StemCellDB: the human pluripotent stem cell database at the National Institutes of Health

Abstract

Much of the excitement generated by induced pluripotent stem cell technology is concerned with the possibility of disease modeling as well as the potential for personalized cell therapy. However, to pursue this it is important to understand the 'normal' pluripotent state including its inherent variability. We have performed various molecular profiling assays for 21 hESC lines and 8 hiPSC lines to generate a comprehensive snapshot of the undifferentiated state of pluripotent stem cells. Analysis of the gene expression data revealed no iPSC-specific gene expression pattern in accordance with previous reports. We further compared cells, differentiated as embryoid bodies in 2 media proposed to initiate differentiation towards separate cell fates, as well as 20 adult tissues. From this analysis we have generated a gene list which defines pluripotency and establishes a baseline for the pluripotent state. Finally, we provide lists of genes enriched under both differentiation conditions which show the proposed bias toward independent cell fates.

Figure 1

(A) Covariance PCA scatterplot and (B) Pearson correlation heat map depicting 175 samples using log (base=2) transformed quantile normalized expression for 4482 gene probes per sample. Gene probes selected for use represent those not noise-biased, not processing-biased, not gender-biased that pass ANOVA under multiple comparison correction condition (P<0.05) using class as the factor, pass post-hoc testing for at least one pair-wise class comparison (Tukey HSD P<0.05) and pass a mean– difference criteria (≥1.75) for the same pair-wise class comparison having a Tukey HSD P<0.05.

Figure 2

A–D) eNorthern of pluripotency genes – A) POU5F1/Oct4; B) NANOG; C) NODAL; D) TDGF1; E–F) eNortherns of differentiation associated gene expression – E) PAX6; F) RAX; G) MYH6; H) TNNT2. Green = undifferentiated samples, red = EB_ecto; blue = EB_mesend.

Figure 3

A) The StemCellDB gene expression search engine. A casual user can search their gene of interest directly or a more experienced user can access all raw data deposited with NCBI GEO by using the GEO Submissions link on the sidebar. B) Returned search results. Pop-up menus for each probe allow a user to select the most informative probes for further examination. C) Data is available in several formats for instant viewing as a chart or for download.