Intergenerational Genetic Studies Of Chronic Social Defeat Stress And The Establishment And Culture Of Primate XEN Cells

Objective: Study of intergenerational transmission of paternal chronic social defeat stress.Methods: Adult male C57B/J mice were used as to establish the posttraumatic stress disorder(PDST)model by chronic social defeat stress.Next,the anxiety-like behaviors were detected by open field,elevated plus maze,sucrose preference and forced swim test.Then the social ranks of animals were determined using the tube test and the warm spot test.Results: The anxiety and depression-like behavioral abnormalities of adult male PDST C57 mice after chronic social defeat stress could be transmitted to the F1 generation with gender differences.Conclusion: The gender difference of some abnormal behaviors derived from paternal chronic social defeat stress may exists in F1 progenyThere are well-established systems for obtaining various types of stem cell lines from pre-implantation or post-implantation embryos including: embryonic stem cell line(ES),ectodermal stem cell line(EPI),extraembryonic endoderm stem cell line(XEN)and the trophoblastic stem cell line(TS).Mouse XEN cell lines can be constructed by directly culturing mouse embryos,ES cells overexpressing corresponding endoderm markers(GATA6,GATA4,SOX17,etc.)or culture conditions by adding RA and Act A induction and reprogramming.However,in the early studies,the obtained mouse XEN had weak self-renewal ability,and the cell state was unstable and could only be maintained for a short time.As the research progressed,it was found that the maintenance of mouse XEN cells also requires cell growth factors to maintain their dryness and proliferation.Recent studies have found that XEN cells of previously obtained mice express the corresponding endoderm Marker(GATA6,GATA4,SOX17,etc.),but do not express or underexpress pluripotency markers.The XEN cells obtained by the latest culture system expressed inner cell cluster markers(OCT4 and Rex1),and the expression levels of some pluripotent markers and GATA6 and IHH were much higher than those of the original XEN,and were named PXEN.PXEN transcriptome expression is similar to Pr E.And PXEN can be converted to XEN,but XEN cannot be converted to PXEN.Therefore,the mouse original XEN cell line can now be stably obtained.However,there is currently no stable system for establishing primate XEN cell lines,which seriously hinders the depth and breadth of research on embryo development.We constructed XEN cell lines with primate cynomolgus embryos based on the established conditions of mouse XEN.Through conditional exploration and optimization,we are now able to stably obtain the PXEN cell line of cynomolgus monkeys.Functional identification can differentiate into parietal endoderm(PE)and yolk sac endoderm(YE).