Capturing Pluripotency and Beyond

Abstract

During the development of a multicellular organism, the specification of different cell lineages originates in a small group of pluripotent cells, the epiblasts, formed in the preimplantation embryo. The pluripotent epiblast is protected from premature differentiation until exposure to inductive cues in strictly controlled spatially and temporally organized patterns guiding fetus formation. Epiblasts cultured in vitro are embryonic stem cells (ESCs), which recapitulate the self-renewal and lineage specification properties of their endogenous counterparts. The characteristics of totipotency, although less understood than pluripotency, are becoming clearer. Recent studies have shown that a minor ESC subpopulation exhibits expanded developmental potential beyond pluripotency, displaying a characteristic reminiscent of two-cell embryo blastomeres (2CLCs). In addition, reprogramming both mouse and human ESCs in defined media can produce expanded/extended pluripotent stem cells (EPSCs) similar to but different from 2CLCs. Further, the molecular roadmaps driving the transition of various potency states have been clarified. These recent key findings will allow us to understand eutherian mammalian development by comparing the underlying differences between potency network components during development. Using the mouse as a paradigm and recent progress in human PSCs, we review the epiblast’s identity acquisition during embryogenesis and their ESC counterparts regarding their pluripotent fates and beyond.

Engineering a Computable Epiblast for in silico Modeling of Developmental Toxicity

“…RAR/RXR liganding suppresses FGF-signaling and triggers Nodal/LEFTY1/CER1 antagonists in the AVE, ultimately influencing mesodermal Hox gene specification through CDX. The pluripotent epiblast is protected from premature differentiation until exposure to inductive cues in strictly controlled spatially and temporally organized patterns guiding fetal formation [31]. This includes precocious ATRA, an endogenous regulator of the patterned Hox gene expression.…”

“…This suggests that when and where a cell exits the streak is of critical importance to determining its anatomical fate [30]. As such, cell position in the epiblast is a physical determinant of mesodermal patterning by setting the distance an individual epiblast cell must travel to reach the primitive streak [31].…”

The Impact of Long Noncoding RNAs in Tissue Regeneration and Senescence

“…These cells are well-known for their self-renewal and differentiation abilities [31], which enable the development and regeneration of organs and tissues [32]. Stem cells, including embryonic stem cells (derived from the inner cell mass of pre-implantation embryos) [33] and induced pluripotent stem cells (obtained from somatic cells through cell reprogramming) [34], can be permanently maintained in their pluripotent state in vitro, while preserving their ability to differentiate under appropriate signal inputs [35]. However, and although lncRNAs have been shown to impact the reprograming process [16,36], their use has important limitations.…”