Optogenetic control of YAP reveals a dynamic communication code for stem cell fate and proliferation

Kirstin Meyer; Nicholas C Lammers; Lukasz J Bugaj; Hernan G Garcia; Orion D Weiner

doi:10.1038/s41467-023-42643-2

Optogenetic control of YAP reveals a dynamic communication code for stem cell fate and proliferation

Nat Commun. 2023 Oct 30;14(1):6929. doi: 10.1038/s41467-023-42643-2.

Authors

Kirstin Meyer^{1

2}, Nicholas C Lammers^{3

4}, Lukasz J Bugaj⁵, Hernan G Garcia^{3

6

7

8

9}, Orion D Weiner^{10

11}

Affiliations

¹ Cardiovascular Research Institute, University of California, San Francisco, San Francisco, CA, USA.
² Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA, USA.
³ Biophysics Graduate Group, University of California at Berkeley, Berkeley, CA, USA.
⁴ Department of Genome Sciences, University of Washington, Seattle, WA, USA.
⁵ Department of Bioengineering, University of Pennsylvania, Philadelphia, PA, USA.
⁶ Department of Physics, University of California at Berkeley, Berkeley, CA, USA.
⁷ Department of Molecular and Cell Biology, University of California Berkeley, Berkeley, CA, USA.
⁸ Institute for Quantitative Biosciences-QB3, University of California at Berkeley, Berkeley, CA, USA.
⁹ Chan Zuckerberg Biohub, San Francisco, CA, USA.
¹⁰ Cardiovascular Research Institute, University of California, San Francisco, San Francisco, CA, USA. orion.weiner@ucsf.edu.
¹¹ Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA, USA. orion.weiner@ucsf.edu.

Abstract

YAP is a transcriptional regulator that controls pluripotency, cell fate, and proliferation. How cells ensure the selective activation of YAP effector genes is unknown. This knowledge is essential to rationally control cellular decision-making. Here we leverage optogenetics, live-imaging of transcription, and cell fate analysis to understand and control gene activation and cell behavior. We reveal that cells decode the steady-state concentrations and timing of YAP activation to control proliferation, cell fate, and expression of the pluripotency regulators Oct4 and Nanog. While oscillatory YAP inputs induce Oct4 expression and proliferation optimally at frequencies that mimic native dynamics, cellular differentiation requires persistently low YAP levels. We identify the molecular logic of the Oct4 dynamic decoder, which acts through an adaptive change sensor. Our work reveals how YAP levels and dynamics enable multiplexing of information transmission for the regulation of developmental decision-making and establishes a platform for the rational control of these behaviors.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Cell Communication
Cell Differentiation / genetics
Cell Proliferation / genetics
Optogenetics*
Stem Cells*

Abstract

Publication types

MeSH terms

Grants and funding