S-BIAD992alpha

A live-cell screen for altered Erk dynamics reveals principles of proliferative control (OME-NGFF)

Released 2024-01-04
Image Data Resource (IDR)

Content

  • 9 images
  • Study size: 43.7GiB
  • N files: 9
  • Filetype breakdown:
    • .ome.zarr.zip: 9 (43.7GiB)
OME-NGFF converted study from idr0064. Complex, time-varying responses have been observed widely in cell signaling, but how specific dynamics are generated or regulated is largely unknown. One major obstacle has been that high-throughput screens for identifying pathway components are typically incompatible with the live-cell assays used to monitor dynamics. Here, we address this challenge by performing a drug screen for altered Erk signaling dynamics in primary mouse keratinocytes. We screened a library of 429 kinase inhibitors, monitoring Erk activity over 5 h in more than 80,000 single live cells. The screen revealed both known and uncharacterized modulators of Erk dynamics, including inhibitors of non-EGFR receptor tyrosine kinases (RTKs) that increased Erk pulse frequency and overall activity. Using drug treatment and direct optogenetic control, we demonstrate that drug-induced changes to Erk dynamics alter the conditions under which cells proliferate. Our work opens the door to high-throughput screens using live-cell biosensors and reveals that cell proliferation integrates information from Erk dynamics as well as additional permissive cues.

Study information

Organism
Mus musculus (mouse)
Imaging type
spinning disk confocal microscopy
License
CC BY 4.0

Viewable images

Image ID Preview Filename Dimensions
(T, C, Z, Y, X)		 Download Size Actions
IM1 idr0064/3.3.ome.zarr.zip None 4.7GiB
IM2 idr0064/3.1.ome.zarr.zip None 4.9GiB
IM3 idr0064/1.3.ome.zarr.zip None 4.9GiB
IM4 idr0064/1.2.ome.zarr.zip None 5.0GiB
IM5 idr0064/2.2.ome.zarr.zip None 4.8GiB
IM6 idr0064/2.1.ome.zarr.zip None 4.8GiB
IM7 idr0064/3.2.ome.zarr.zip None 4.7GiB
IM8 idr0064/2.3.ome.zarr.zip None 5.1GiB
IM9 idr0064/1.1.ome.zarr.zip None 4.7GiB

All images

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Image ID Filename Download Size Actions
IM1 idr0064/3.3.ome.zarr.zip 4.7GiB Download
IM2 idr0064/3.1.ome.zarr.zip 4.9GiB Download
IM3 idr0064/1.3.ome.zarr.zip 4.9GiB Download
IM4 idr0064/1.2.ome.zarr.zip 5.0GiB Download
IM5 idr0064/2.2.ome.zarr.zip 4.8GiB Download
IM6 idr0064/2.1.ome.zarr.zip 4.8GiB Download
IM7 idr0064/3.2.ome.zarr.zip 4.7GiB Download
IM8 idr0064/2.3.ome.zarr.zip 5.1GiB Download
IM9 idr0064/1.1.ome.zarr.zip 4.7GiB Download