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Your search keyword '"Liakath-Ali, Kifayathullah"' showing total 3 results
Start Over Author "Liakath-Ali, Kifayathullah" Topic cell differentiation
3 results on '"Liakath-Ali, Kifayathullah"'

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

Author

Mishra A, Oulès B, Pisco AO, Ly T, Liakath-Ali K, Walko G, Viswanathan P, Tihy M, Nijjher J, Dunn SJ, Lamond AI, and Watt FM

Subjects
Cells, Cultured, Gene Expression Profiling, Humans, Proteome analysis, Cell Differentiation, Gene Expression Regulation, Keratinocytes enzymology, Keratinocytes physiology, Phosphoprotein Phosphatases metabolism
Abstract

Epidermal homeostasis depends on a balance between stem cell renewal and terminal differentiation. The transition between the two cell states, termed commitment, is poorly understood. Here, we characterise commitment by integrating transcriptomic and proteomic data from disaggregated primary human keratinocytes held in suspension to induce differentiation. Cell detachment induces several protein phosphatases, five of which - DUSP6, PPTC7, PTPN1, PTPN13 and PPP3CA - promote differentiation by negatively regulating ERK MAPK and positively regulating AP1 transcription factors. Conversely, DUSP10 expression antagonises commitment. The phosphatases form a dynamic network of transient positive and negative interactions that change over time, with DUSP6 predominating at commitment. Boolean network modelling identifies a mandatory switch between two stable states (stem and differentiated) via an unstable (committed) state. Phosphatase expression is also spatially regulated in vivo and in vitro. We conclude that an auto-regulatory phosphatase network maintains epidermal homeostasis by controlling the onset and duration of commitment.

Published
2017
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2. 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, van der Weyden, Louise, Vancollie, Valerie E [0000-0003-1547-1975], and Apollo - University of Cambridge Repository

Subjects
Keratinocytes, Male, Sphingolipids, integumentary system, sebaceous glands, Alopecia, Cell Differentiation, Ceramides, 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.

Published
2016

3. 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.

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