Peer-reviewedCC BYCell
Comprehensive lineage tracing maps the landscape of cell fate decisions in mouse embryogenesis
10 affiliations
- 1Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA; Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA; David H. Koch Center for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
- 2Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA; Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA; David H. Koch Center for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. Electronic address: [email protected]
- 3Department of Genetics, Yale Stem Cell Center, Yale School of Medicine, New Haven, CT 06519, USA
- 4Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA
- 5Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA; Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138, USA; Department of Physics, Harvard University, Cambridge, MA 02138, USA
- 6Max Planck Institute of Molecular Genetics, Max Planck Society, 14195 Berlin, Germany
- 7Department of Developmental Biology, Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, Stanford, CA 94305, USA
- 8Department of Systems Immunology, Weizmann Institute of Science, 7610001 Rehovot, Israel
- 9Department of Genetics, Yale Stem Cell Center, Yale School of Medicine, New Haven, CT 06519, USA; Max Planck Institute of Molecular Genetics, Max Planck Society, 14195 Berlin, Germany. Electronic address: [email protected]
- 10Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA; Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA; David H. Koch Center for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. Electronic address: [email protected]
Abstract
. Here, we use PEtracer to continuously install heritable genetic marks as cells divide, reconstructing lineage trees that resolve ~75% of cell divisions across >1.5 million cells from 16 mouse embryos collected at half-day intervals from E7.5-E10.0. We pair these trees with deep transcriptional profiling to chart the landscape of cell fate decisions during gastrulation and early organogenesis. Using these data, we quantify cell fate biases, restriction timing, progenitor pool sizes, and lineage relationships across the embryo, revealing strikingly reproducible lineage architecture across replicate embryos despite the regulative flexibility of mammalian development. We further show how lineage, spatial position, and signaling jointly determine fate outcomes and timing, with their relative influence varying by tissue. This dataset provides a quantitative framework for understanding cell fate specification and a lineage-resolved reference for generating and contextualizing developmental hypotheses at organismal scale.
Related
- Spatiotemporal lineage tracing reveals the dynamic spatial architecture of tumor growth and metastasis
- Evolving strategies for lineage tracing: Genetic markers, synthetic barcodes, and natural variants
- Clonal lineage tracing and parallel multiomics profiling reveal transcriptional heterogeneity induced by ARID1A deficiency
- BASELINE: a CRISPR base editing platform for mammalian-scale single-cell lineage tracing
- SciPhy: A Bayesian phylogenetic framework using sequential genetic lineage tracing data
BibTeX
@article{colgan2026comprehensive,
title = {{Comprehensive lineage tracing maps the landscape of cell fate decisions in mouse embryogenesis}},
author = {William N. Colgan and Luke W. Koblan and JoAnne Villagrana and Tien-Chi Jason Hou and Minming Wang and Gokul Gowri and Whitney Chandler and Leonardo A. Sepúlveda and Didar Ciftci and Karina Smolyar and Kathryn E. Yost and Alicia Young and Lars Wittler and Styliani Markoulaki and Kyle M. Loh and Xiaowei Zhuang and Nir Yosef and Zachary D. Smith and Jonathan S. Weissman},
journal = {Cell},
year = {2026},
month = oct,
doi = {10.1016/j.cell.2026.09.050},
url = {https://doi.org/10.1016/j.cell.2026.09.050},
note = {CC BY},
}
RIS
TY - JOUR
TI - Comprehensive lineage tracing maps the landscape of cell fate decisions in mouse embryogenesis
AU - William N. Colgan
AU - Luke W. Koblan
AU - JoAnne Villagrana
AU - Tien-Chi Jason Hou
AU - Minming Wang
AU - Gokul Gowri
AU - Whitney Chandler
AU - Leonardo A. Sepúlveda
AU - Didar Ciftci
AU - Karina Smolyar
AU - Kathryn E. Yost
AU - Alicia Young
AU - Lars Wittler
AU - Styliani Markoulaki
AU - Kyle M. Loh
AU - Xiaowei Zhuang
AU - Nir Yosef
AU - Zachary D. Smith
AU - Jonathan S. Weissman
PY - 2026
DA - 2026/10/01
JO - Cell
DO - 10.1016/j.cell.2026.09.050
UR - https://doi.org/10.1016/j.cell.2026.09.050
AB - . Here, we use PEtracer to continuously install heritable genetic marks as cells divide, reconstructing lineage trees that resolve ~75% of cell divisions across >1.5 million cells from 16 mouse embryos collected at half-day intervals from E7.5-E10.0. We pair these trees with deep transcriptional profiling to chart the landscape of cell fate decisions during gastrulation and early organogenesis. Using these data, we quantify cell fate biases, restriction timing, progenitor pool sizes, and lineage relationships across the embryo, revealing strikingly reproducible lineage architecture across replicate embryos despite the regulative flexibility of mammalian development. We further show how lineage, spatial position, and signaling jointly determine fate outcomes and timing, with their relative influence varying by tissue. This dataset provides a quantitative framework for understanding cell fate specification and a lineage-resolved reference for generating and contextualizing developmental hypotheses at organismal scale.
SN - 0092-8674
SN - 1097-4172
ER -