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

Autor:	Thowfeequ S; Institute for Developmental and Regenerative Medicine, Department of Physiology, Anatomy and Genetics, University of Oxford, Old Road Campus, Roosevelt Drive, Oxford OX3 7TY, UK., Fiorentino J; Institute of Epigenetics and Stem Cells, Helmholtz Zentrum München, German Research Center for Environmental Health, Munich 81377, Germany; Institute of Functional Epigenetics, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg 85764, Germany; Institute of Computational Biology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg 85764, Germany; Center for Life Nano- & Neuro-Science, Istituto Italiano di Tecnologia, Rome 00161, Italy., Hu D; Institute for Developmental and Regenerative Medicine, Department of Physiology, Anatomy and Genetics, University of Oxford, Old Road Campus, Roosevelt Drive, Oxford OX3 7TY, UK., Solovey M; Institute of Epigenetics and Stem Cells, Helmholtz Zentrum München, German Research Center for Environmental Health, Munich 81377, Germany; Institute of Functional Epigenetics, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg 85764, Germany; Institute of Computational Biology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg 85764, Germany., Ruane S; Institute for Developmental and Regenerative Medicine, Department of Physiology, Anatomy and Genetics, University of Oxford, Old Road Campus, Roosevelt Drive, Oxford OX3 7TY, UK., Whitehead M; UCL Cancer Institute, University College London, London WC1E 6DD, UK., Zhou F; University of Texas Southwestern Medical Center, Dallas, TX 75390, USA., Godwin J; Institute for Developmental and Regenerative Medicine, Department of Physiology, Anatomy and Genetics, University of Oxford, Old Road Campus, Roosevelt Drive, Oxford OX3 7TY, UK., Mateo-Otero Y; Institute for Developmental and Regenerative Medicine, Department of Physiology, Anatomy and Genetics, University of Oxford, Old Road Campus, Roosevelt Drive, Oxford OX3 7TY, UK; Unit of Cell Biology, Department of Biology, University of Girona, Girona 17004, Spain., Vanhaesebroeck B; UCL Cancer Institute, University College London, London WC1E 6DD, UK., Scialdone A; Institute of Epigenetics and Stem Cells, Helmholtz Zentrum München, German Research Center for Environmental Health, Munich 81377, Germany; Institute of Functional Epigenetics, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg 85764, Germany; Institute of Computational Biology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg 85764, Germany. Electronic address: antonio.scialdone@helmholtz-munich.de., Srinivas S; Institute for Developmental and Regenerative Medicine, Department of Physiology, Anatomy and Genetics, University of Oxford, Old Road Campus, Roosevelt Drive, Oxford OX3 7TY, UK. Electronic address: shankar.srinivas@dpag.ox.ac.uk.
Jazyk:	angličtina
Zdroj:	Developmental cell [Dev Cell] 2024 Sep 09; Vol. 59 (17), pp. 2347-2363.e9. Date of Electronic Publication: 2024 Jun 05.
DOI:	10.1016/j.devcel.2024.05.014
Abstrakt:	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. Competing Interests: Declaration of interests The authors declare no competing interests. (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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