In utero barcoding of mouse mesoderm reveals the clonal architecture of organ mesenchyme
- 1Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden
Abstract
The mesoderm coordinates organogenesis and generates the cardiovascular, visceral and musculoskeletal systems, yet in mammals this germ layer is difficult to access, impeding its genetic manipulation and study. Here, we establish embryonic day (E) 7.5 exocoelomic cavity nano-injection as a scalable route for selective genetic targeting of mouse mesoderm. Combining in utero lentiviral barcoding with single-cell and spatial transcriptomics, we reconstructed mesodermal and neural crest clonal relationships across >590,000 cells and 31,000 multicellular clones from E9.5-E10.5 embryos and E16.5 livers and hearts. In liver, capsular mesothelium was closely related to hepatic stellate cells, whereas fibroblast and vascular smooth muscle lineages diverged earlier. In heart, epicardium was clonally coupled to three spatially restricted mesenchymal sub-lineages but not to cardiomyocytes, and lineage tracing separated epicardial- and neural crest-derived populations within transcriptionally convergent valve mesenchyme. This approach enables Cre-independent manipulation of mammalian mesoderm and resolves organ mesenchyme development at clonal resolution.
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BibTeX
@misc{he2026utero,
title = {{In utero barcoding of mouse mesoderm reveals the clonal architecture of organ mesenchyme}},
author = {J. He and J. Lorentz and A. A. Corbat and S. Isaev and R. Mauron and S. De Haan and L. Belicova and J. Sun and B. Semsch and N. Van Hul and R. Tonoian and J. Wilson and U. Marklund and M. Martin and N. C. Henderson and J. Frisen and M. Ratz and P. V. Kharchenko and I. Adameyko and E. Lazar and J. Lundeberg and E. R. Andersson},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.22.752134},
url = {https://www.biorxiv.org/content/10.64898/2026.09.22.752134v1},
note = {CC BY-NC},
}
RIS
TY - UNPB
TI - In utero barcoding of mouse mesoderm reveals the clonal architecture of organ mesenchyme
AU - J. He
AU - J. Lorentz
AU - A. A. Corbat
AU - S. Isaev
AU - R. Mauron
AU - S. De Haan
AU - L. Belicova
AU - J. Sun
AU - B. Semsch
AU - N. Van Hul
AU - R. Tonoian
AU - J. Wilson
AU - U. Marklund
AU - M. Martin
AU - N. C. Henderson
AU - J. Frisen
AU - M. Ratz
AU - P. V. Kharchenko
AU - I. Adameyko
AU - E. Lazar
AU - J. Lundeberg
AU - E. R. Andersson
PY - 2026
DA - 2026/09/22
PB - bioRxiv
DO - 10.64898/2026.09.22.752134
UR - https://www.biorxiv.org/content/10.64898/2026.09.22.752134v1
AB - The mesoderm coordinates organogenesis and generates the cardiovascular, visceral and musculoskeletal systems, yet in mammals this germ layer is difficult to access, impeding its genetic manipulation and study. Here, we establish embryonic day (E) 7.5 exocoelomic cavity nano-injection as a scalable route for selective genetic targeting of mouse mesoderm. Combining in utero lentiviral barcoding with single-cell and spatial transcriptomics, we reconstructed mesodermal and neural crest clonal relationships across >590,000 cells and 31,000 multicellular clones from E9.5-E10.5 embryos and E16.5 livers and hearts. In liver, capsular mesothelium was closely related to hepatic stellate cells, whereas fibroblast and vascular smooth muscle lineages diverged earlier. In heart, epicardium was clonally coupled to three spatially restricted mesenchymal sub-lineages but not to cardiomyocytes, and lineage tracing separated epicardial- and neural crest-derived populations within transcriptionally convergent valve mesenchyme. This approach enables Cre-independent manipulation of mammalian mesoderm and resolves organ mesenchyme development at clonal resolution.
ER -