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Sarrach, S.* ; Huang, Y.* ; Niedermeyer, S.* ; Hachmeister, M.* ; Fischer, L.* ; Gille, S.* ; Pan, M.* ; Mack, B.* ; Kranz, G.* ; Libl, D.* ; Merl-Pham, J. ; Hauck, S.M. ; Paoluzzi Tomada, E.* ; Kieslinger, M. ; Jeremias, I. ; Scialdone, A. ; Gires, O.*

Spatiotemporal patterning of EpCAM is important for murine embryonic endo-And mesodermal differentiation.

Sci. Rep. 8:1801 (2018)
Verlagsversion Forschungsdaten DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
Epithelial cell adhesion molecule EpCAM is expressed in pluripotent embryonic stem cells (ESC) in vitro, but is repressed in differentiated cells, except epithelia and carcinomas. Molecular functions of EpCAM, possibly imposing such repression, were primarily studied in malignant cells and might not apply to non-pathologic differentiation. Here, we comprehensively describe timing and rationale for EpCAM regulation in early murine gastrulation and ESC differentiation using single cell RNA-sequencing datasets, in vivo and in vitro models including CRISPR-Cas9-engineered ESC-mutants. We demonstrate expression of EpCAM in inner cell mass, epiblast, primitive/visceral endoderm, and strict repression in the most primitive, nascent Flk1+ mesoderm progenitors at E7.0. Selective expression of EpCAM was confirmed at mid-gestation and perinatal stages. The rationale for strict patterning was studied in ESC differentiation. Gain/loss-of-function demonstrated supportive functions of EpCAM in achieving full pluripotency and guided endodermal differentiation, but repressive functions in mesodermal differentiation as exemplified with cardiomyocyte formation. We further identified embryonic Ras (ERas) as novel EpCAM interactor of EpCAM and an EpCAM/ERas/AKT axis that is instrumental in differentiation regulation. Hence, spatiotemporal patterning of EpCAM at the onset of gastrulation, resulting in early segregation of interdependent EpCAM+ endodermal and EpCAM-/vimentin+ mesodermal clusters represents a novel regulatory feature during ESC differentiation.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Cell Adhesion Molecule; Pluripotent Stem-cells; Ep-cam; Antigen Epcam; E-cadherin; Expression; Cardiomyocytes; Bodies; Proliferation; Organization
Sprache englisch
Veröffentlichungsjahr 2018
HGF-Berichtsjahr 2018
ISSN (print) / ISBN 2045-2322
e-ISSN 2045-2322
Zeitschrift Scientific Reports
Quellenangaben Band: 8, Heft: 1, Seiten: , Artikelnummer: 1801 Supplement: ,
Verlag Nature Publishing Group
Verlagsort London
Begutachtungsstatus Peer reviewed
Institut(e) CF Metabolomics & Proteomics (CF-MPC)
Research Unit Gene Vector (AGV)
Institute of Epigenetics and Stem Cells (IES)
POF Topic(s) 30203 - Molecular Targets and Therapies
30504 - Mechanisms of Genetic and Environmental Influences on Health and Disease
30204 - Cell Programming and Repair
Forschungsfeld(er) Enabling and Novel Technologies
Immune Response and Infection
Stem Cell and Neuroscience
PSP-Element(e) G-505700-001
G-501590-001
G-506290-001
DOI 10.1038/s41598-018-20131-8
WOS ID WOS:000423430400013
Scopus ID 85043343802
PubMed ID 29379062
Erfassungsdatum 2018-03-12
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