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Imaging cell lineage with a synthetic digital recording system

Chow, Ke-Huan K. and Budde, Mark W. and Granados, Alejandro A. and Cabrera, Maria and Yoon, Shinae and Cho, Soomin and Huang, Ting-hao and Koulena, Noushin and Frieda, Kirsten L. and Cai, Long and Lois, Carlos and Elowitz, Michael B. (2020) Imaging cell lineage with a synthetic digital recording system. . (Unpublished)

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Multicellular development depends on the differentiation of cells into specific fates with precise spatial organization. Lineage history plays a pivotal role in cell fate decisions, but is inaccessible in most contexts. Engineering cells to actively record lineage information in a format readable in situ would provide a spatially resolved view of lineage in diverse developmental processes. Here, we introduce a serine integrase-based recording system that allows in situ readout, and demonstrate its ability to reconstruct lineage relationships in cultured stem cells and flies. The system, termed intMEMOIR, employs an array of independent three-state genetic memory elements that can recombine stochastically and irreversibly, allowing up to 59,049 distinct digital states. intMEMOIR accurately reconstructed lineage trees in stem cells and enabled simultaneous analysis of single cell clonal history, spatial position, and gene expression in Drosophila brain sections. These results establish a foundation for microscopy-readable clonal analysis and recording in diverse systems.

Item Type:Report or Paper (Discussion Paper)
Related URLs:
URLURL TypeDescription Paper
Huang, Ting-hao0000-0002-2546-3525
Koulena, Noushin0000-0002-9419-5712
Cai, Long0000-0002-7154-5361
Lois, Carlos0000-0002-7305-2317
Elowitz, Michael B.0000-0002-1221-0967
Additional Information:The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. We thank L. Sanchez-Guardado, H. Choi, C. Calvert, G. Shin, C. Tischbirek, S. Shah, and N. Pierson for technical assistnace and advice. A. Askary, X. Gao, F. Horns, D. Chadley, C. Su, and other members of the Elowitz lab for critical feedback on the manuscript . A. Shur, P. Meyer, R. Lu, and J. Linton for scientific input and advice. This research was funded by the National Institutes of Health (NIH) (grant R01 MH116508 to M.B.E., C.L., and L.C.), the Paul G. Allen Frontiers Group and Prime Awarding Agency (grant UWSC10142 to M.B.E., C.L., and L.C.), K.L.F. holds a Career Award at the Scientific Interface from BWF, and M.B.E. is a Howard Hughes Medical Institute investigator. K.K.C., M.W.B., A.A.G., K.L.F., L.C., C.L., and M.B.E. designed research. K.K.C., M.W.B., M.C., S.Y., S.C., and N.K. performed experiments. A.A.G., M.W.B., K.K.C., T.H., C.L., and M.B.E analyzed data, K.K.C., M.W.B., A.A.G., C.L., and M.B.E. wrote the manuscript. Competing interests: K.L.F., K.K.C., L.C., and M.B.E., are inventors on a patent application for recording technologies.
Funding AgencyGrant Number
NIHR01 MH116508
Paul G. Allen Frontiers GroupUWSC10142
Burroughs Wellcome FundUNSPECIFIED
Howard Hughes Medical Institute (HHMI)UNSPECIFIED
Record Number:CaltechAUTHORS:20200225-135944187
Persistent URL:
Official Citation:Imaging cell lineage with a synthetic digital recording system Ke-Huan K Chow, Mark W Budde, Alejandro A Granados, Maria Cabrera, Shinae Yoon, Soomin Cho, Ting-hao Huang, Noushin Koulena, Kirsten L Frieda, Long Cai, Carlos Lois, Michael B Elowitz bioRxiv 2020.02.21.958678; doi:
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:101552
Deposited By: George Porter
Deposited On:26 Feb 2020 15:49
Last Modified:07 Jul 2020 20:15

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