Innate lymphoid cells (ILCs) are abundant in mucosal tissues and involved in tissue homeostasis and barrier function. Although several ILC subsets have been identified, it is unknown if additional... Show moreInnate lymphoid cells (ILCs) are abundant in mucosal tissues and involved in tissue homeostasis and barrier function. Although several ILC subsets have been identified, it is unknown if additional heterogeneity exists, and their differentiation pathways remain largely unclear. We applied mass cytometry to analyze ILCs in the human fetal intestine and distinguished 34 distinct clusters through a t-SNE-based analysis. A lineage (Lin)-CD7+CD127-CD45RO+CD56+ population clustered between the CD127+ ILC and natural killer (NK) cell subsets, and expressed diverse levels of Eomes, T-bet, GATA3, and RORγt. By visualizing the dynamics of the t-SNE computation, we identified smooth phenotypic transitions from cells within the Lin-CD7+CD127-CD45RO+CD56+ cluster to both the NK cells and CD127+ ILCs, revealing potential differentiation trajectories. In functional differentiation assays, the Lin-CD7+CD127-CD45RO+CD56+CD8a- cells could develop into CD45RA+NK cells and CD127+RORγt+ ILC3-like cells. Thus, we identified a previously unknown intermediate innate subset that can differentiate into ILC3 and NK cells. Show less
Genetic mouse model (39,XO) for human Turner Syndrome (45,XO) harboring either a single maternally inherited (Xm) or paternally inherited (Xp) chromosome show a pronounced difference in survival... Show moreGenetic mouse model (39,XO) for human Turner Syndrome (45,XO) harboring either a single maternally inherited (Xm) or paternally inherited (Xp) chromosome show a pronounced difference in survival rate at term. However, a detailed comparison of XmO and XpO placentas to explain this difference is lacking. We aimed to investigate the morphological and molecular differences between XmO and XpO term mouse placentas. We observed that XpO placentas at term contained a significantly larger area of glycogen cells (GCs) in their outer zone, compared to XmO, XX and XY placentas. In addition, the outer zone of XpO placentas showed higher expression levels of lactate dehydrogenase (Ldha) than XmO, XX and XY placentas, suggestive of increased anaerobic glycolysis. In the labyrinth, we detected significantly lower expression level of trophectoderm (TE)-marker keratin 19 (Krt19) in XpO placentas than in XX placentas. The expression of other TE-markers was comparable as well as the area of TE-derived cells between XO and wild-type labyrinths. XpO placentas exhibited specific defects in the amount of GCs and glucose metabolism in the outer zone, suggestive of increased anaerobic glycolysis, as a consequence of having inherited a single Xp chromosome. In conclusion, the XpO genotype results in a more severe placental phenotype at term, with distinct abnormalities regarding glucose metabolism in the outer zone. Show less
Nigro, A. lo; Jaime-Soguero, A. de; Khoueiry, R.; Cho, D.S.; Ferlazzo, G.M.; Perini, I.; ... ; Verfaillie, C.M. 2017
