title: Evidence for self-maintaining pluripotent murine stem cells  in embryoid bodies.
abstract: Pluripotent stem cells have great potential for regenerative medicine; however, their clinical use is associated with a risk of tumor formation. We utilized pluripotent cells expressing green fluorescent protein and puromycin resistance under control of the Oct4 promoter to study the persistence of potential pluripotent cells under embryoid body (EB) culture conditions, which are commonly used to obtain organotypic cells. We found that i.) OCT4-expressing cells dramatically decrease during the first week of differentiation, ii.) the number of OCT4-expressing cells recovers from day 7 on, iii.) the OCT4-expressing cells are similar to embryonic stem cells grown in the presence of leukemia inhibitory factor LIF but express several markers associated with germ cell formation, such as DAZL and STRA-8 and iv.) the persistence of potentially pluripotent cells is independent of supportive cells in EBs. Finally, OCT4-expressing cells, isolated from EBs after 2-month of culture, were further maintained under feeder-free conditions in absence of LIF and continued to express OCT4 in 95 % of the population for at least 36 days. These findings point to an alternative state of stable OCT4 expression. In the frame of the landscape model of differentiation two attractors of pluripotency might be defined based on their different characteristics.
authors.forename: Wael A
authors.initials: WA
authors.lastname: Attia
authors.forename: Osama M
authors.initials: OM
authors.lastname: Abd El Aziz
authors.forename: Dimitry
authors.initials: D
authors.lastname: Spitkovsky
authors.forename: John A
authors.initials: JA
authors.lastname: Gaspar
authors.forename: Peter
authors.initials: P
authors.lastname: Dröge
authors.forename: Frank
authors.initials: F
authors.lastname: Suhr
authors.forename: Davood
authors.initials: D
authors.lastname: Sabour
authors.forename: Johannes
authors.initials: J
authors.lastname: Winkler
authors.forename: Kesavan
authors.initials: K
authors.lastname: Meganathan
authors.forename: Smita
authors.initials: S
authors.lastname: Jagtap
authors.forename: Markus
authors.initials: M
authors.lastname: Khalil
authors.forename: Jürgen
authors.initials: J
authors.lastname: Hescheler
authors.lastname: Konrad Brockmeier
authors.lastname: Agapios Sachinidis
authors.lastname: Kurt Pfannkuche
mesh_terms: D000818:Animals; D058732:Embryoid Bodies / Q000166:cytology* / Q000378:metabolism*; D051379:Mice; D050814:Octamer Transcription Factor-3 / Q000235:genetics / Q000378:metabolism; D039904:Pluripotent Stem Cells / Q000166:cytology* / Q000378:metabolism
chemical_list: D050814:Octamer Transcription Factor-3; C494174:Pou5f1 protein, mouse
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