Derivation of Intermediate Pluripotent Stem Cells Amenable to Primordial Germ Cell Specification

Developments in pluripotency: a new formative state

“…General trends within this timespan include a gradual increase in DNA methylation levels and a gradual switch from naïve transcription factor (TF) expression towards formative TF expression, seemingly followed by a more immediate switch towards lineage-biased TF expression in primed EpiSCs. 3,6,8,9 Interestingly, based on discriminative features, the pluripotent states as reported in these studies could be categorized into a more naïve-like intermediate state and a more primed-like intermediate state, the latter including the fPSCs (Fig. 1).…”

“…In 2020, three other groups have reported the pioneering of 2D culture conditions which support stable in vitro derivation and maintenance of intermediate pluripotent embryonic states. 3,8,9 All these states show cell polarity, a transcriptome indicative of formative pluripotency and, as far as assayed, 8 glycolytic metabolism. Surprisingly, comparative analysis of the transcriptomic and epigenomic data generated by these groups 3,8,9 and in the current study 6 show that the intermediate pluripotent ESCs in each of the culture conditions resemble different time points in the naïve-to-primed transition, over a timespan ranging from approximately E5.0 to E6.5 6 (Fig.…”

“…In contrast to the naïve-like group, the primed-like intermediate cells (i) show a developmentally more advanced transcriptome; (ii) are not capable of re-converting to naïve pluripotency (as far as assayed); (iii) do not show germline transmission in vivo; and (iv) show X inactivation in female cells. 3,6,8,9 Altogether, these in vitro cell systems provide an excellent model to comprehensively characterize the dynamic molecular processes associated with developmental progression of embryonic cells throughout pluripotency, and to understand how lineage commitment is executed.…”

“…While it remains to be tested whether the culture conditions as pioneered by Wang et al 6 support derivation and/or maintenance of fPSCs in human, two recent studies have reported human intermediate-like pluripotent stem cells using other cell culture conditions. 8,9 However, due to challenges of functionally testing human pluripotent cells and of staging these by the use of in vivo embryonic epigenomic and transcriptomic features, it remains difficult to properly benchmark human pluripotent cells. But with their better potential to respond to directed differentiation as compared to other human pluripotent ESCs, the establishment of human fPSCs might have important implications for regenerative medicine.…”

Step by Step about Germ Cells Development in Canine

“…Human PGC-like proteins showed different key factors that regulate germ cell induction, diverting from mouse PGC-like cells. Recently, XPSCs from mice, horses, and humans showed that they could contribute to chimeras and create precursors to sperm and eggs in a culture dish [132]. Based on this principle, it is important to study different species of animals to understand the basic principles of germ cell formation and transition in mammals.…”