Cell Journal: Great Progress!Wang Jichang’s team collaborated to construct new totipotent stem cells

2022-07-21 0 By

Totipotent cells have a greater developmental potential than any other cell type, resulting in embryos and extra-embryonic tissues.Stable totipotent cell cultures and deciphering the regulation of totipotency are invaluable for understanding cell plasticity and lineage separation in early development.9 February 2022,In Cell Stem Cell, chemic-induced Chromatin Remodeling Reprograms mouse ESCs to is remodeled by Ji-chang Wang and Chuanbo SunTotipotent -like stem cells “, which promotes the transition from pluripotency to totipotency by means of remodeling the peri-centromere heterochromatin and reconstructing the totipotent specific H3K4me3 domain.In mice, only zygotes and 2C embryos are true totipotent cells that give rise to blastocysts.The blastocyst consists of an inner cell mass (ICM) and an exotrophoblast (TE), which further develop into embryos and exoembryonic tissues, respectively.In contrast, the more developmentally restricted pluripotent cells from ICM can only give rise to embryonic tissue.The transformation from totipotency to pluripotency is a dynamic nuclear remodeling process.In mouse fertilized eggs and 2C embryos, the region around the centromeres, consisting mainly of repeated major satellites (majSat), forms a constitutive pericentromeres heterochromatin (PCH) that surrounds the nucleolar precursor (NPB) and forms a characteristic ring structure.After totipotency exits (from the 4-cell [4C] embryonic stage), PCH aggregates to form a staining center.The atypical extensive H3K4me3 domain inherited from oocytes is also associated with nuclear remodeling during fertilization and zygotic genome activation (ZGA), but disappears rapidly after totipotency exits.These findings suggest that the plasticity and developmental capacity of totipotent and pluripotent cells are reflected in their characteristic tissue chromatin.In mice, murine endogenous retrovirus L (MERVL) is specifically reactivated in totipotent 2C blastomere, and its reactivation stimulates the expression of many 2C-specific genes, suggesting that merVL-controlled networks are critical for regulating totipotency.A reporter gene based on MERVL can be used to enrich rare MERVL+ cells in mouse embryonic stem cell (mESC) cultures.2CLC is a valuable in vitro model for illustrating the transition between totipotency and pluripotency.However, 2CLCs cannot be maintained in long-term culture, so establishing stable totipotent cell cultures remains a challenge.In particular, the question remains whether stable totipotent stem cells can be created from early embryos.In this study, the hypothesis was followed that chromatin remodeling is a key underlying mechanism determining the transition from pluripotency to totipotency and the maintenance of totipotency.This study performed a multiomics comparative analysis of mESC, 2CLC, and 2C embryos and used the data to design chemical screens to target potential disorders.This combination strategy enabled the researchers to create stable totipotent stem cell lines (TLSC).TLSCs differ from mESCs and 2CLCs, but are very similar to 2C embryos in terms of 2C specific molecular profiles and strong developmental potency.Thus, TLSCs represent a very valuable cell type for the study of totipotency and embryology.Paper links: https://www.cell.com/cell-stem-cell/fulltext/S1934-5909 (22), 00010-8 # % 20 source: iNature