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Thowfeequ, S.* ; Fiorentino, J. ; Hu, D.* ; Solovey, M. ; Ruane, S.* ; Whitehead, M.* ; Zhou, F.* ; Godwin, J.* ; Mateo-Otero, Y.* ; Vanhaesebroeck, B.* ; Scialdone, A. ; Srinivas, S.*

An integrated approach identifies the molecular underpinnings of murine anterior visceral endoderm migration.

Dev. Cell 59, 2347-2363.e9 (2024)
Postprint DOI PMC
Open Access Hybrid
Creative Commons Lizenzvertrag
The anterior visceral endoderm (AVE) differs from the surrounding visceral endoderm (VE) in its migratory behavior and ability to restrict primitive streak formation to the opposite side of the mouse embryo. To characterize the molecular bases for the unique properties of the AVE, we combined single-cell RNA sequencing of the VE prior to and during AVE migration with phosphoproteomics, high-resolution live-imaging, and short-term lineage labeling and intervention. This identified the transient nature of the AVE with attenuation of "anteriorizing" gene expression as cells migrate and the emergence of heterogeneities in transcriptional states relative to the AVE's position. Using cell communication analysis, we identified the requirement of semaphorin signaling for normal AVE migration. Lattice light-sheet microscopy showed that Sema6D mutants have abnormalities in basal projections and migration speed. These findings point to a tight coupling between transcriptional state and position of the AVE and identify molecular controllers of AVE migration.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Anterior Visceral Endoderm ; Cell Migration ; Embryonic Patterning ; Mouse Embryogenesis ; Phosphoproteomics ; Semaphorin Signaling ; Single-cell Transcriptomics; Posterior Axis Formation; Cell-migration; Rna-seq; Contact Inhibition; Mouse; Semaphorins; Expression; Receptor; Heterogeneity; Specification
Language english
Publication Year 2024
HGF-reported in Year 2024
ISSN (print) / ISBN 1534-5807
e-ISSN 1878-1551
Journal Developmental Cell
Quellenangaben Volume: 59, Issue: 17, Pages: 2347-2363.e9 Article Number: , Supplement: ,
Publisher Elsevier
Publishing Place 50 Hampshire St, Floor 5, Cambridge, Ma 02139 Usa
Reviewing status Peer reviewed
Institute(s) Institute of Epigenetics and Stem Cells (IES)
Institute of Computational Biology (ICB)
Institute of Functional Epigenetics (IFE)
POF-Topic(s) 30204 - Cell Programming and Repair
30205 - Bioengineering and Digital Health
30203 - Molecular Targets and Therapies
Research field(s) Stem Cell and Neuroscience
Enabling and Novel Technologies
Helmholtz Diabetes Center
PSP Element(s) G-506290-001
G-554200-001
G-502800-001
Grants Wellcome
Helmholtz Association
BBSRC
EMBO Scientific Exchange
Joachim Herz Stiftung Add-on Fellowship for Interdisciplinary Life Science
DOI 10.1016/j.devcel.2024.05.014
WOS ID 001325497300001
PubMed ID 38843837
Erfassungsdatum 2024-06-18
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