High-resolution spatial mapping of cell state and lineage dynamics in vivo with PEtracer

Luke W Koblan^#^{1

2

3}, Kathryn E Yost^#^{1

2

3}, Pu Zheng^#^{1

2

3}, William N Colgan^#^{1

2

3}, Matthew G Jones⁴, Dian Yang^{5

6}, Arhan Kumar^{1

2

3}, Jaspreet Sandhu^{1

2

3

7}, Alexandra Schnell^{1

2

3}, Dawei Sun^{8

9}, Can Ergen^{10

11}, Reuben A Saunders^{1

2

3

12}, Xiaowei Zhuang^{2

13

14}, William E Allen^{2

12}, Nir Yosef¹⁵, Jonathan S Weissman^{1

2

3

16}

Affiliations

¹ Whitehead Institute for Biomedical Research, Cambridge, MA, USA.
² Howard Hughes Medical Institute, Chevy Chase, MD, USA.
³ David H. Koch Center for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA.
⁴ Department of Dermatology, Stanford University, Stanford, CA, USA.
⁵ Department of Systems Biology, Columbia University, New York, NY, USA.
⁶ Department of Molecular Pharmacology and Therapeutics, Columbia University, New York, NY, USA.
⁷ Division of Gastroenterology, Massachusetts General Hospital, Boston, MA, USA.
⁸ Broad Institute of MIT and Harvard, Cambridge, MA, USA.
⁹ Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA, USA.
¹⁰ Center for Computational Biology, University of California, Berkeley, Berkeley, CA, USA.
¹¹ Department of Electrical Engineering and Computer Sciences, University of California, Berkeley, Berkeley, CA, USA.
¹² Harvard Society of Fellows, Harvard University, Cambridge, MA, USA.
¹³ Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA, USA.
¹⁴ Department of Physics, Harvard University, Cambridge, MA, USA.
¹⁵ Department of Systems Immunology, Weizmann Institute of Science, Rehovot, Israel.
¹⁶ Department of Biology, Massachusetts Institute of Technology, Cambridge, MA, USA.

^# Contributed equally.

PMID: 40705858
DOI: 10.1126/science.adx3800

High-resolution spatial mapping of cell state and lineage dynamics in vivo with PEtracer

Luke W Koblan et al. Science. 2025.

. 2025 Oct 16;390(6770):eadx3800.

doi: 10.1126/science.adx3800. Epub 2025 Oct 16.

Authors

Affiliations

¹ Whitehead Institute for Biomedical Research, Cambridge, MA, USA.
² Howard Hughes Medical Institute, Chevy Chase, MD, USA.
³ David H. Koch Center for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA.
⁴ Department of Dermatology, Stanford University, Stanford, CA, USA.
⁵ Department of Systems Biology, Columbia University, New York, NY, USA.
⁶ Department of Molecular Pharmacology and Therapeutics, Columbia University, New York, NY, USA.
⁷ Division of Gastroenterology, Massachusetts General Hospital, Boston, MA, USA.
⁸ Broad Institute of MIT and Harvard, Cambridge, MA, USA.
⁹ Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA, USA.
¹⁰ Center for Computational Biology, University of California, Berkeley, Berkeley, CA, USA.
¹¹ Department of Electrical Engineering and Computer Sciences, University of California, Berkeley, Berkeley, CA, USA.
¹² Harvard Society of Fellows, Harvard University, Cambridge, MA, USA.
¹³ Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA, USA.
¹⁴ Department of Physics, Harvard University, Cambridge, MA, USA.
¹⁵ Department of Systems Immunology, Weizmann Institute of Science, Rehovot, Israel.
¹⁶ Department of Biology, Massachusetts Institute of Technology, Cambridge, MA, USA.

^# Contributed equally.

PMID: 40705858
DOI: 10.1126/science.adx3800

Abstract

Charting the spatiotemporal dynamics of cell fate determination in development and disease is a long-standing objective in biology. Here, we present the design, development, and extensive validation of PEtracer, a prime editing (PE)-based, evolving lineage tracing technology compatible with both single-cell sequencing and multimodal imaging methodologies, created to jointly profile cell state and lineage in dissociated cells or while preserving cellular context in tissues with high spatial resolution. Using PEtracer coupled with MERFISH spatial transcriptomic profiling in a syngeneic mouse model of tumor metastasis, we reconstructed the growth of individually seeded tumors in vivo and uncovered distinct modules of cell-intrinsic and -extrinsic factors that coordinate tumor growth. More generally, PEtracer enables systematic characterization of cell state and lineage relationships in intact tissues over biologically relevant temporal and spatial scales.

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High-resolution spatial mapping of cell state and lineage dynamics in vivo with PEtracer.
Koblan LW, Yost KE, Zheng P, Colgan WN, Jones MG, Yang D, Kumar A, Sandhu J, Schnell A, Sun D, Ergen C, Saunders RA, Zhuang X, Allen WE, Yosef N, Weissman JS. Koblan LW, et al. bioRxiv [Preprint]. 2025 Jun 15:2025.06.15.659774. doi: 10.1101/2025.06.15.659774. bioRxiv. 2025. Update in: Science. 2025 Oct 16;390(6770):eadx3800. doi: 10.1126/science.adx3800. PMID: 40661400 Free PMC article. Updated. Preprint.

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High-resolution spatial mapping of cell state and lineage dynamics in vivo with PEtracer

Affiliations

High-resolution spatial mapping of cell state and lineage dynamics in vivo with PEtracer

Authors

Affiliations

Abstract

Update of

MeSH terms

Grants and funding

LinkOut - more resources

Full Text Sources

Molecular Biology Databases

Research Materials