Describing the Stem Cell Potency: The Various Methods of Functional Assessment and In silico Diagnostics

Abstract

Stem cells are defined by their capabilities to self-renew and give rise to various types of differentiated cells depending on their potency. They are classified as pluripotent, multipotent, and unipotent as demonstrated through their potential to generate the variety of cell lineages. While pluripotent stem cells may give rise to all types of cells in an organism, Multipotent and Unipotent stem cells remain restricted to the particular tissue or lineages. The potency of these stem cells can be defined by using a number of functional assays along with the evaluation of various molecular markers. These molecular markers include diagnosis of transcriptional, epigenetic, and metabolic states of stem cells. Many reports are defining the particular set of different functional assays, and molecular marker used to demonstrate the developmental states and functional capacities of stem cells. The careful evaluation of all these methods could help in generating standard identifying procedures/markers for them.

Keywords: EpiBlast; EpiSCs; chimera; iPSCs; naïve; pluripotency; primed; teratoma.

Figure 1

Classification of various types of pluripotenct stem cells on the basis of their origin. Various types of pluripotent stem cells can be classified on the basis of their origin or source from where they are taken and this would directly define their self-renewing and differentiation potential. Pluripotency of stem cells is also regulated through their culture microenvironment and they are often named on the basis of their similarity to the various types of previously established PSCs e.g., ICM-like or ES-like PSCs. [Mouse (+), Human (+) indicates derivation of ESCs inthese mammals; Human(−) indicates non-derivation of post-implantation EPIsc in humans].

Figure 2

Molecular diagnostics for determination of Pluripotency. Various research groups have demonstrated the molecular markers especially TFs which essentially regulate the self-renewal and differentiation potential of PSCs. These factors either directly regulate renewal/ differentiation through their binding to the target gene and therefore regulating target gene expression; or they themselves get regulated and are the target for a number of other transcription regulating elements such as miTNA, Noncoding RNA, Histone modifiers. Various researchers have wisely used these factors as the marker to define the potential of any test cells as an alternate approach to the standard functional assays.

Figure 3

The Various functional assessment approaches for Pluripotency. The most stringent tests for the determination of pluripotent cells that includes the various functional assay that essentially rely on the capabilities of test pluripotent cell to self-renew and differentiate into all the three germ cell lineages including ectoderm, mesoderm, and endoderm as mentioned in the text. Some of these assays would also explore the ability of test cells to give rise the whole organism and give rise to a chimeric animal of desired characteristics.