The mesodermal and myogenic specification of hESCs depend on ZEB1 and are inhibited by ZEB2

• DOI: 10.1016/j.celrep.2023.113222
• Publication Date: 2023-10-11T03:37:21Z
• Authors: Chiara Ninfali; Laura Siles; Anna Esteve-Codina; Antonio Postigo
• Keywords: QH301-705.5; Human Embryonic Stem Cells; Zinc Finger E-box-Binding Homeobox 1; Cell Differentiation; Muscular Dystrophies; Activins; [SDV] Life Sciences [q-bio]; Mice; CP: Stem cell research; Transforming Growth Factor beta; Animals; Humans; Cell Lineage; CP: Developmental biology; Biology (General); Zinc Finger E-box Binding Homeobox 2

Human embryonic stem cells (hESCs) can differentiate into any cell lineage. Here, we report that ZEB1 and ZEB2 promote inhibit mesodermal-to-myogenic specification of hESCs, respectively. Knockdown and/or overexpression experiments ZEB1, ZEB2, or PAX7 in hESCs indicate is required for hESC Nodal/Activin-mediated mesodermal PAX7+ human myogenic progenitor (hMuP) generation, while inhibits these processes. downregulation induces neural markers, mesodermal/myogenic markers. Mechanistically, binds to transcriptionally activates the promoter, promoter OTX2 marker. Transplanting knocked down hMuPs muscles a muscular dystrophy mouse model, showing hMuP engraftment generation dystrophin-positive myofibers depend on are inhibited by ZEB2. The model results suggest expression downregulating may also enhance regenerative capacity therapy.