No abstract

Autosomal dominant hereditary polycystic kidney disease (ADPKD) is the most common inherited kidney disease that causes end‐stage renal disease and kidney failure. Preimplantation genetic testing for monogenic (PGT‐M) can effectively prevent the transmission of genetic diseases from parents to the offspring before pregnancy. However, PGT‐M currently adopts the single nucleotide polymorphism (SNP) linkage analysis for embryo's pathogenic gene carrying status and linkage analysis requires proband of the family. Here we report a new PGT‐M strategy using single sperm SNP linkage analysis for male patient with sporadic ADPKD caused by de novo PKD1 mutation. We recruited five couples with male patient with ADPKD caused by de novo PKD1 mutation, and 39 embryos from six PGT‐M cycles were detected. The five couples had at least one embryo that does not carry the PKD1 mutation. Within these five couples, the accuracy of carrier status of embryos was confirmed by amniotic fluid gene detection of two couples and two couples successfully delivered healthy fetuses. Therefore, the new PGT‐M strategy of using single sperm SNP linkage analysis was proved to be feasible and effective for male patient with ADPKD caused by de novo PKD1 mutation.

Background: Oocyte maturation arrest is a disease that produces immature oocytes and cannot be mature after culturing in vitro, which leads to female primary infertility. We aimed to summarize nine representative patients in our center to retrospectively analyze the genetic variants and clinical characteristics of oocyte maturation arrest.Methods: This study examined and analyzed nine families with oocyte maturation arrest. Whole-exome sequencing (WES) of the probands was performed to detect the pathogenic variants. Sanger sequencing verified the WES findings in patients and available parents. ExAC database was used to search the variant frequency. The variants were assessed by pathogenicity and conservational property prediction analysis and according to the American College of Medical Genetics and Genomics (ACMG). Phenotypes of oocytes were evaluated by a light microscopy, and the phenotype-genotype correlation was also evaluated.Results: Nine pathogenic variants in five genes were detected in nine patients, of which three were novel variants, including PATL2 [c.1374A > G (p. Ile458Met)] and [1289-1291del TCC (p. Leu430del)] and ZP2 [c.1543C > T (p. Pro515Ser)]. Nine variants were predicted to be pathogenic, resulting in different types of oocyte maturation arrest and clinical phenotypes.Conclusion: Three novel pathogenic variants were identified, enabling the expansion of the gene variant spectrum. The related pathogenic mutations of the PATL2, TUBB8, and ZP1∼3 genes were highly suggestive of being causative of oocyte maturation arrest.

Acute pancreatitis (AP) often leads to a high incidence of cardiac injury, posing significant challenges in the treatment of severe AP and contributing to increased mortality rates. Mesenchymal stem cells (MSCs) release bioactive molecules that participate in various inflammatory diseases. Similarly, extracellular vesicles (EVs) secreted by MSCs have garnered extensive attention due to their comparable anti-inflammatory effects to MSCs and their potential to avoid risks associated with cell transplantation. Recently, the therapeutic potential of MSCs-EVs in various inflammatory diseases, including sepsis and AP, has gained increasing recognition. Although preclinical research on the utilization of MSCs-EVs in AP-induced cardiac injury is limited, several studies have demonstrated the positive effects of MSCs-EVs in regulating inflammation and immunity in sepsis-induced cardiac injury and cardiovascular diseases. Furthermore, clinical studies have been conducted on the therapeutic application of MSCs-EVs for some other diseases, wherein the contents of these EVs could be deliberately modified through prior modulation of MSCs. Consequently, we hypothesize that MSCs-EVs hold promise as a potential therapy for AP-induced cardiac injury. This paper aims to discuss this topic. However, additional research is essential to comprehensively elucidate the underlying mechanisms of MSCs-EVs in treating AP-induced cardiac injury, as well as to ascertain their safety and efficacy.

Recently, haploid embryonic stem cells (haESCs) have been established in many species and widely used in forward and reverse genetic screening. Differentiated haploid cell line types in mammals are lacking due to spontaneous diploidization during differentiation that compromises lineage-specific screens. Human embryonic stem cells are widely used in basic and preclinical research. In this work, we report that human haESCs in extended pluripotent culture medium showed more compact colonies, higher efficiency in neural differentiation, and higher stability in haploidy maintenance, which effectively facilitated the derivation of haNSCs. Human haploid neural stem cells (haNSCs) can be generated by differentiation and maintain haploidy and multipotency to neurons and glia in the long term in vitro. After PiggyBac transfection, there were multiple insertion sites in the haNSC genome and the insertion sites evenly spread across all chromosomes. This is the first human haploid somatic cell line with a complete genome, proliferative ability and neural differentiation potential, which provides cell resources for recessive inheritance and drug targeted screening.