Multivariate meta-analysis reveals global transcriptomic signatures underlying distinct human naive-like pluripotent states

PLoS One. 2021 May 13;16(5):e0251461. doi: 10.1371/journal.pone.0251461. eCollection 2021.

Abstract

The ground or naive pluripotent state of human pluripotent stem cells (hPSCs), which was initially established in mouse embryonic stem cells (mESCs), is an emerging and tentative concept. To verify this vital concept in hPSCs, we performed a multivariate meta-analysis of major hPSC datasets via the combined analytic powers of percentile normalization, principal component analysis (PCA), t-distributed stochastic neighbor embedding (t-SNE), and SC3 consensus clustering. This robust bioinformatics approach has significantly improved the predictive values of our meta-analysis. Accordingly, we revealed various similarities or dissimilarities between some naive-like hPSCs (NLPs) generated from different laboratories. Our analysis confirms some previous studies and provides new evidence concerning the existence of three distinct naive-like pluripotent states. Moreover, our study offers global transcriptomic markers that define diverse pluripotent states under various hPSC growth protocols.

Publication types

  • Meta-Analysis
  • Research Support, N.I.H., Intramural

MeSH terms

  • Cell Differentiation
  • Cell Proliferation
  • Genomics / methods*
  • Humans
  • Pluripotent Stem Cells / cytology
  • Pluripotent Stem Cells / metabolism*
  • Transcriptome*

Grants and funding

This work was supported by the Intramural Research Program of the National Institutes of Health (NIH) at the National Institute of Neurological Disorders and Stroke (NINDS).