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Series GSE123055 Query DataSets for GSE123055
Status Public on Mar 07, 2019
Title Formative transition of human naïve pluripotent stem cells
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Summary Human naïve pluripotent stem cells (PSC) share features with pre-implantation epiblast. They thus provide an unmatched opportunity for characterising the developmental programme of pluripotency in Homo sapiens. Here we confirm that naïve PSC do not respond directly to germ layer induction, but must first acquire competence. Capacitation for multi-lineage differentiation occurs without exogenous growth factor stimulation and is facilitated by inhibition of Wnt signalling. Whole transcriptome profiling during this formative transition highlights dynamic changes in gene expression, affecting many cellular properties, including metabolism and epithelialisation. Notably, naïve pluripotency factors are exchanged for post-implantation factors, but competent cells remain devoid of lineage primed transcription. The gradual pace of transition for human naïve PSC is consistent with the timespan of primate development from blastocyst to gastrulation. Transcriptome trajectory during in vitro capacitation of human naïve cells tracks the progression of epiblast during embryogenesis in Macaca fascicularis, but shows greater divergence from mouse development. Thus the formative transition of naïve PSC in a simple culture system may recapitulate essential and specific features of pluripotency dynamics during an inaccessible period of human embryogenesis.
 
Overall design 2 lines of human naïve pluripotent stem cells (embryo-derived HNES1 and chemically reset cR-H9-EOS) were cultured in N2B27 and 2uM XAV939 for 10 days. After that the cells were split into two conditions: N2B27 + 2uM XAV939 + 3ng/ml Activin A + 10ng/ml FGF2 (XAF), or E8 medium, for extended maintenance. The experiment was performed in biological triplicates for each cell line. RNAseq was performed with the cells on day 0, 1, 2, 3, 7, 10, when the cells were cultured in XAV939; and one time point after transfer to maintenance conditions, at not less than 22 days of culture from the start of the experiment. Conventional hES cell line H9-EOS, which was a parental line for the chemically reset cR-H9-EOS was used as a control (in biological triplicate).
 
Contributor(s) Smith AG, Rostovskaya M, Stirparo GG
Citation(s) 30944104
Submission date Nov 28, 2018
Last update date May 09, 2019
Contact name Giuliano Giuseppe Stirparo
E-mail(s) giulianostirparo@gmail.com
Organization name Cerevance ltd
Street address 418 Cambridge Science Park Milton Rd
City Cambridge
State/province Cambridgeshire
ZIP/Postal code CB4 0PZ
Country United Kingdom
 
Platforms (1)
GPL16791 Illumina HiSeq 2500 (Homo sapiens)
Samples (51)
GSM3494453 A0: HNES1 XAV939 d0
GSM3494454 A1: HNES1 XAV939 d1
GSM3494455 A2: HNES1 XAV939 d2
Relations
BioProject PRJNA507424
SRA SRP171042

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Supplementary file Size Download File type/resource
GSE123055_counts.txt.gz 2.1 Mb (ftp)(http) TXT
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Raw data are available in SRA
Processed data are available on Series record

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