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Series GSE35416 Query DataSets for GSE35416
Status Public on Jan 31, 2012
Title Transcriptional profiling of mouse inner cell mass of the blastocyst, primordial germ cells and cultured pluripotent stem cells
Organism Mus musculus
Experiment type Expression profiling by array
Summary Pluripotent 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.
 
Contributor(s) Ramalho-Santos M, Qin H
Citation(s) 22286172
Submission date Jan 30, 2012
Last update date Feb 18, 2018
Contact name Miguel Ramalho-Santos
E-mail(s) mrsantos@diabetes.ucsf.edu
Organization name UCSF
Department Eli and Edythe Broad Center of Regeneration Medicine
Lab Santos lab
Street address 35 Medical Center Way
City San Francisco
State/province CA
ZIP/Postal code 94143
Country USA
 
Platforms (1)
GPL81 [MG_U74Av2] Affymetrix Murine Genome U74A Version 2 Array
Samples (34)
GSM867836 primordial germ cells mixed E11.5 biol rep 1
GSM867837 primordial germ cells mixed E11.5 biol rep 2
GSM867838 primordial germ cells mixed E11.5 biol rep 3
Relations
BioProject PRJNA152575

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Supplementary file Size Download File type/resource
GSE35416_RAW.tar 93.3 Mb (http)(custom) TAR (of CEL)
Processed data included within Sample table
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