title: Heterogeneities in Nanog Expression Drive Stable Commitment to Pluripotency in the Mouse Blastocyst.
abstract: The pluripotent epiblast (EPI) is the founder tissue of almost all somatic cells. EPI and primitive endoderm (PrE) progenitors arise from the inner cell mass (ICM) of the blastocyst-stage embryo. The EPI lineage is distinctly identified by its expression of pluripotency-associated factors. Many of these factors have been reported to exhibit dynamic fluctuations of expression in embryonic stem cell cultures. Whether these fluctuations correlating with ICM fate choice occur in vivo remains an open question. Using single-cell resolution quantitative imaging of a Nanog transcriptional reporter, we noted an irreversible commitment to EPI/PrE lineages in vivo. A period of apoptosis occurred concomitantly with ICM cell-fate choice, followed by a burst of EPI-specific cell proliferation. Transitions were occasionally observed from PrE-to-EPI, but not vice versa, suggesting that they might be regulated and not stochastic. We propose that the rapid timescale of early mammalian embryonic development prevents fluctuations in cell fate.
authors.affiliation: Developmental Biology Program, Sloan Kettering Institute, New York, NY 10065, USA.
authors.forename: Panagiotis
authors.initials: P
authors.lastname: Xenopoulos
authors.affiliation: Developmental Biology Program, Sloan Kettering Institute, New York, NY 10065, USA; Biochemistry, Cell and Molecular Biology Program, Weill Graduate School of Medical Sciences of Cornell University, New York, NY 10065, USA.
authors.forename: Minjung
authors.initials: M
authors.lastname: Kang
authors.affiliation: Laboratory of Cell Migration, Candiolo Cancer Institute - FPO, IRCCS, Candiolo, Torino 10060, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Puliafito
authors.affiliation: Department of Cell Biology, Duke University Medical Center, Durham, NC 27710, USA.
authors.forename: Stefano
authors.initials: S
authors.lastname: Di Talia
authors.affiliation: Developmental Biology Program, Sloan Kettering Institute, New York, NY 10065, USA. Electronic address: hadj@mskcc.org.
authors.forename: Anna-Katerina
authors.initials: AK
authors.lastname: Hadjantonakis