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

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

doi:10.1038/ncomms14744

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

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

Centre for Stem Cells & Regenerative Medicine

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

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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.

Original language	English
Pages (from-to)	14744
Journal	Nature Communications
Volume	8
Early online date	23 Mar 2017
DOIs	https://doi.org/10.1038/ncomms14744
Publication status	Published - 23 Mar 2017

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Walko, G., Woodhouse, S., Pisco, A. O., Rognoni, E., Liakath-Ali, K., Lichtenberger, B. M., Mishra, A., Telerman, S. B., Viswanathan, P., Logtenberg, M., Renz, L. M., Donati, G., Quist, S. R., & Watt, F. M. (2017). A genome-wide screen identifies YAP/WBP2 interplay conferring growth advantage on human epidermal stem cells. Nature Communications, 8, 14744. https://doi.org/10.1038/ncomms14744

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title = "A genome-wide screen identifies YAP/WBP2 interplay conferring growth advantage on human epidermal stem cells",

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.",

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

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Walko, G , Woodhouse, S , Pisco, AO , Rognoni, E, Liakath-Ali, K, Lichtenberger, BM , Mishra, A , Telerman, SB , Viswanathan, P, Logtenberg, M, Renz, LM, Donati, G, Quist, SR & Watt, FM 2017, 'A genome-wide screen identifies YAP/WBP2 interplay conferring growth advantage on human epidermal stem cells', Nature Communications, vol. 8, pp. 14744. https://doi.org/10.1038/ncomms14744

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T1 - A genome-wide screen identifies YAP/WBP2 interplay conferring growth advantage on human epidermal stem cells

AU - Walko, Gernot

AU - Woodhouse, Samuel

AU - Pisco, Angela Oliveira

AU - Rognoni, Emanuel

AU - Liakath-Ali, Kifayathullah

AU - Lichtenberger, Beate M

AU - Mishra, Ajay

AU - Telerman, Stephanie B

AU - Viswanathan, Priyalakshmi

AU - Logtenberg, Meike

AU - Renz, Lisa M

AU - Donati, Giacomo

AU - Quist, Sven R

AU - Watt, Fiona M

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Y1 - 2017/3/23

N2 - 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.

AB - 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.

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DO - 10.1038/ncomms14744

M3 - Article

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SN - 2041-1723

VL - 8

SP - 14744

JO - Nature Communications

JF - Nature Communications

ER -

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

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