Notch signaling is required for maintaining stem-cell features of neuroprogenitor cells derived from human embryonic stem cells

<p>Abstract</p> <p>Background</p> <p>Studies have provided important findings about the roles of Notch signaling in neural development. Unfortunately, however, most of these studies have investigated the neural stem cells (NSCs) of mice or other laboratory animals rather than humans, mainly owing to the difficulties associated with obtaining human brain samples. It prompted us to focus on neuroectodermal spheres (NESs) which are derived from human embryonic stem cell (hESC) and densely inhabited by NSCs. We here investigated the role of Notch signaling with the hESC-derived NESs.</p> <p>Results</p> <p>From hESCs, we derived NESs, the <it>in-vitro </it>version of brain-derived neurospheres. NES formation was confirmed by increased levels of various NSC marker genes and the emergence of rosette structures in which neuroprogenitors are known to reside. We found that Notch signaling, which maintains stem cell characteristics of <it>in-vivo</it>-derived neuroprogenitors, is active in these hESC-derived NESs, similar to their <it>in-vivo </it>counterpart. Expression levels of Notch signaling molecules such as NICD, DLLs, JAG1, HES1 and HES5 were increased in the NESs. Inhibition of the Notch signaling by a γ-secretase inhibitor reduced rosette structures, expression levels of NSC marker genes and proliferation potential in the NESs, and, if combined with withdrawal of growth factors, triggered differentiation toward neurons.</p> <p>Conclusion</p> <p>Our results indicate that the hESC-derived NESs, which share biochemical features with brain-derived neurospheres, maintain stem cell characteristics mainly through Notch signaling, which suggests that the hESC-derived NESs could be an <it>in-vitro </it>model for <it>in-vivo </it>neurogenesis.</p

Interleukin-2 induces the in vitro maturation of human pluripotent stem cell-derived intestinal organoids.

Human pluripotent stem cell (hPSC)-derived intestinal organoids (hIOs) form 3D structures organized into crypt and villus domains, making them an excellent in vitro model system for studying human intestinal development and disease. However, hPSC-derived hIOs still require in vivo maturation to fully recapitulate adult intestine, with the mechanism of maturation remaining elusive. Here, we show that the co-culture with human T lymphocytes induce the in vitro maturation of hIOs, and identify STAT3-activating interleukin-2 (IL-2) as the major factor inducing maturation. hIOs exposed to IL-2 closely mimic the adult intestinal epithelium and have comparable expression levels of mature intestinal markers, as well as increased intestine-specific functional activities. Even after in vivo engraftment, in vitro-matured hIOs retain their maturation status. The results of our study demonstrate that STAT3 signaling can induce the maturation of hIOs in vitro, thereby circumventing the need for animal models and in vivo maturation

The HIST1 Locus Escapes Reprogramming in Cloned Bovine Embryos

Epigenetic reprogramming is necessary in somatic cell nuclear transfer (SCNT) embryos in order to erase the differentiation-associated epigenetic marks of donor cells. However, such epigenetic memories often persist throughout the course of clonal development, thus decreasing cloning efficiency. Here, we explored reprogramming-refractory regions in bovine SCNT blastocyst transcriptomes. We observed that histone genes residing in the 1.5 Mb spanning the cow HIST1 cluster were coordinately downregulated in SCNT blastocysts. In contrast, both the nonhistone genes of this cluster, and histone genes elsewhere remained unaffected. This indicated that the downregulation was specific to HIST1 histone genes. We found that, after trichostatin A treatment, HIST1 histone genes were derepressed, and DNA methylation at their promoters was decreased to the level of in vitro fertilization embryos. Therefore, our results indicate that the reduced expression of HIST1 histone genes is a consequence of poor epigenetic reprogramming in SCNT blastocysts

Correction: Park et al. Effect of Particulate Matter 2.5 on Fetal Growth in Male and Preterm Infants through Oxidative Stress. <i>Antioxidants</i> 2023, <i>12</i>, 1916

In the original publication [...

Effect of Particulate Matter 2.5 on Fetal Growth in Male and Preterm Infants through Oxidative Stress

Particulate matter 2.5 (PM2.5) levels are associated with adverse pregnancy outcomes. In this retrospective cohort study, we examined whether the concentration of indoor PM2.5 affected pregnancy outcomes. Additionally, we evaluated biomarkers of pregnancy-related complications caused by fine dust. We collected clinical information and data based on residential addresses from the Air Korea database to assess PM2.5 exposure levels. As a multicenter prospective cohort study, we measured the indoor PM2.5 concentration and inflammatory and oxidative stress markers. The PM2.5 concentration of the low-birth-weight (LBW) delivery group was 27.21 μg/m3, which was significantly higher than that of the normal-birth-weight (NBW) group (26.23 μg/m3) (p = 0.02). When the newborns were divided by sex, the PM2.5 concentration of the LBW group was 27.89 μg/m3 in male infants, which was significantly higher than that of the NBW group (26.26 μg/m3) (p = 0.01). In the prospective study, 8-hydroxy-2-deoxyguanosine significantly increased in the high-concentration group (113.55 ng/mL, compared with 92.20 ng/mL in the low-concentration group); in the high-concentration group, the rates of preterm birth (PTB) and small size for gestational age significantly increased (p p = 0.01). This study showed an association between PM2.5, oxidative stress, and fetal growth, with the PTB group being more vulnerable

The introduction to air pollution on pregnancy outcome (APPO) study: a multicenter cohort study

Objective The air pollution on pregnancy outcome (APPO) study is a prospective hospital-based cohort study designed to investigate the maternal and fetal effects of a particulate matter with an aerodynamic below 10 μm (PM10) and PM2.5 (below 2.5 μm) exposure. This study aims to analyze a relationship between particulate matter and adverse pregnancy outcomes and to find related biomarkers and develop management guidelines. Methods About 1,200 pregnant women are recruited for 3 years (from January 2021 to December 2023) from seven university hospitals to investigate the effects of particulate matter on pregnancy complications and adverse pregnancy outcomes. We collect biological samples by 5 mL of maternal venous blood and 15 mL of urine in each trimester of pregnancy, and 5 mL of umbilical cord blood and 2×2×2 cm of placental tissue are collected after delivery. In addition, by applying PM10 and PM2.5 concentration values and time-activity patterns from the time weighted average model, the individual predicted exposure of air pollution for the pregnant women are obtained. Results The average exposure of PM10 and PM2.5 of the participants in the entire period of pregnancy, was exceeded the World Health Organization air quality guidelines (an annual level, PM10 >15 μg/m3, PM2.5 >5 μg/m3). Moreover, it was revealed that the PM concentration was increasing toward the 3rd trimester of pregnancy. Conclusion The APPO study will be able to identify the degree of exposure to air pollution in pregnant women and use it as basic data for estimating individual exposure to particulate matter. And the results of the APPO study will facilitate in the development of health management for pregnant women against air pollution