The mek-1/erks signalling pathway is differentially involved in the self-renewal of early and late avian erythroid progenitor cells

ABSTRACT Making decisions between self-renewal and differentiation is a central ability of stem cells. Elucidation of molecular networks governing this decision is therefore of prime

importance. A model of choice to explore this question is represented by chicken erythroid progenitors, in which self-renewal versus differentiation as well as progenitor maturation are

regulated by external factor combinations. We used this system to study whether similar or different signalling pathways were involved in the self-renewal of early, immature or more mature

erythroid progenitors. We show that a transforming growth factor (TGF)-_α_-activated Ras/MEK-1/ERK1/2 pathway is strictly required for immature self-renewing cells but becomes fully

dispensable when those cells are induced to differentiate. Consequently, pharmacological inhibition of this pathway led to spontaneous differentiation, only dependent on the presence of

survival signals. Conversely, ectopic expression of a constitutive form of MEK-1 stimulates renewal and arrests differentiation process. Finally, we demonstrate that the ERK/MAPK signalling

pathway is required in early but not in late primary erythroid progenitors, which can be turned into each other by different growth factor combinations specifically driving their renewal. To

the best of our knowledge, this is the first description of a central role of ERK/MAPK signalling in regulating progenitor plasticity in the same cell type under different environmental

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customer support SIMILAR CONTENT BEING VIEWED BY OTHERS COOPERATIVE CONTRIBUTIONS OF THE _KLF1_ AND _KLF17_ GENES IN ZEBRAFISH PRIMITIVE ERYTHROPOIESIS Article Open access 10 August 2023

GENERATION AND TRAPPING OF A MESODERM BIASED STATE OF HUMAN PLURIPOTENCY Article Open access 05 October 2020 ESRRB GUIDES NAIVE PLURIPOTENT CELLS THROUGH THE FORMATIVE TRANSCRIPTIONAL

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AH, Stetler K, Higgins RR, Howard J, Dumont D, Berger SA and Ben-David Y . (2000). _Oncogene_, 19, 2296–2304. Download references ACKNOWLEDGEMENTS We thank all of those who are cited in the

‘Material and methods’ section for their generous gifts; Michèle Weiss for her assistance with FACS analysis; Edmund Derrington for manuscript corrections and all the members of the CGMC and

specially the ‘hematopoiesis subsection’ for their invaluable help in setting up things. The work in our laboratory is supported by the Ligue contre le cancer (Comité Départemental du

Rhône), the CNRS, the UCBL, the Région Rhône-Alpes (Programme Emergence), the Fondation de France and the Association pour la Recherche contre le Cancer. SD is a fellow from the Ligue contre

le cancer (Comité départemental de l'Yonne) and the Association pour la Recherche contre le Cancer. FD is a fellow from the EU RTN program ‘Hematopoiesis’ (contract

HPRN-CT-2000-00083). Work in the HB laboratory was supported by the above EU grant and by the Fonds zur Förderung der wissenschaftlichen Forschung Austria, (SFB 006). AUTHOR INFORMATION

AUTHORS AND AFFILIATIONS * Laboratoire ‘Signalisations et identités cellulaires’, Centre de Génétique Moléculaire et Cellulaire CNRS UMR 5534, Université Claude Bernard Lyon 1, bât Grégoire

Mendel Sébastien Dazy, Francesca Damiola, Nicolas Parisey & Olivier Gandrillon * 16 rue Dubois, Villeurbanne cedex, 69622, France Sébastien Dazy, Francesca Damiola, Nicolas Parisey &

 Olivier Gandrillon * Institute of Molecular Pathology, DrBohr-Gasse 7, Wien, A-1030, Austria Hartmut Beug Authors * Sébastien Dazy View author publications You can also search for this

author inPubMed Google Scholar * Francesca Damiola View author publications You can also search for this author inPubMed Google Scholar * Nicolas Parisey View author publications You can

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ARTICLE CITE THIS ARTICLE Dazy, S., Damiola, F., Parisey, N. _et al._ The MEK-1/ERKs signalling pathway is differentially involved in the self-renewal of early and late avian erythroid

progenitor cells. _Oncogene_ 22, 9205–9216 (2003). https://doi.org/10.1038/sj.onc.1207049 Download citation * Received: 05 May 2003 * Revised: 17 July 2003 * Accepted: 29 July 2003 *

Published: 18 December 2003 * Issue Date: 18 December 2003 * DOI: https://doi.org/10.1038/sj.onc.1207049 SHARE THIS ARTICLE Anyone you share the following link with will be able to read this

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KEYWORDS * MEK-1 * self-renewal * TGF-_α_ * erythropoiesis