Genetic recording and in situ readout of single-cell signaling memory.

Kai Hao, Yunzheng Liu, Mykel Barrett, Zainalabedin Samadi, Amirhossein Zarezadeh, Yuka McGrath, Magdalena Zernicka-Goetz, Amjad Askary

Abstract read

PubMed Publisher

In one paragraph

Article in Nature chemical biology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it

0cells of the map it votes in

0citing papers in PubMed

–field-weighted citation impact

1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors.

Kai HaoDepartment of Molecular, Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, CA, USA.ORCID http://orcid.org/0000-0002-8458-3404

Yunzheng LiuBiology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA.ORCID http://orcid.org/0009-0003-0559-7440

Mykel BarrettDepartment of Molecular, Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, CA, USA.ORCID http://orcid.org/0000-0003-4620-4116

Zainalabedin SamadiDepartment of Molecular, Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, CA, USA.

Amirhossein ZarezadehDepartment of Molecular, Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, CA, USA.ORCID http://orcid.org/0009-0002-1010-691X

Yuka McGrathDepartment of Molecular, Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, CA, USA.

Magdalena Zernicka-GoetzBiology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA.

Amjad AskaryDepartment of Molecular, Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, CA, USA. amjada@ucla.edu.ORCID http://orcid.org/0000-0002-2913-8498

Funding

Synthetic recording and in situ readout of cell lineage and molecular history in mammalian retinaR00EY031782 · NEI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI ASKARY, AMJAD · 2022 to 2024

$747k

U.S. Department of Health & Human Services | NIH | National Eye Institute (NEI) R00EY031782

6 · The paper itself

Abstract

Intensity and duration of biological signals encode a few pathways to direct diverse cellular behaviors, yet quantifying these features in single cells remains difficult. To address this challenge, we developed INSCRIBE, which uses a CRISPR base editor to mutate genomic targets at rates proportional to signaling activity. Edits are recovered at the endpoint through a new ratiometric readout strategy from images of two fluorescence channels. We engineered human cells to record WNT and BMP activity. Following defined exogenous stimulations, INSCRIBE accurately recovered signal intensity in dose-response experiments and exposure duration in time-course experiments. Applying INSCRIBE revealed a persistent memory in the BMP pathway, where progeny of high-responding cells remained more sensitive to subsequent BMP stimulation for up to 3 weeks. Together, our results establish a scalable platform for genetic recording and in situ readout of signaling activity in single cells, advancing quantitative analysis of cell-cell communication during development and disease.

Identifiers

PMID41813882

DOI10.1038/s41592-019-0582-9

What Socratic holds

Textmetadata

Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.