Spermiogenesis alterations in the absence of CTCF revealed by single cell RNA sequencing.

CTCF is an architectonic protein that organizes the genome inside the nucleus in almost all eukaryotic cells. There is evidence that CTCF plays a critical role during spermatogenesis as its depletion produces abnormal sperm and infertility. However, defects produced by its depletion throughout spermatogenesis have not been fully characterized. In this work, we performed single cell RNA sequencing in spermatogenic cells with and without CTCF. We uncovered defects in transcriptional programs that explain the severity of the damage in the produced sperm. In the early stages of spermatogenesis, transcriptional alterations are mild. As germ cells go through the specialization stage or spermiogenesis, transcriptional profiles become more altered. We found morphology defects in spermatids that support the alterations in their transcriptional profiles. Altogether, our study sheds light on the contribution of CTCF to the phenotype of male gametes and provides a fundamental description of its role at different stages of spermiogenesis.

Linking indirect effects of cytomegalovirus in transplantation to modulation of monocyte innate immune function.

Cytomegalovirus (CMV) is an important cause of morbidity and mortality in the immunocompromised host. In transplant recipients, a variety of clinically important "indirect effects" are attributed to immune modulation by CMV, including increased mortality from fungal disease, allograft dysfunction and rejection in solid organ transplantation, and graft-versus-host-disease in stem cell transplantation. Monocytes, key cellular targets of CMV, are permissive to primary, latent and reactivated CMV infection. Here, pairing unbiased bulk and single cell transcriptomics with functional analyses we demonstrate that human monocytes infected with CMV do not effectively phagocytose fungal pathogens, a functional deficit which occurs with decreased expression of fungal recognition receptors. Simultaneously, CMV-infected monocytes upregulate antiviral, pro-inflammatory chemokine, and inflammasome responses associated with allograft rejection and graft-versus-host disease. Our study demonstrates that CMV modulates both immunosuppressive and immunostimulatory monocyte phenotypes, explaining in part, its paradoxical "indirect effects" in transplantation. These data could provide innate immune targets for the stratification and treatment of CMV disease.