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Published April 9, 2021 | Supplemental Material + Submitted
Journal Article Open

Imaging cell lineage with a synthetic digital recording system


Cell lineage plays a pivotal role in cell fate determination. Chow et al. demonstrate the use of an integrase-based synthetic barcode system called intMEMOIR, which uses the serine integrase Bxb1 to perform irreversible nucleotide edits. Inducible editing either deletes or inverts its target region, thus encoding information in three-state memory elements, or trits, and avoiding undesired recombination events. Using intMEMOIR combined with single-molecule fluorescence in situ hybridization, the authors were able to identify clonal structures as well as gene expression patterns in the fly brain, enabling both clonal analysis and expression profiling with intact spatial information. The ability to visualize cell lineage relationships directly within their native tissue context provides insights into development and disease.

Additional Information

© 2021 American Association for the Advancement of Science. This is an article distributed under the terms of the Science Journals Default License. Received 20 February 2020; accepted 25 February 2021. We thank L. Sanchez-Guardado, H. Choi, C. Calvert, G. Shin, C. Tischbirek, Y. Takei, S. Shah, and N. Pierson for technical assistance and advice; A. Askary, X. Gao, F. Horns, D. Chadly, C. Su, and other members of the Elowitz lab for critical feedback on the manuscript; and A. Shur, P. Meyer, R. Lu, and J. Linton for scientific input and advice. Funding: This research was supported by the Allen Discovery Center program, a Paul G. Allen Frontiers Group advised program of the Paul G. Allen Family Foundation (grant UWSC10142 to M.B.E., C.L., and L.C.), the National Institutes of Health (NIH) (grant R01 MH116508 to M.B.E., C.L., and L.C.), and Burroughs Wellcome Fund CASI (K.L.F.), and M.B.E. is a Howard Hughes Medical Institute investigator. M.B.E. acknowledges Fritz Thyssen Stiftung for support for a visiting fellowship to Berlin. Authors contributions: 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. Data and materials availability: Plasmids to implement intMEMOIR in mES cells and Drosophila melanogaster are available from the Addgene repository (ID: 158387, 158389, 158390, and 158391), Drosophila melanogaster lines are available from the Bloomington repository (RRID: BDSC_90853 and BDSC_90854), and the intMEM1 cell line will be made available from C.L. and M.B.E. under the terms of the Uniform Biological Material Transfer Agreement (UBMTA). The data, code, and analysis to generate the results in the manuscript and the sequence information of relevant constructs are freely available on (63).

Attached Files

Submitted - 2020.02.21.958678v2.full.pdf

Supplemental Material - abb3099_Chow_SM.pdf

Supplemental Material - abb3099_Reproducibility_Checklist.pdf

Supplemental Material - abb3099_table_S1.xlsx

Supplemental Material - abb3099_table_S2.xlsx

Supplemental Material - abb3099_table_S3.xlsx

Supplemental Material - abb3099_table_S4.xlsx

Supplemental Material - abb3099s1.mp4

Supplemental Material - abb3099s2.mp4

Supplemental Material - abb3099s3.mp4


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Additional details

August 20, 2023
December 22, 2023