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Janssen, P.* ; Jocher, J.* ; Vieth, B.* ; Edenhofer, F.C.* ; Dietl, T. ; Térmeg, A.* ; Spurk, P.* ; Geuder, J.* ; Enard, W.* ; Hellmann, I.*

Identification and comparison of orthologous cell types from primate embryoid bodies shows limits of marker gene transferability.

eLife, DOI: 10.7554/elife.105398 (2025)
Publ. Version/Full Text Research data DOI
Open Access Gold
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The identification of cell types remains a major challenge. Even after a decade of single-cellRNA sequencing (scRNA-seq), reasonable cell type annotations almost always include manualnon-automated steps. The identification of orthologous cell types across species complicatesmatters even more, but at the same time strengthens the confidence in the assignment. Here,we generate and analyze a dataset consisting of embryoid bodies (EBs) derived from inducedpluripotent stem cells (iPSCs) of four primate species: humans, orangutans, cynomolgus, andrhesus macaques. This kind of data includes a continuum of developmental cell types,multiple batch effects (i.e. species and individuals) and uneven cell type compositions andhence poses many challenges. We developed a semi-automated computational pipelinecombining classification and marker based cluster annotation to identify orthologous celltypes across primates. This approach enabled the investigation of cross-species conservationof gene expression. Consistent with previous studies, our data confirm that broadly expressedgenes are more conserved than cell type-specific genes, raising the question how conserved -inherently cell type-specific - marker genes are. Our analyses reveal that human markergenes are less effective in macaques and vice versa, highlighting the limited transferability ofmarkers across species. Overall, our study advances the identification of orthologous celltypes across species, provides a well-curated cell type reference for future in vitro studies andinforms the transferability of marker genes across species.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Transferability ; Identification
ISSN (print) / ISBN 2050-084X
e-ISSN 2050-084X
Journal eLife
Publisher eLife Sciences Publications
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Computational Biology (ICB)