Establishment of totipotency does not depend on Oct4A.
Oct4A is a core component of the regulatory network of pluripotent cells, and by itself can reprogram neural stem cells into pluripotent cells in mice and humans. However, its role in defining totipotency and inducing pluripotency during embryonic development is still unclear. We genetically eliminated maternal Oct4A using a Cre/loxP approach in mouse and found that the establishment of totipotency was not affected, as shown by the generation of live pups. After complete inactivation of both maternal and zygotic Oct4A expression, the embryos still formed Oct4-GFP- and Nanog-expressing inner cell masses, albeit non-pluripotent, indicating that Oct4A is not a determinant for the pluripotent cell lineage separation. Interestingly, Oct4A-deficient oocytes were able to reprogram fibroblasts into pluripotent cells. Our results clearly demonstrate that, in contrast to its role in the maintenance of pluripotency, maternal Oct4A is not crucial for either the establishment of totipotency in embryos, or the induction of pluripotency in somatic cells using oocytes.
Max Planck Institute for Molecular Biomedicine, Department of Cell and Developmental Biology, Röntgenstrasse 20, 48149 Münster, Germany.
Guangming
G
Wu
Dong
D
Han
Yu
Y
Gong
Vittorio
V
Sebastiano
Luca
L
Gentile
Nishant
N
Singhal
Kenjiro
K
Adachi
Gerrit
G
Fischedick
Claudia
C
Ortmeier
Martina
M
Sinn
Martina
M
Radstaak
Alexey
A
Tomilin
Hans R
HR
Schöler
D000818:Animals; D019070:Cell Lineage / Q000235:genetics; D002478:Cells, Cultured; D065150:Cellular Reprogramming / Q000235:genetics; D004622:Embryo, Mammalian; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism; D005260:Female; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D017930:Genes, Reporter; D049452:Green Fluorescent Proteins; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D000071317:Nanog Homeobox Protein; D050814:Octamer Transcription Factor-3 / Q000172:deficiency / Q000235:genetics*; D009865:Oocytes / Q000166:cytology / Q000378:metabolism*; D039904:Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism; D011247:Pregnancy; D020033:Protein Isoforms / Q000172:deficiency / Q000235:genetics; D015398:Signal Transduction; D039901:Totipotent Stem Cells / Q000166:cytology / Q000378:metabolism*
D018398:Homeodomain Proteins; D000071317:Nanog Homeobox Protein; C475540:Nanog protein, mouse; D050814:Octamer Transcription Factor-3; C494174:Pou5f1 protein, mouse; D020033:Protein Isoforms; D049452:Green Fluorescent Proteins