Chenze Xu1, Yichen Dai1, Ali Mohsin1, Haifeng Hang1,2, Yingping Zhuang1,2, Meijin Guo3,4,5. 1. State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai, 200237, People's Republic of China. 2. Engineering Research Centre of Processes System, Ministry of Education, East China University of Science and Technology, 130 Meilong Rd., Shanghai, 200237, China. 3. State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai, 200237, People's Republic of China. guo_mj@ecust.edu.cn. 4. Engineering Research Centre of Processes System, Ministry of Education, East China University of Science and Technology, 130 Meilong Rd., Shanghai, 200237, China. guo_mj@ecust.edu.cn. 5. Institute for Stem Cell and Regeneration, Chinese Academy of Sciences, Beijing, 100101, China. guo_mj@ecust.edu.cn.
Abstract
BACKGROUND: Embryonic Sertoli cells (eSCs) have been known for playing important roles in male reproductive development system. In current studies, eSCs were mainly generated from induced intermediate mesoderm. The deriving mechanism of eSCs has been unclear so far. Therefore, this work was aimed to reveal the molecular pathways during derivation of eSCs. METHODS: In this scenario, a differentiation model from mouse embryonic stem cells (mESCs) to eSCs was established through spatiotemporal control of 5 key factors, Wilms tumor 1 homolog (Wt1), GATA binding protein 4 (Gata4), nuclear receptor subfamily 5, group A, member 1 (Nr5a1, i.e., Sf1), SRY (sex determining region Y)-box 9 (Sox9), doublesex, and mab-3 related transcription factor 1 (Dmrt1). To investigate the molecular mechanism, these key factors were respectively manipulated through a light-switchable (light-on) system, tetracycline-switchable (Tet-on) system, and CRISPR/Cas9 knock out (KO) system. RESULTS: Via the established approach, some embryonic Sertoli-like cells (eSLCs) were induced from mESCs and formed ring-like or tubular-like structures. The key factors were respectively manipulated and revealed their roles in the derivation of these eSLCs. Based on these results, some molecular pathways were mapped during the development of coelomic epithelial somatic cells to eSCs. CONCLUSIONS: This differentiation model provided a high controllability of some key factors and brought a novel insight into the deriving mechanism of Sertoli cells.
BACKGROUND:Embryonic Sertoli cells (eSCs) have been known for playing important roles in male reproductive development system. In current studies, eSCs were mainly generated from induced intermediate mesoderm. The deriving mechanism of eSCs has been unclear so far. Therefore, this work was aimed to reveal the molecular pathways during derivation of eSCs. METHODS: In this scenario, a differentiation model from mouse embryonic stem cells (mESCs) to eSCs was established through spatiotemporal control of 5 key factors, Wilms tumor 1 homolog (Wt1), GATA binding protein 4 (Gata4), nuclear receptor subfamily 5, group A, member 1 (Nr5a1, i.e., Sf1), SRY (sex determining region Y)-box 9 (Sox9), doublesex, and mab-3 related transcription factor 1 (Dmrt1). To investigate the molecular mechanism, these key factors were respectively manipulated through a light-switchable (light-on) system, tetracycline-switchable (Tet-on) system, and CRISPR/Cas9 knock out (KO) system. RESULTS: Via the established approach, some embryonic Sertoli-like cells (eSLCs) were induced from mESCs and formed ring-like or tubular-like structures. The key factors were respectively manipulated and revealed their roles in the derivation of these eSLCs. Based on these results, some molecular pathways were mapped during the development of coelomic epithelial somatic cells to eSCs. CONCLUSIONS: This differentiation model provided a high controllability of some key factors and brought a novel insight into the deriving mechanism of Sertoli cells.
Authors: Anna Minkina; Clinton K Matson; Robin E Lindeman; Norbert B Ghyselinck; Vivian J Bardwell; David Zarkower Journal: Dev Cell Date: 2014-05-22 Impact factor: 12.270
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Authors: Nick Warr; Gwenn-Aël Carre; Pam Siggers; Jessica Vitos Faleato; Rachel Brixey; Madeleine Pope; Debora Bogani; Melissa Childers; Sara Wells; Cheryl L Scudamore; Marianna Tedesco; Ivan del Barco Barrantes; Angel R Nebreda; Paul A Trainor; Andy Greenfield Journal: Dev Cell Date: 2012-10-25 Impact factor: 12.270