebaceous glands, Alopecia, Cell Differentiation, Ceramides, 3. Good health, Mice, Inbred C57BL, Mice, skin homeostasis, Pituitary Gland, Skin Abnormalities, Alkaline Ceramidase, Animals, Homeostasis, Humans, Female, Epidermis, Energy Metabolism, energy homeostasis, Hair Follicle, ceramidase, Skin
Abstract

The epidermis is the outermost layer of skin that acts as a barrier to protect the body from the external environment and to control water and heat loss. This barrier function is established through the multistage differentiation of keratinocytes and the presence of bioactive sphingolipids such as ceramides, the levels of which are tightly regulated by a balance of ceramide synthase and ceramidase activities. Here we reveal the essential role of alkaline ceramidase 1 (Acer1) in the skin. Acer1-deficient (Acer1(-/-) ) mice showed elevated levels of ceramide in the skin, aberrant hair shaft cuticle formation and cyclic alopecia. We demonstrate that Acer1 is specifically expressed in differentiated interfollicular epidermis, infundibulum and sebaceous glands and consequently Acer1(-/-) mice have significant alterations in infundibulum and sebaceous gland architecture. Acer1(-/-) skin also shows perturbed hair follicle stem cell compartments. These alterations result in Acer1(-/-) mice showing increased transepidermal water loss and a hypermetabolism phenotype with associated reduction of fat content with age. We conclude that Acer1 is indispensable for mammalian skin homeostasis and whole-body energy homeostasis. © 2016 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.

36. Wounding induces dedifferentiation of epidermal Gata6 + cells and acquisition of stem cell properties.

Author

Donati G, Rognoni E, Hiratsuka T, Liakath-Ali K, Hoste E, Kar G, Kayikci M, Russell R, Kretzschmar K, Mulder KW, Teichmann SA, and Watt FM

Subjects
Animals, Cell Lineage, Cell Movement, Cell Plasticity, Cell Self Renewal, Cells, Cultured, Disease Models, Animal, Epidermis pathology, Female, GATA6 Transcription Factor deficiency, GATA6 Transcription Factor genetics, Male, Mice, Inbred C57BL, Mice, Knockout, Phenotype, Positive Regulatory Domain I-Binding Factor 1, Sebaceous Glands pathology, Signal Transduction, Time Factors, Transcription Factors genetics, Transcription Factors metabolism, Wounds and Injuries genetics, Wounds and Injuries pathology, Cell Dedifferentiation, Epidermis metabolism, GATA6 Transcription Factor metabolism, Sebaceous Glands metabolism, Stem Cells metabolism, Wound Healing, Wounds and Injuries metabolism
Abstract

The epidermis is maintained by multiple stem cell populations whose progeny differentiate along diverse, and spatially distinct, lineages. Here we show that the transcription factor Gata6 controls the identity of the previously uncharacterized sebaceous duct (SD) lineage and identify the Gata6 downstream transcription factor network that specifies a lineage switch between sebocytes and SD cells. During wound healing differentiated Gata6 + cells migrate from the SD into the interfollicular epidermis and dedifferentiate, acquiring the ability to undergo long-term self-renewal and differentiate into a much wider range of epidermal lineages than in undamaged tissue. Our data not only demonstrate that the structural and functional complexity of the junctional zone is regulated by Gata6, but also reveal that dedifferentiation is a previously unrecognized property of post-mitotic, terminally differentiated cells that have lost contact with the basement membrane. This resolves the long-standing debate about the contribution of terminally differentiated cells to epidermal wound repair.

Published
2017
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