Single-cell roadmap of human gonadal development.

Gonadal development is a complex process that involves sex determination followed by divergent maturation into either testes or ovaries1. Historically, limited tissue accessibility, a lack of reliable in vitro models and critical differences between humans and mice have hampered our knowledge of human gonadogenesis, despite its importance in gonadal conditions and infertility. Here, we generated a comprehensive map of first- and second-trimester human gonads using a combination of single-cell and spatial transcriptomics, chromatin accessibility assays and fluorescent microscopy. We extracted human-specific regulatory programmes that control the development of germline and somatic cell lineages by profiling equivalent developmental stages in mice. In both species, we define the somatic cell states present at the time of sex specification, including the bipotent early supporting population that, in males, upregulates the testis-determining factor SRY and sPAX8s, a gonadal lineage located at the gonadal-mesonephric interface. In females, we resolve the cellular and molecular events that give rise to the first and second waves of granulosa cells that compartmentalize the developing ovary to modulate germ cell differentiation. In males, we identify human SIGLEC15+ and TREM2+ fetal testicular macrophages, which signal to somatic cells outside and inside the developing testis cords, respectively. This study provides a comprehensive spatiotemporal map of human and mouse gonadal differentiation, which can guide in vitro gonadogenesis

American Journal of Hematology / Allogeneic hematopoietic stem cell transplantation from unrelated donors is associated with higher infection rates in children with acute lymphoblastic leukemiaA prospective international multicenter trial on behalf of the BFMSG and the EBMTPDWP

Severe infections (SI) significantly impact on nonrelapse mortality after hematopoietic stem cell transplantation (HSCT). We assessed 432 children and adolescents with acute lymphoblastic leukemia (ALL) after total body irradiation based myeloablative HSCT within the multicenter ALLBFMSCT 2003 trial for SI grade 3 or higher according to common terminology criteria for adverse events. A total 172 patients experienced at least one SI. Transplantation from matched unrelated donors (MUD) was associated with any type of SI in the preengraftment period (hazard ratio [HR]: 2.57; P <.001), and with any SI between day +30 and+100 (HR: 2.91; P =.011). Bacterial (HR: 2.24; P =.041) and fungal infections (HR: 4.06; P =.057) occurred more often in the preengraftment phase and viral infections more often before day +30 (HR: 2.66; P =.007) or between day +30 and+100 (HR: 3.89; P =.002) after HSCT from MUD as compared to matched sibling donors. Chronic GvHD was an independent risk factor for any type of SI after day +100 (HR: 2.57; P <.002). We conclude that allogeneic HSCT from MUD in children and adolescents with pediatric ALL is associated with higher infection rates, which seems attributable to an intensified GvHD prophylaxis including serotherapy and methotrexate.(VLID)509852

Amygdala activation during reading of emotional adjectives—an advantage for pleasant content

This event-related functional magnetic resonance imaging (fMRI) study investigated brain activity elicited by emotional adjectives during silent reading without specific processing instructions. Fifteen healthy volunteers were asked to read a set of randomly presented high-arousing emotional (pleasant and unpleasant) and low-arousing neutral adjectives. Silent reading of emotional in contrast to neutral adjectives evoked enhanced activations in visual, limbic and prefrontal brain regions. In particular, reading pleasant adjectives produced a more robust activation pattern in the left amygdala and the left extrastriate visual cortex than did reading unpleasant or neutral adjectives. Moreover, extrastriate visual cortex and amygdala activity were significantly correlated during reading of pleasant adjectives. Furthermore, pleasant adjectives were better remembered than unpleasant and neutral adjectives in a surprise free recall test conducted after scanning. Thus, visual processing was biased towards pleasant words and involved the amygdala, underscoring recent theoretical views of a general role of the human amygdala in relevance detection for both pleasant and unpleasant stimuli. Results indicate preferential processing of pleasant information in healthy young adults and can be accounted for within the framework of appraisal theory