Volume 22, No 1, Jan 2012
ISSN: 1001-0602
EISSN: 1748-7838 2018
impact factor 17.848*
(Clarivate Analytics, 2019)
Volume 22 Issue 1, January 2012: 178-193
ORIGINAL ARTICLES
Defining the nature of human pluripotent stem cell progeny
Michaela Patterson1,3,*, David N. Chan1,3,*, Iris Ha1, Dana Case4, Yongyan Cui1, Ben Van Handel1,3, Hanna KA Mikkola1,2,3,4 and William E Lowry1,2,3,4
1Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, CA 90095, USA
2Jonsson Comprehensive Cancer Center, University of California, Los Angeles, Los Angeles, CA 90095, USA
3Eli and Edythe Broad Center for Stem Cell Research, University of California, Los Angeles, Los Angeles, CA 90095, USA
4Molecular Biology Institute, University of California, Los Angeles, Los Angeles, CA 90095, USA
Correspondence: William E Lowry,(blowry@ucla.edu)
While it is clear that human pluripotent stem cells (hPSCs) can differentiate to generate a panoply of various cell types, it is unknown how closely in vitro development mirrors that which occurs in vivo. To determine whether human embryonic stem cells (hESCs) and human-induced pluripotent stem cells (hiPSCs) make equivalent progeny, and whether either makes cells that are analogous to tissue-derived cells, we performed comprehensive transcriptome profiling of purified PSC derivatives and their tissue-derived counterparts. Expression profiling demonstrated that hESCs and hiPSCs make nearly identical progeny for the neural, hepatic, and mesenchymal lineages, and an absence of re-expression from exogenous reprogramming factors in hiPSC progeny. However, when compared to a tissue-derived counterpart, the progeny of both hESCs and hiPSCs maintained expression of a subset of genes normally associated with early mammalian development, regardless of the type of cell generated. While pluripotent genes (OCT4, SOX2, REX1, and NANOG) appeared to be silenced immediately upon differentiation from hPSCs, genes normally unique to early embryos (LIN28A, LIN28B, DPPA4, and others) were not fully silenced in hPSC derivatives. These data and evidence from expression patterns in early human fetal tissue (3-16 weeks of development) suggest that the differentiated progeny of hPSCs are reflective of very early human development (< 6 weeks). These findings provide support for the idea that hPSCs can serve as useful in vitro models of early human development, but also raise important issues for disease modeling and the clinical application of hPSC derivatives.
Cell Research (2012) 22:178-193. doi:10.1038/cr.2011.133; published online 16 August 2011
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