Comprehensive Lineage Tracing Maps the Landscape of Cell Fate Decisions in Mouse Embryogenesis

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Authors: William N. Colgan, Luke W. Koblan, JoAnne Villagrana, Tien-Chi Jason Hou, Minming Wang, Gokul Gowri, Whitney Chandler, Leonardo A. Sepúlveda, Didar Ciftci, Karina Smolyar, Alicia Young, Lars Wittler
+6 more Styliani Markoulaki, Kyle M. Loh, Xiaowei Zhuang, Nir Yosef, Zachary D. Smith, Jonathan S. Weissman
Cited by: 3
References: 133

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.

Fields of Study & Subjects

Single-cell and spatial transcriptomics Pluripotent Stem Cells Research Developmental Biology and Gene Regulation

Publication details

Journal / source
bioRxiv (Cold Spring Harbor Laboratory)
Publisher
openRxiv
Publication date
9 May 2026
Language
EN
Document type
Preprint