From recording to intervention: causal lineage tracing with primed conversion
File(s)
Author(s)
Boecker, Julian Raphael
Pantazis, Periklis
Type
Journal Article
Abstract
Abstract—Predicting cell fate requires reconstructing a cell’s integrated history: its lineage, the signals it received, how its internal state evolved and its spatial context. Existing recording methods write this information into DNA and read it only at the experiment’s end, allowing reconstruction of what happened but not testing whether it was required. Closing this gap demands real-time observation with the capacity to intervene: perturbing
specific cells based on what is observed, while sparing others as matched controls. Primed conversion, a dual-wavelength photoconversion method, confines activation to a single cell in three dimensions by requiring both blue and red light beams to intersect. The same photochemistry can release optogenetic actuators, so a single illumination both marks and edits a cell. Combined with oblique plane microscopy for continuous volumetric imaging, this architecture enables conditional intervention throughout development or tumour evolution, generating genetic
mosaics with internal controls that turn lineage tracing from
passive recording into an experimental test of which events were required for a given fate. In this perspective, an integrated optical platform is outlined that couples primed conversion, optogenetic actuators and oblique plane microscopy to achieve causal, real time intervention on defined cells.
specific cells based on what is observed, while sparing others as matched controls. Primed conversion, a dual-wavelength photoconversion method, confines activation to a single cell in three dimensions by requiring both blue and red light beams to intersect. The same photochemistry can release optogenetic actuators, so a single illumination both marks and edits a cell. Combined with oblique plane microscopy for continuous volumetric imaging, this architecture enables conditional intervention throughout development or tumour evolution, generating genetic
mosaics with internal controls that turn lineage tracing from
passive recording into an experimental test of which events were required for a given fate. In this perspective, an integrated optical platform is outlined that couples primed conversion, optogenetic actuators and oblique plane microscopy to achieve causal, real time intervention on defined cells.
Date Acceptance
2026-01-28
Citation
IEEE Photonics Journal
ISSN
1943-0655
Publisher
IEEE
Journal / Book Title
IEEE Photonics Journal
Copyright Statement
Copyright © 2026 Copyright Owner. This is the author’s accepted manuscript made available under a CC-BY licence in accordance with Imperial’s Research Publications Open Access policy (www.imperial.ac.uk/oa-policy)
License URL
Publication Status
Accepted