Hallmarks of pluripotency

Abstract

Stem cells self-renew and generate specialized progeny through differentiation, but vary in the range of cells and tissues they generate, a property called developmental potency. Pluripotent stem cells produce all cells of an organism, while multipotent or unipotent stem cells regenerate only specific lineages or tissues. Defining stem-cell potency relies upon functional assays and diagnostic transcriptional, epigenetic and metabolic states. Here we describe functional and molecular hallmarks of pluripotent stem cells, propose a checklist for their evaluation, and illustrate how forensic genomics can validate their provenance.

An overview of mammalian pluripotency

“…However, several lines of evidence indicate that hESCs differ from mESCs and more closely resemble mEpiSCs (De Los Angeles et al, 2015). This has led to the notion that hESCs are primed, akin to mEpiSCs; however, such a comparison might be overly simplistic and it could be more useful to think of hESCs as a case apart.…”

“…Despite the success, however, the various culture conditions used to generate naïve hESCs have resulted in an inherent variability in the molecular signatures of the cells, thus making it difficult to compare naïve hESCs and mESCs (Huang et al, 2014). This has been further complicated by difficulties in developing proper in vivo functional assays that are able to validate the human naïve state (De Los Angeles et al, 2015;Wu and Izpisua Belmonte, 2015). Therefore, to date, the issue of whether human naïve pluripotency truly exists as it does in the mouse remains unresolved and continued research along this line is needed (Pera, 2014).…”

“…Gene expression profiles can also help to distinguish distinct PSC states. In addition, other molecular features, such as X chromosome status in female cells, differential usage of Oct4 enhancers and epigenetic features such as DNA and histone methylation also vary between different PSC types (De Los Angeles et al, 2015). Different PSC states can also be set apart by the preferential utilization of metabolic pathways involved in energy production and catabolic and anabolic processes (Sperber et al, 2015;Zhou et al, 2012).…”

Animal use for science in Europe

“…For cases that require in vivo data in this area, a pluripotency test method is available that does not require growth of teratomas in mice. This alternative approach is used still rarely, although it has the potential to reduce suffering, and it has a higher scientific validity (Li et al, 2015;De Los Angeles et al, 2015). This situation is exemplary for many areas of biomedical research, in which old and traditional animal experimentation is still performed, although suffering could be reduced, or the experiment may be entirely replaced.…”

Bioinformatic and Genomic Analyses of Cellular Reprogramming and Direct Lineage Conversion

“…Before cellular reprogramming became a common practice, a multitude of researchers were involved in using bioinformatic approaches to investigate the complex pluripotent state (reviewed in [22,32,67]). Microarray analysis was first utilized to perform transcriptional profiling of ES cells and to define the pluripotent network [72,80].…”