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)
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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Publikationstyp
Artikel: Journalartikel
Dokumenttyp
Wissenschaftlicher Artikel
Typ der Hochschulschrift
Herausgeber
Schlagwörter
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
Keywords plus
Sprache
englisch
Veröffentlichungsjahr
2024
Prepublished im Jahr
0
HGF-Berichtsjahr
2024
ISSN (print) / ISBN
1534-5807
e-ISSN
1878-1551
ISBN
Bandtitel
Konferenztitel
Konferzenzdatum
Konferenzort
Konferenzband
Quellenangaben
Band: 59,
Heft: 17,
Seiten: 2347-2363.e9
Artikelnummer: ,
Supplement: ,
Reihe
Verlag
Elsevier
Verlagsort
50 Hampshire St, Floor 5, Cambridge, Ma 02139 Usa
Tag d. mündl. Prüfung
0000-00-00
Betreuer
Gutachter
Prüfer
Topic
Hochschule
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Veröffentlichungsdatum
0000-00-00
Anmeldedatum
0000-00-00
Anmelder/Inhaber
weitere Inhaber
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Priorität
Begutachtungsstatus
Peer reviewed
POF Topic(s)
30204 - Cell Programming and Repair
30205 - Bioengineering and Digital Health
30203 - Molecular Targets and Therapies
Forschungsfeld(er)
Stem Cell and Neuroscience
Enabling and Novel Technologies
Helmholtz Diabetes Center
PSP-Element(e)
G-506290-001
G-554200-001
G-502800-001
Förderungen
Wellcome
Helmholtz Association
BBSRC
EMBO Scientific Exchange
Joachim Herz Stiftung Add-on Fellowship for Interdisciplinary Life Science
Copyright
Erfassungsdatum
2024-06-18