An early developmental role for miRNAs in the maintenance of extraembryonic stem cells in the mouse embryo.
The two first cell fate decisions taken in the mammalian embryo generate three distinct cell lineages: one embryonic, the epiblast, and two extraembryonic, the trophoblast and primitive endoderm. miRNAs are essential for early development, but it is not known if they are utilized in the same way in these three lineages. We find that in the pluripotent epiblast they inhibit apoptosis by blocking the expression of the proapoptotic protein Bcl2l11 (Bim) but play little role in the initiation of gastrulation. In contrast, in the trophectoderm, miRNAs maintain the trophoblast stem cell compartment by directly inhibiting expression of Cdkn1a (p21) and Cdkn1c (p57), and in the primitive endoderm, they prevent differentiation by maintaining ERK1/2 phosphorylation through blocking the expression of Mapk inhibitors. Therefore, we show that there are fundamental differences in how stem cells maintain their developmental potential in embryonic and extraembryonic tissues through miRNAs.
Spruce
Thomas
T
MRC Clinical Sciences Centre, Imperial College London, Hammersmith Hospital, UK.
Pernaute
Barbara
B
Di-Gregorio
Aida
A
Cobb
Bradley S
BS
Merkenschlager
Matthias
M
Manzanares
Miguel
M
Rodriguez
Tristan A
TA
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D019521:Body Patterning; D002453:Cell Cycle / Q000502:physiology; D002454:Cell Differentiation / Q000502:physiology; D002460:Cell Line; D019070:Cell Lineage; D049109:Cell Proliferation; D053487:DEAD-box RNA Helicases / Q000235:genetics / Q000378:metabolism; D004622:Embryo, Mammalian / Q000166:cytology* / Q000502:physiology*; D004722:Endoribonucleases / Q000235:genetics / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D020869:Gene Expression Profiling; D005855:Germ Layers / Q000033:anatomy & histology / Q000502:physiology; D006801:Humans; D020935:MAP Kinase Signaling System / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D043244:Ribonuclease III; D013234:Stem Cells / Q000166:cytology / Q000502:physiology*
D035683:MicroRNAs; D048049:Extracellular Signal-Regulated MAP Kinases; D004722:Endoribonucleases; C509781:Dicer1 protein, mouse; D043244:Ribonuclease III; D053487:DEAD-box RNA Helicases