Embryonic stem cells (ESCs) have the potential to differentiate into cells of all tissue types, as demonstrated by their capability to contribute to the development of all germ layers in chimeras and to form teratomas. Of interest, however, is the lack of evidence of gametogenic gonadal tissues within teratomas, such as testicular tubules or follicles. Although this may reflect the fact that in vivo germ cell development and subsequent gametogenesis are complex biological processes, the generation of putative primordial germ cells (PGCs) has been reported during the differentiation of mouse and human ESCs in in vitro systems. In addition, mouse ESCs can even lead to the development of putative gametes, but the efficiency of this process needs to be improved and the functionality of the gametes remains to be proven. Interest in the generation of fully functional gametes from ESCs lies in an experimental model fundamental to the study of reproductive biology, a potential unlimited source of oocytes as a reprogramming bioreactor, and perhaps even in therapeutic applications to overcome human reproductive problems.

Transcription factor (TF) proteins bind to DNA to regulate gene expression. Normally, accessibility to DNA is required for their function. However, in the nucleus the DNA is often inaccessible, wrapped around histone proteins in nucleosomes forming the chromatin.Pioneer TFs are thought to induce chromatin opening by recognizing their DNA binding sites on nucleosomes. For example, Oct4, a master regulator and inducer of stem cell pluripotency, binds to DNA in nucleosomes in a sequence specific manner. Here we reveal the structural dynamics of nucleosomes that mediate Oct4 binding. Nucleosome mobility and the amplitude of nucleosome motions such as breathing and twisting correlate with the number of Oct4 binding sites available. Moreover, the regions around the binding sites display higher local mobility. Probing different structures of Oct4-nucleosome complexes, we show that alternative configurations display stable protein-DNA interactions and are compatible with the DNA curvature and DNA-histone interactions.

Several studies have pointed to retinal involvement in COVID 19 disease, yet many questions remain regarding the ability of SARS CoV 2 to infect and replicate in retinal cells and its effects on the retina. Here we have used human stem cell derived retinal organoids to study retinal infection by the SARS CoV 2 virus. Indeed, SARS CoV 2 can infect and replicate in retinal organoids, as it is shown to infect different retinal lineages, such as retinal ganglion cells and photoreceptors. SARS CoV 2 infection of retinal organoids also induces the expression of several inflammatory genes, such as interleukin 33, a gene associated with acute COVID 19 disease and retinal degeneration. Finally, we show that the use of antibodies to block the ACE2 receptor significantly reduces SARS CoV 2 infection of retinal organoids, indicating that SARS CoV 2 infects retinal cells in an ACE2 dependent manner. These results suggest a retinal involvement in COVID 19 and emphasize the need to monitor retinal pathologies as potential sequelae of long COVID.