This week in the PNAS Early Edition, researchers at the Washington University School of Medicine show that LRP6 silencing in breast cancer cells reduces Wnt signaling, cell proliferation, and tumor growth. Their results suggest that an LRP6 antagonist, Mesd, is a promising antitumor agent and potential therapeutic target for breast cancer subtypes with Wnt activation at the cell surface.
Also, Jia Qian Wu at Stanford University and colleagues report their discovery of previously unannotated transcripts and spliced isoforms specific to each stage of embryonic neural differentiation. They also say that splicing isoform diversity is highest in undifferentiated human embryonic stem cells, a finding they have termed “isoform specialization.” The authors write that their results provide insights into neural fate specification and progenitor cell identity maintenance, among other things.
Researchers describe their determination that NKp65 and KACL facilitate dedicated immune recognition of human keratinocytes. NKp65, when engaged by KACL, stimulates NK cytotoxicity and the release of proinflammatory cytokines. The team writes that their study deciphers a “receptor-ligand system that may fulfill a dedicated function in the immunobiology of human skin.”
In this week’s issue of PNAS, an international research team reports that male and female preimplantation embryos could display sex-specific transcriptional regulation for one third of the actively expressed genes in bovine blastocysts. Using a DNA microarray comparison method, the team examined the gene expression patterns between male and female blastocysts; nearly one third of the transcripts identified sexual dimorphism. They then analyzed six genes using qPCR. The team posits that the sex chromosomes “impose an extensive transcriptional regulation upon autosomal genes.”
As part of the PNAS special feature on regenerative medicine, Fan Yang of MIT and international colleagues describe their engineering of human stem cells for enhanced angiogenesis. Yang et al. seeded scaffolds with vascular endothelial growth factor-expressing stem cells; this led to two-to-four-fold higher vessel densities after implantation, compared with cells transfected with VEGF using a commercial reagent, or controls. “Treated stem cells demonstrated markedly enhanced hVEGF production, cell viability, and engraftment into target tissues,” the authors write.