Pou5f3.3 is involved in establishment and maintenance of hematopoietic cells during Xenopus development.

Three POU family class V gene homologues are expressed in the development of Xenopus. In contrast to the expression of Pou5f3.1 and Pou5f3.2 in organogenesis, Pou5f3.3 is expressed during oogenesis in ovary. We investigated the expression and function of Pou5f3.3 in organogenesis of Xenopus laevis. RT-PCR and immunohistochemical analysis indicated that Pou5f3.3 was expressed in a small number of adult liver cells and blood cells. Immunocytochemical investigation proved that Bmi1, a marker for hematopoietic progenitor cells, was co-expressed in Pou5f3.3-expressing small spherical cells in the peripheral blood. In anemic induction by intraperitoneal injection of phenyl hydrazine, the number of Pou5f3.3-expressing cells significantly increased within 3 days after phenyl hydrazine injection. In CRISPR/Cas mutagenesis of Pou5f3.3, Bmi1-positive hematopoietic progenitor cell count decreased in the hematopoietic dorsal-lateral plate (DLP) region, resulting in a considerable reduction in peripheral blood cells. CRISPR/Cas-induced hematopoietic deficiency was completely rescued by Pou5f3.3 supplementation, but not by Pou5f3.1 or Pou5f3.2. Transplantation experiments using the H2B-GFP transgenic line demonstrated that DLP-derived Pou5f3.3-positive and Bmi1-positive cells were translocated into the liver and bone through the bloodstream. These results suggest that Pou5f3.3 plays an essential role in the establishment and maintenance of hematopoietic progenitor cells during Xenopus development.

Photoperiodic changes in hippocampal neurogenesis and plasma metabolomic profiles in relation to depression-like behavior in mice.

Photoperiod alters affective behaviors and brain neuroplasticity in several mammalian species. We addressed whether neurogenesis and signaling pathways of insulin-like growth factor-I (IGF-I), a key modulator of neuroplasticity, are regulated by photoperiod in C57BL/6 J mice, a putative model of seasonal affective disorder. We also examined the effects of photoperiod on plasma metabolomic profiles in relation to depression-like behavior to understand a possible linkage between peripheral metabolism and behavior. Mice that were maintained under long-day conditions (LD) exhibited a higher number of 5-bromo-2'-deoxyuridine-positive cells and higher levels of astrocyte marker in the dentate gyrus of the hippocampus compared to that of mice under short-day conditions (SD). Plasma IGF-I levels and levels/expression of IGF-I signaling molecules in the hippocampus (Brn-4, NeuroD1, and phospho-Akt) involved in neuronal proliferation and differentiation were higher in the mice under LD. Metabolome analysis using plasma of the mice under LD and SD identified several metabolites that were highly correlated with immobility in the forced swim test, a depression-like behavior. Negative correlations with behavior occurred in the levels of 23 metabolites, including metabolites related to neurogenesis and antidepressant-like effects of exercise, metabolites in the biosynthesis of arginine, and the occurrence of branched chain amino acids. Three metabolites had positive correlations with the behavior, including guanidinosuccinic acid, a neurotoxin. Taken together, photoperiodic responses of neurogenesis and neuro-glial organization in the hippocampus may be involved in photoperiodic alteration of depression-like behavior, mediated through multiple pathways, including IGF-I and peripheral metabolites.

Long Noncoding RNA POU3F3 and α-Synuclein in Plasma L1CAM Exosomes Combined with ß-Glucocerebrosidase Activity: Potential Predictors of Parkinson's Disease.

Long noncoding RNAs (lncRNAs) are implicated in the autophagic-lysosomal pathway (ALP) and are closely linked to Parkinson's disease (PD) pathology. ß-Glucocerebrosidase (GCase) has also been reported to be correlated with α-synuclein (α-syn) proteostasis. However, lncRNAs and α-syn in neural-derived L1CAM exosomes and GCase activity in the plasma of PD patients have not been studied. This study used an ultrasensitive methodology, fluorescence nanoparticle tracking analysis (NTA), to measure plasma L1CAM exosomes and Quanterix Simoa to measure α-syn concentrations in L1CAM exosomes. Eighty-five healthy controls and 93 PD patients were enrolled, and several scales were used to rate the severity of PD. Receiver operating characteristic (ROC) curves were applied to map the diagnostic accuracy of categorizing PD patients and healthy subjects. We found increased Linc-POU3F3 and α-syn concentrations in L1CAM exosomes and decreased GCase activity in PD patients compared with controls. The three biomarkers displayed obvious differences among PD patients based on gender, H-Y stage, and UPDRS-III distribution. Interestingly, Linc-POU3F3 was significantly positively correlated with α-syn in L1CAM exosomes and inversely correlated with GCase activity in PD patients. Significant correlations were observed among L1CAM exosomal Linc-POU3F3 levels, GCase activity, and PD severity, including motor/cognitive dysfunction. Additionally, the combination of Linc-POU3F3 and α-syn in L1CAM exosomes and GCase activity could discriminate PD patients from controls. These results suggest that L1CAM exosomal Linc-POU3F3, L1CAM exosomal α-syn, and GCase activity may shed light on the mechanism underlying the autophagic-lysosomal system in the pathogenesis of PD and could be used to assess the severity of PD.