Early alteration of the self-renewal/differentiation threshold in trophoblast stem cells derived from mouse embryos after nuclear transfer

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.ydbio.2009.07.022 Byline: Maite Rielland (a)(b), Vincent Brochard (a)(b), Marie-Christine Lacroix (c)(d), Jean-Paul Renard (a)(b), Alice Jouneau (a)(b) Keywords: Trophoblast; Nuclear transfer; Reprogramming; Self-renewal; Stem cells; Embryo; Growth factors Abstract: Development after nuclear transfer (NT) is subjected to defects originating from both the epiblast and the trophoblast parts of the conceptus and is always accompanied by placentomegaly at term. Here we have investigated the origin of the reprogramming errors affecting the trophoblast lineage in mouse NT embryos. We show that trophoblast stem (TS) cells can be derived from NT embryos (ntTS cells) and used as an experimental in vitro model of trophoblast proliferation and differentiation. Strikingly, TS derivation is more efficient from NT embryos than from controls and ntTS cells exhibit a growth advantage over control TS cells under self-renewal conditions. While epiblast-produced growth factors Fgf4 and Activin exert a fine-tuned control on the balance between self-renewal and differentiation of control TS cells, ntTS cells exhibit a reduced dependency upon their micro-environment. Since the supply of growth factors is known do decrease at the onset of placental formation in vivo we propose that TS cells in NT embryos continue to self-renew during a longer period of time than in fertilized embryo. The resulting increased pool of progenitors could contribute to the enlarged extra-embryonic region observed in the early trophoblast of in vivo grown mouse NT blastocysts that results in placentomegaly. Author Affiliation: (a) INRA, UMR 1198 Biologie du Developpement et Reproduction, F-78352 Jouy en Josas, France (b) ENVA, F-94704 Maisons Alfort, France (c) INRA, UMR 1197 Neurobiologie de l'Olfaction et de la Prise Alimentaire, Recepteurs et Communication Chimique, Jouy en Josas, France (d) Universite Paris-Sud, UMR1197, Orsay, France Article History: Received 5 May 2009; Revised 12 June 2009; Accepted 9 July 2009