Unbiased lineage tracing across the adipose organ decouples developmental origin from anatomical and transcriptomic identities
- 1Division of Molecular Cardiovascular Biology, The Heart Institute. Division of Developmental Biology. Center for Stem Cell and Organoid Medicine. Cincinnati Chi
Abstract
The developmental origins of individual adipose depots and whether embryonic lineage dictates adult function remain unresolved. Here, we apply in utero CRISPR-mediated barcoding lineage tracing to construct the first unbiased clonal map of adipose organ development in mice. The developmental hierarchy we uncover challenges several conventions. Remarkably, interscapular brown fat, used as the prototypical brown fat, is the most developmentally isolated brown fat; depots sharing Myf5/Pax3 lineage markers fail to cluster together; mesenteric white fat shares unexpected high clonal ancestry with brown fats despite a radically divergent transcriptome; and subcutaneous white adipose tissues converge transcriptomically despite distant developmental origins. These findings call for a reinterpretation of single-marker lineage tracing data across the adipose organ and propose that adipose depot identity is not solely encoded by embryonic lineage but is substantially shaped by the anatomical niche.
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BibTeX
@misc{inoue2026unbiased,
title = {{Unbiased lineage tracing across the adipose organ decouples developmental origin from anatomical and transcriptomic identities}},
author = {O. Inoue and A. Singh and M. Ginugu and C. Ahn and M. A. Secchi and S. J. Bowling and H.-W. Lim and J. Sanchez-Gurmaches},
howpublished = {bioRxiv},
year = {2026},
month = nov,
doi = {10.64898/2026.11.05.762308},
url = {https://www.biorxiv.org/content/10.64898/2026.11.05.762308v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Unbiased lineage tracing across the adipose organ decouples developmental origin from anatomical and transcriptomic identities
AU - O. Inoue
AU - A. Singh
AU - M. Ginugu
AU - C. Ahn
AU - M. A. Secchi
AU - S. J. Bowling
AU - H.-W. Lim
AU - J. Sanchez-Gurmaches
PY - 2026
DA - 2026/11/05
PB - bioRxiv
DO - 10.64898/2026.11.05.762308
UR - https://www.biorxiv.org/content/10.64898/2026.11.05.762308v1
AB - The developmental origins of individual adipose depots and whether embryonic lineage dictates adult function remain unresolved. Here, we apply in utero CRISPR-mediated barcoding lineage tracing to construct the first unbiased clonal map of adipose organ development in mice. The developmental hierarchy we uncover challenges several conventions. Remarkably, interscapular brown fat, used as the prototypical brown fat, is the most developmentally isolated brown fat; depots sharing Myf5/Pax3 lineage markers fail to cluster together; mesenteric white fat shares unexpected high clonal ancestry with brown fats despite a radically divergent transcriptome; and subcutaneous white adipose tissues converge transcriptomically despite distant developmental origins. These findings call for a reinterpretation of single-marker lineage tracing data across the adipose organ and propose that adipose depot identity is not solely encoded by embryonic lineage but is substantially shaped by the anatomical niche.
ER -