ENAGenomicsMultiomicsSantos lab, Eli and Edythe Broad Center of Regeneration Medicine, UCSFhttps://www.ebi.ac.uk/ena/browser/view/PRJNA152575Mus musculusxref:PubMed:22286172Pluripotent stem cells are derived from culture of early embryos or the germline, and can be induced by reprogramming of somatic cells. Barriers to reprogramming are expected to exist that stabilize the differentiated state and have tumor suppression functions. However, we have a limited understanding of what such barriers might be. To find novel barriers to reprogramming to pluripotency, we compared the transcriptional profiles of the mouse germline to pluripotent and somatic cells, in vivo and in vitro. There is a remarkable global expression of the transcriptional program for pluripotency in Primordial Germ Cells (PGCs). We identify parallels between PGCs reprogramming to pluripotency and human germ cell tumorigenesis, including the loss of LATS2, a tumor suppressor kinase of the Hippo pathway. We show that knockdown of LATS2 increases the efficiency of induction of pluripotency in human cells. LATS2 RNAi, unlike p53 RNAi, specifically enhances the generation of fully reprogrammed iPS cells without accelerating cell proliferation. We further show that LATS2 represses reprogramming in human cells by post-transcriptionally antagonizing TAZ but not YAP, two downstream effectors of the Hippo pathway. These results reveal transcriptional parallels between germ cell transformation and the generation of iPS cells, and indicate that the Hippo pathway constitutes a barrier to cellular reprogramming. Overall design: Mouse pluripotent cells isolated directly from embryos or cultured in vitro as stem cells were analyzed using Affymetrix expression microarrays, together with several non-pluripotent cell controls, in 2-6 replicates per sample.ENAMus musculus, Laboratory Mice., House, Mus, Laboratory, Swiss, Mus domesticus, mouse, Mus musculus domesticus, Swiss Mouse, mouse <Mus musculus>, Mouse, House Mice, Swiss Mice, house mouse, Mice, Laboratory Mouse, House Mouse, mice C57BL/6xCBA/CaJ hybrid, domesticus, Mus muscarisPreimplantation Embryo, pluriblastus senior, Laboratory, Mus domesticus, Stem Cells, mouse, early embryoblast, Preimplantation, Germ-Line Cell, ectoblast, Germ, Pluripotent, House Mouse, Cell, mice C57BL/6xCBA/CaJ hybrid, Germ Lines, Mus muscaris, Germ Line, Stem Cell, House, Mus, Blastocysts, Preimplantation Embryos, Embryos, Mus musculus domesticus, Gamete, Pluripotent Stem Cell, Germ Line Cells, Germ Cell, Pluripotent., blastocyst, Mice, pluriblast, Gametes, blastocystis, Mus musculus, Embryo, Germ-Line Cells, embryoblastus, Swiss, mice, epiblast, Swiss Mouse, primitive ectoderm, House Mice, Swiss Mice, blastula, Germ-Line, domesticus, Laboratory Mice, embryoblast, Cells, ICM, Mouse, house mouse, epiblastus, Laboratory Mouse, massa cellularis internafalseMus musculusTranscriptional profiling of mouse inner cell mass of the blastocyst, primordial germ cells and cultured pluripotent stem cells2025-09-242014-02-11PRJNA152575GSE354161009022286172