Differential transcription factor expression by human epithelial cells of buccal and urothelial derivation

Jennifer Southgate; Arianna Hustler; Ian Eardley; Jennifer Susan Hinley; Joanna Frances Pearson; Felix Wezel; François Radvanyi; Simon Charles Baker

doi:10.1016/j.yexcr.2018.05.031

Differential transcription factor expression by human epithelial cells of buccal and urothelial derivation

Jennifer Southgate, Arianna Hustler, Ian Eardley, Jennifer Susan Hinley, Joanna Frances Pearson, Felix Wezel, François Radvanyi, Simon Charles Baker

Research output: Contribution to journal › Article › peer-review

Abstract

Identification of transcription factors expressed by differentiated cells is informative not only of tissue-specific pathways, but to help identify master regulators for cellular reprogramming. If applied, such an approach could generate healthy autologous tissue-specific cells for clinical use where cells from the homologous tissue are unavailable due to disease. Normal human epithelial cells of buccal and urothelial derivation maintained in identical culture conditions that lacked significant instructive or permissive signalling cues were found to display inherent similarities and differences of phenotype. Investigation of transcription factors implicated in driving urothelial-type differentiation revealed buccal epithelial cells to have minimal or absent expression of PPARG, GATA3 and FOXA1 genes. Retroviral overexpression of GATA3 or PPARG1 coding sequences in buccal epithelial cells resulted in nuclear immunolocalisation of the respective proteins, with both transductions also inducing expression of the urothelial differentiation-associated claudin 3 tight junction protein. PPARγ1 overexpression alone entrained expression of nuclear FOXA1 and GATA3 proteins, providing objective evidence of its upstream positioning in a transcription factor network and identifying it as a candidate factor for urothelial-type transdifferentiation or reprogramming.

Original language	English
Pages (from-to)	284-294
Number of pages	11
Journal	Experimental cell research
Volume	369
Issue number	2
Early online date	26 May 2018
DOIs	https://doi.org/10.1016/j.yexcr.2018.05.031
Publication status	Published - 15 Aug 2018

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10.1016/j.yexcr.2018.05.031

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© 2018 The Authors.
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Cite this

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title = "Differential transcription factor expression by human epithelial cells of buccal and urothelial derivation",

abstract = "Identification of transcription factors expressed by differentiated cells is informative not only of tissue-specific pathways, but to help identify master regulators for cellular reprogramming. If applied, such an approach could generate healthy autologous tissue-specific cells for clinical use where cells from the homologous tissue are unavailable due to disease. Normal human epithelial cells of buccal and urothelial derivation maintained in identical culture conditions that lacked significant instructive or permissive signalling cues were found to display inherent similarities and differences of phenotype. Investigation of transcription factors implicated in driving urothelial-type differentiation revealed buccal epithelial cells to have minimal or absent expression of PPARG, GATA3 and FOXA1 genes. Retroviral overexpression of GATA3 or PPARG1 coding sequences in buccal epithelial cells resulted in nuclear immunolocalisation of the respective proteins, with both transductions also inducing expression of the urothelial differentiation-associated claudin 3 tight junction protein. PPARγ1 overexpression alone entrained expression of nuclear FOXA1 and GATA3 proteins, providing objective evidence of its upstream positioning in a transcription factor network and identifying it as a candidate factor for urothelial-type transdifferentiation or reprogramming.",

author = "Jennifer Southgate and Arianna Hustler and Ian Eardley and Hinley, {Jennifer Susan} and Pearson, {Joanna Frances} and Felix Wezel and Fran{\c c}ois Radvanyi and Baker, {Simon Charles}",

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doi = "10.1016/j.yexcr.2018.05.031",

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T1 - Differential transcription factor expression by human epithelial cells of buccal and urothelial derivation

AU - Southgate, Jennifer

AU - Hustler, Arianna

AU - Eardley, Ian

AU - Hinley, Jennifer Susan

AU - Pearson, Joanna Frances

AU - Wezel, Felix

AU - Radvanyi, François

AU - Baker, Simon Charles

PY - 2018/8/15

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N2 - Identification of transcription factors expressed by differentiated cells is informative not only of tissue-specific pathways, but to help identify master regulators for cellular reprogramming. If applied, such an approach could generate healthy autologous tissue-specific cells for clinical use where cells from the homologous tissue are unavailable due to disease. Normal human epithelial cells of buccal and urothelial derivation maintained in identical culture conditions that lacked significant instructive or permissive signalling cues were found to display inherent similarities and differences of phenotype. Investigation of transcription factors implicated in driving urothelial-type differentiation revealed buccal epithelial cells to have minimal or absent expression of PPARG, GATA3 and FOXA1 genes. Retroviral overexpression of GATA3 or PPARG1 coding sequences in buccal epithelial cells resulted in nuclear immunolocalisation of the respective proteins, with both transductions also inducing expression of the urothelial differentiation-associated claudin 3 tight junction protein. PPARγ1 overexpression alone entrained expression of nuclear FOXA1 and GATA3 proteins, providing objective evidence of its upstream positioning in a transcription factor network and identifying it as a candidate factor for urothelial-type transdifferentiation or reprogramming.

AB - Identification of transcription factors expressed by differentiated cells is informative not only of tissue-specific pathways, but to help identify master regulators for cellular reprogramming. If applied, such an approach could generate healthy autologous tissue-specific cells for clinical use where cells from the homologous tissue are unavailable due to disease. Normal human epithelial cells of buccal and urothelial derivation maintained in identical culture conditions that lacked significant instructive or permissive signalling cues were found to display inherent similarities and differences of phenotype. Investigation of transcription factors implicated in driving urothelial-type differentiation revealed buccal epithelial cells to have minimal or absent expression of PPARG, GATA3 and FOXA1 genes. Retroviral overexpression of GATA3 or PPARG1 coding sequences in buccal epithelial cells resulted in nuclear immunolocalisation of the respective proteins, with both transductions also inducing expression of the urothelial differentiation-associated claudin 3 tight junction protein. PPARγ1 overexpression alone entrained expression of nuclear FOXA1 and GATA3 proteins, providing objective evidence of its upstream positioning in a transcription factor network and identifying it as a candidate factor for urothelial-type transdifferentiation or reprogramming.

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