PT  - JOURNAL ARTICLE
AU  - Linghu, Changyang
AU  - An, Bobae
AU  - Shpokayte, Monika
AU  - Celiker, Orhan T.
AU  - Shmoel, Nava
AU  - Zhang, Chi
AU  - Park, Won Min
AU  - Ramirez, Steve
AU  - Boyden, Edward S.
TI  - Recording of cellular physiological histories along optically readable self-assembling protein chains
AID  - 10.1101/2021.10.13.464006
DP  - 2021 Jan 01
TA  - bioRxiv
PG  - 2021.10.13.464006
4099  - http://biorxiv.org/content/early/2021/10/13/2021.10.13.464006.short
4100  - http://biorxiv.org/content/early/2021/10/13/2021.10.13.464006.full
AB  - Observing cellular physiological histories is key to understanding normal and disease-related processes, but longitudinal imaging is laborious and equipment-intensive. A tantalizing possibility is that cells could record such histories in the form of digital biological information within themselves, for later high-throughput readout. Here we show that this concept can be realized through information storage in the form of growing protein chains made out of multiple self-assembling subunits bearing different labels, each corresponding to a different cellular state or function, so that the physiological history of the cell can be visually read out along the chain of proteins. Conveniently, such protein chains are fully genetically encoded, and easily readable with simple, conventional optical microscopy techniques, compatible with visualization of cellular shape and molecular content. We use such expression recording islands (XRIs) to record gene expression timecourse downstream of pharmacological and physiological stimuli, in cultured neurons and in living mouse brain.Competing Interest StatementC.L. and E.S.B. declare they applied for a US patent based on the work presented in this paper.