In Science this week, a Japanese research team describes the generation of human reproductive cells entirely in vitro, marking a key technological advance in reproductive biology. While human pluripotent stem cells (hPSCs) have been induced into primordial germ cell-like cells (hPGCLCs), further differentiation into mature germ cells has never been achieved. The researchers, however, show that hPGCLCs differentiate progressively into oogonia-like cells during long-term in vitro culture in xenogeneic reconstituted ovaries with mouse embryonic ovarian somatic cells. The investigators find that the hPGCLC-derived oogonia undergo proper epigenetic reprogramming including genome-wide DNA methylation and imprint erasure, and "acquire an immediate precursory state for meiotic recombination," they write. "These findings establish the germline competence of hPSCs and provide a critical step toward human in vitro gametogenesis."
And in Science Translational Medicine, an international group of researchers discusses the hallmarks of successful cancer immunotherapy, which can be expensive and toxic, but highly effective in the right patient. They highlight the need for robust predictive biomarkers, and cite the importance of understanding the overall genomic configuration of malignant cells in addition to specific mutations that can compromise immune system responses. Additionally, "the type, density, localization, and functional orientation of the immune infiltrate have a prominent impact on anticancer immunity, as do features of the tumor microenvironment linked to the vasculature and stroma, and systemic factors including the composition of the gut microbiota," the authors write. Ultimately, however, the implementation of truly personalized immunotherapeutic protocols will require the development of "multiparametric assessments with superior informational value," they conclude.