TY - JOUR
T1 - YAP regulates cell size and growth dynamics via non-cell autonomous mediators
AU - Mugahid, Douaa
AU - Kalocsay, Marian
AU - Liu, Xili
AU - Gruver, Jonathan Scott
AU - Peshkin, Leonid
AU - Kirschner, Marc W.
N1 - Funding Information:
We thank Mike Gage for his meticulous assistance with the preparation of the protein samples for mass spectrometry and his overall management of project resources. We thank Jodene Moore of the SysBio FACS facility for her indispensable help setting up FACS analyses on the facility machines. We also thank the BPF Next-Gen Sequencing Core Facility at Harvard Medical School for their expertise and instrument availability that supported this work. We are grateful to the Nikon Imaging.
Funding Information:
We thank Mike Gage for his meticulous assistance with the preparation of the protein samples for mass spectrometry and his overall management of project resources. We thank Jodene Moore of the SysBio FACS facility for her indispensable help setting up FACS analyses on the facility machines. We also thank the BPF Next-Gen Sequencing Core Facility at Harvard Medical School for their expertise and instrument availability that supported this work. We are grateful to the Nikon Imaging Center at Harvard Medical School for sharing resources; and to the Research Computing Group for support with cluster computing for image processing, RNAseq data processing and data transfer. We are grateful for funding from HMS through the Dean’s Innovation grant. Finally, we are grateful to Shangqin Guo and Amaleah Hartman for the stimulating discussions and thoughtful critique of this paper.
Publisher Copyright:
© Mugahid et al.
PY - 2020/1
Y1 - 2020/1
N2 - The Hippo pathway regulates organ size, regeneration, and cell growth by controlling the stability of the transcription factor, YAP (Yorkie in Drosophila). When there is tissue damage, YAP is activated allowing the restoration of homeostatic tissue size. The exact signals by which YAP is activated are still not fully understood, but its activation is known to affect both cell size and cell number. Here we used cultured cells to examine the coordinated regulation of cell size and number under the control of YAP. Our experiments in isogenic HEK293 cells reveal that YAP can affect cell size and number by independent circuits. Some of these effects are cell autonomous, such as proliferation, while others are mediated by secreted signals. In particular CYR61, a known secreted YAP target, is a non-cell autonomous mediator of cell survival, while another unidentified secreted factor controls cell size.
AB - The Hippo pathway regulates organ size, regeneration, and cell growth by controlling the stability of the transcription factor, YAP (Yorkie in Drosophila). When there is tissue damage, YAP is activated allowing the restoration of homeostatic tissue size. The exact signals by which YAP is activated are still not fully understood, but its activation is known to affect both cell size and cell number. Here we used cultured cells to examine the coordinated regulation of cell size and number under the control of YAP. Our experiments in isogenic HEK293 cells reveal that YAP can affect cell size and number by independent circuits. Some of these effects are cell autonomous, such as proliferation, while others are mediated by secreted signals. In particular CYR61, a known secreted YAP target, is a non-cell autonomous mediator of cell survival, while another unidentified secreted factor controls cell size.
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U2 - 10.7554/eLife.53404
DO - 10.7554/eLife.53404
M3 - Article
C2 - 31913124
AN - SCOPUS:85078684388
SN - 2050-084X
VL - 9
JO - eLife
JF - eLife
M1 - e53404
ER -