Highlights d NMN supplementation restores NAD + levels in maternally aged oocytes d NMN increases the number of ovulated oocytes in aged mice d NMN enhances meiotic competency and fertilization ability of aged oocytes d NMN recovers mitochondrial function to suppress ROSinduced apoptosis in aged oocytes
Salt stress triggers the overdose accumulation of reactive oxygen species (ROS) in crop plants, leading to severe oxidative damage to living tissues. MicroRNAs (miRNAs) act as master regulators orchestrating the stress responsive regulatory networks as well as salt tolerance. However, the fundamental roles of miRNAs in modulating salt tolerance in cereal crops, especially in salt-triggered ROS scavenging remain largely unknown. Through small RNA sequencing, a salt-responsive miRNA, miR172 was identified in rice. Further, by generating the miR172-overexpression or MIR172 gene loss-of-function mutant lines, the biological significance of miR172 and its downstream signaling pathways related to salt tolerance were defined. We demonstrated that miR172 is a positive regulator of salt tolerance in both rice and wheat. More interestingly, miR172a and miR172b, but not miR172c or miR172d are involved in salt stress response, emphasizing the functional differentiation within miR172 family members. Further evidence uncovers a novel miR172/IDS1 regulatory module that functions as a crucial molecular rheostat in maintaining ROS homeostasis during salt stress, mainly through balancing the expression of a group of ROS-scavenging genes. Our findings establish a direct molecular link between miRNAs and detoxification response in cereal crops for improving salt tolerance.
SummaryOwing to their single genome, haploid cells are powerful to uncover unknown genes by performing genetic screening in mammals. However, no haploid cell line from an extraembryonic lineage has been achieved yet, which limits the application of haploid cells in placental genetic screening. Here, we show that overexpression of Cdx2 can convert haploid embryonic stem cells to trophoblast stem cells (TSCs). p53 deletion reduces diploidization during the conversion and guarantees the generation of haploid-induced TSCs (haiTSCs). haiTSCs not only share the same molecular characterization with trophoderm-derived TSCs but also possess multipotency to placental lineages in various procedures. In addition, haiTSCs can maintain haploidy in the long term, assisted by periodic sorting and with reliance on FGF4 and heparin. Finally, we perform piggyBac-mediated high-throughput mutation in haiTSCs and use them in trophoblast lineage genetic screening. Deep sequencing analysis and validation experiments prove that Htra1 is a blocker for spongiotrophoblast specification.
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