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FGF, Insulin, and SMAD Signaling Cooperate for Avian Primordial Germ Cell Self-Renewal

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    Rights statement: This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). © 2015 The Authors. Published by Elsevier Inc.

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http://linkinghub.elsevier.com/retrieve/pii/S2213671115003057
Original languageEnglish
Pages (from-to)1171–1182
JournalStem Cell Reports
Volume5
Issue number6
DOIs
Publication statusPublished - 1 Nov 2015

Abstract

Precise self-renewal of the germ cell lineage is fundamental to fertility and reproductive success. The early precursors for the germ line- age, primordial germ cells (PGCs), survive and proliferate in several embryonic locations during their migration to the embryonic gonad. By elucidating the active signaling pathways in migratory PGCs in vivo, we were able to create culture conditions that reca- pitulate this embryonic germ cell environment. In defined medium conditions without feeder cells, the growth factors FGF2, insulin, and Activin A, signaling through their cognate-signaling pathways, were sufficient for self-renewal of germline-competent PGCs. Forced expression of constitutively active MEK1, AKT, and SMAD3 proteins could replace their respective upstream growth factors. Unexpectedly, we found that BMP4 could replace Activin A in non-clonal growth conditions. These defined medium conditions iden- tify the key molecular pathways required for PGC self-renewal and will facilitate efforts in biobanking of chicken genetic resources and genome editing.

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