title: A rapid passage through a two-active-X-chromosome state accompanies the switch of imprinted X-inactivation patterns in mouse trophoblast stem cells.
abstract: BACKGROUND
  In female mice, while the presence of two-active X-chromosomes characterises pluripotency, it is not tolerated in most other cellular contexts. In particular, in the trophoblastic lineage, impairment of paternal X (X(P)) inactivation results in placental defects.
  
  
  RESULTS
  Here, we show that Trophoblast Stem (TS) cells can undergo a complete reversal of imprinted X-inactivation without detectable change in cell-type identity. This reversal occurs through a reactivation of the X(P) leading to TS clones showing two active Xs. Intriguingly, within such clones, all the cells rapidly and homogeneously either re-inactivate the X(P) or inactivate, de novo, the X(M).
  
  
  CONCLUSIONS
  This secondary non-random inactivation suggests that the two-active-X states in TS and in pluripotent contexts are epigenetically distinct. These observations also reveal a pronounced plasticity of the TS epigenome allowing TS cells to dramatically and accurately reprogram gene expression profiles. This plasticity may serve as a back-up system when X-linked mono-allelic gene expression is perturbed.
authors.affiliation: Mouse Molecular Genetics Laboratory, Pasteur Institute, 25 rue du Dr Roux, 75015 Paris, France.
authors.forename: Julie
authors.initials: J
authors.lastname: Prudhomme
authors.affiliation: Mouse Molecular Genetics Laboratory, Pasteur Institute, 25 rue du Dr Roux, 75015 Paris, France ; Epigenetics of Stem Cells Laboratory, Pasteur Institute, 25 rue du Dr Roux, 75015 Paris, France.
authors.forename: Agnès
authors.initials: A
authors.lastname: Dubois
authors.affiliation: Epigenetics of Stem Cells Laboratory, Pasteur Institute, 25 rue du Dr Roux, 75015 Paris, France.
authors.forename: Pablo
authors.initials: P
authors.lastname: Navarro
authors.affiliation: Mouse Molecular Genetics Laboratory, Pasteur Institute, 25 rue du Dr Roux, 75015 Paris, France.
authors.forename: Danielle
authors.initials: D
authors.lastname: Arnaud
authors.affiliation: Mouse Molecular Genetics Laboratory, Pasteur Institute, 25 rue du Dr Roux, 75015 Paris, France ; Dynamics of Epigenetic Regulation, EMBL Monterotondo, Adriano Buzzati-Traverso Campus, Via Ramarini 32, 00015 Monterotondo, Italy.
authors.forename: Philip
authors.initials: P
authors.lastname: Avner
authors.affiliation: Mouse Molecular Genetics Laboratory, Pasteur Institute, 25 rue du Dr Roux, 75015 Paris, France ; CNRS, UMR7216 Epigenetics and Cell Fate, 35 rue Hélène Brion, 75013 Paris, France.
authors.forename: Céline
authors.initials: C
authors.lastname: Morey
keywords: Epigenetic Reprogramming; Imprinted X-inactivation; Trophoblast Stem cells