Differentiation-defective phenotypes revealed by large-scale analyses of human pluripotent stem cells

TLDR

Controversy remains over whether hiPSCs differ from hESCs in molecular signatures and differentiation capacity. hiPSCs and hESCs share similar RNA expression and DNA methylation patterns, yet certain hiPSC clones exhibit persistent undifferentiated cells, teratoma formation, and elevated expression of specific endogenous retroviral genes, necessitating their removal before therapeutic use.

Abstract

Significance In the past few years, findings have been controversial in regard to whether human induced pluripotent stem cells (hiPSCs) are distinct from human embryonic stem cells (hESCs) in their molecular signatures and differentiation properties. In this study, hiPSCs and hESCs have overlapping variations in molecular signatures such as RNA expression and DNA methylation. However, some hiPSC clones retained a significant number of undifferentiated cells even after neural differentiation culture and formed teratoma when transplanted into mouse brains. These differentiation-defective hiPSC clones were marked by higher expression levels of several genes, including those expressed from long terminal repeats of specific human endogenous retroviruses. They need to be identified and eliminated prior to applications in regenerative medicine.