Pancreatic-Like Cells Derived From Mouse Embryonic Stem Cells Are Regulated by Pdx1 Involving the Notch Pathway

Autor: Wa, Zhong, Yu, Lai, Zhong-Sheng, Xia, Ying, Lin, Chu-Yan, Ni, Zhong, Yu, Jie-Yao, Li, Tao, Yu, Qi-Kui, Chen
Rok vydání: 2022
Předmět:
Zdroj: Pancreas. 51:330-337
ISSN: 1536-4828
0885-3177
DOI: 10.1097/mpa.0000000000002018
Popis: Embryonic stem cells (ESCs)-derived pancreatic precursor cells have great potential for pancreas repair. Expression of pancreatic duodenal homeobox 1 (Pdx1) in definitive endoderm (DE) cells is the premise that DE cells differentiate into pancreatic cells. To achieve the required number of Pdx1-expressing DE cells for cell transplantation therapy, a valid model must be established. Using this model, researchers investigated how Pdx1 regulates ESC differentiation into pancreatic cells.Tet-On inducible lentiviral vector encoding Pdx1 or mock vector was transduced into mouse ESC (ES-E14TG2a). The mouse ESCs were divided into 3 groups: control (ESC), mock vector (Pdx1 - -ESC), and vector encoding Pdx1 (Pdx1 + -ESC). All groups were separately cocultured with the DE cells sorted by immune beads containing CXCR-4 + (C-X-C chemokine receptor type-4) antibody. Doxycycline induced the expression of Pdx1 on the Pdx1 + -ESC cells. The markers of cell differentiation and Notch pathway were examined.Significantly increased expression levels of Ptf1a, CK19, and amylase on day (d) 3 and d7, Neuro-D1 on d10 and d14, Pax6 and insulin on d14, as well as Notch1, Notch2, Hes1, and Hes5 on d3 and thereafter declined on d14 were observed in Pdx1 + -ESC group.Pdx1 + -ESC could differentiate into pancreatic-like cells with involvement of the Notch pathway.
Databáze: OpenAIRE