Comment[ArrayExpressAccession]	E-GEOD-35416
Public Release Date	2012-01-31					
Investigation Title	Transcriptional profiling of mouse inner cell mass of the blastocyst, primordial germ cells and cultured pluripotent stem cells					
Comment[Submitted Name]	Transcriptional profiling of mouse inner cell mass of the blastocyst, primordial germ cells and cultured pluripotent stem cells
Experiment Description	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. 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.					
Date of Experiment						
Term Source Name	EFO
Term Source Version						
Term Source File	http://www.ebi.ac.uk/efo/efo.owl					
Person Last Name	Ramalho-Santos	Ramalho-Santos	Qin			
Person First Name	Miguel	Miguel	Han			
Person Mid Initials						
Person Email	mrsantos@diabetes.ucsf.edu					
Person Affiliation	UCSF					
Person Phone	415-502-8543					
Person Fax	415-514-2346					
Person Address	Ob/Gyn, Eli and Edythe Broad Center, UCSF, 513 Parnassus Ave, HSW1201A, San Francisco, CA, USA					
Person Roles	submitter					
Person Roles Term Source REF						
Person Roles Term Accession Number						
Normalization Type						
Normalization Term Accession Number						
Normalization Term Source REF						
Replicate Type						
Replicate Term Accession Number						
Replicate Term Source REF						
Experimental Design						
Experimental Design Term Accession Number						
Experimental Design Term Source REF						
Quality Control Type						
Quality Control Term Accession Number						
Quality Control Term Source REF						
Protocol Name	P-GSE35416-1	P-GSE35416-5	P-GSE35416-4	P-GSE35416-2	P-GSE35416-3	P-GSE35416-6
Protocol Description	ID_REF = <br>VALUE = log2 RMA data	Standard Affymetrix scanning protocols	Standard Affymetrix hybridization protocols	total RNA was extracted with Qiagen RNeasy kit with in-column DNAse digestion.	mRNA was amplified using two-rounds of in vitro transcription, and lableled by incorporation of bio-UTP in the second round.	intensities of the Affymetrix CEL files were background subtracted, quantile normalized, and summarized for each probe set into a logarithm base two intensity value using the robust multi-array average method (RMA) implemented in the Affymetrix package. Subsequently we applied the mean center global adjustment to remove apparent batch effects across the experiments to facilitate between-experiment comparisons.
Protocol Software						
Protocol Hardware						
Protocol Contact						
Protocol Type	bioassay_data_transformation	image_aquisition	hybridization	nucleic_acid_extraction	labeling	feature_extraction
Protocol Term Source REF						
Protocol Term Accession Number						
Experimental Factor Name	SOURCE AGE	STRAIN OR LINE	CELL TYPE	SEX		
Experimental Factor Type	source age	strain or line	cell type	sex		
Experimental Factor Term Source REF						
Experimental Factor Term Accession Number						
Publication Title	Transcriptional analysis of pluripotency reveals the Hippo pathway as a barrier to reprogramming.					
Publication Author List	Qin H, Blaschke K, Wei G, Ohi Y, Blouin L, Qi Z, Yu J, Yeh RF, Hebrok M, Ramalho-Santos M					
PubMed ID	22286172					
Publication DOI	10.1093/hmg/dds023					
Publication Status						
Publication Status Term Source REF						
Publication Status Term Accession Number						
Comment[SecondaryAccession]	GSE35416					
Comment[GEOLastUpdateDate]	2012-06-06
Comment[AEExperimentType]	transcription profiling by array					
Comment[GEOReleaseDate]	2012-01-31
Comment[ArrayExpressSubmissionDate]	2012-01-30
SDRF File	E-GEOD-35416.sdrf.txt