Testicular somatic cell-like cells derived from embryonic stem cells induce differentiation of epiblasts into germ cells

Regeneration of the testis from pluripotent stem cells is a real challenge, reflecting the complexity of the interaction of germ cells and somatic cells. Here we report the generation of testicular somatic cell-like cells (TesLCs) including Sertoli cell-like cells (SCLCs) from mouse embryonic stem cells (ESCs) in xeno-free culture. We find that Nr5a1/SF1 is critical for interaction between SCLCs and PGCLCs. Intriguingly, co-culture of TesLCs with epiblast-like cells (EpiLCs), rather than PGCLCs, results in self-organised aggregates, or testicular organoids. In the organoid, EpiLCs differentiate into PGCLCs or gonocyte-like cells that are enclosed within a seminiferous tubule-like structure composed of SCLCs. Furthermore, conditioned medium prepared from TesLCs has a robust inducible activity to differentiate EpiLCs into PGCLCs. Our results demonstrate conditions for in vitro reconstitution of a testicular environment from ESCs and provide further insights into the generation of sperm entirely in xeno-free culture

Etiopathogenesis and pathophysiology of malaria

Malaria is a parasitic disease caused by Plasmodium protozoan parasites and transmitted by Anopheles mosquitoes. The disease is diffused in tropical areas, where it is associated with high morbidity and mortality. P. falciparum is the most dangerous species, mainly affecting young children. The parasite cycle occurs both in humans (asexual stages) and in mosquitoes (sexual stages). In humans, Plasmodium grows and multiplies within red blood cells using hemoglobin as essential source of nutrients and energy. However, this process generates toxic heme that the parasite aggregates into an insoluble inert biocrystal called hemozoin. This molecule sequesters in various organs (liver, spleen, and brain), potentially contributing to the development of malaria immunopathogenesis. Uncomplicated falciparum malaria clinical frame ranges from asymptomatic infection to classic symptoms such as fever, chills, sweating, headache, and muscle aches. However, malaria can also evolve into severe life-threatening complications, including cerebral malaria, severe anemia, respiratory distress, and acute renal failure