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Magaletta, M.E.* ; Lobo, M.* ; Kernfeld, E.M.* ; Aliee, H. ; Huey, J.D.* ; Parsons, T.J.* ; Theis, F.J. ; Maehr, R.*

Integration of single-cell transcriptomes and chromatin landscapes reveals regulatory programs driving pharyngeal organ development.

Nat. Commun. 13:457 (2022)

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Maldevelopment of the pharyngeal endoderm, an embryonic tissue critical for patterning of the pharyngeal region and ensuing organogenesis, ultimately contributes to several classes of human developmental syndromes and disorders. Such syndromes are characterized by a spectrum of phenotypes that currently cannot be fully explained by known mutations or genetic variants due to gaps in characterization of critical drivers of normal and dysfunctional development. Despite the disease-relevance of pharyngeal endoderm, we still lack a comprehensive and integrative view of the molecular basis and gene regulatory networks driving pharyngeal endoderm development. To close this gap, we apply transcriptomic and chromatin accessibility single-cell sequencing technologies to generate a multi-omic developmental resource spanning pharyngeal endoderm patterning to the emergence of organ-specific epithelia in the developing mouse embryo. We identify cell-type specific gene regulation, distill GRN models that define developing organ domains, and characterize the role of an immunodeficiency-associated forkhead box transcription factor.

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Publication type Article: Journal article

Document type Scientific Article

Corresponding Author

Keywords Pluripotent Stem-cells; Branching Morphogenesis; Expression; Gene; Thymus; Differentiation; Endoderm; Foxn1; Derivatives; Vertebrate

ISSN (print) / ISBN 2041-1723

e-ISSN 2041-1723

Journal Nature Communications

Quellenangaben Volume: 13, Issue: 1, Article Number: 457

Publisher Nature Publishing Group

Publishing Place London

Non-patent literature Publications

Reviewing status Peer reviewed

Institute(s) Institute of Computational Biology (ICB)

Grants T32 AI132152
U01DK104218
R01AI132963
U.S.Israel Binational Science Foundation
Helmholtz Association's Initiative and Networking Fund through sparse2big
Helmholtz Association's Initiative and Networking Fund through Helmholtz AI
Hypopara Research Foundation
University of Pennsylvania Orphan Disease Center