Exploring the Cocktail Factor Approach to Generate Salivary Gland Progenitors through Co-Culture Techniques
10.1007/s13770-024-00632-6
- Author:
Yifei ZHANG
1
;
Shuang YAN
;
Zi MEI
;
He ZHANG
;
Chong DING
;
Siqi ZHANG
;
Shicheng WEI
Author Information
1. Central Laboratory and Department of Oral and Maxillofacial Surgery School and Hospital of Stomatology, Peking University, Beijing 100081, China
- Publication Type:ORIGINAL ARTICLE
- From:
Tissue Engineering and Regenerative Medicine
2024;21(5):749-759
- CountryRepublic of Korea
- Language:EN
-
Abstract:
BACKGROUND:The derivation of salivary gland (SG) progenitors from pluripotent stem cells (PSCs) presents significant potential for developmental biology and regenerative medicine. However, the existing protocols for inducing SG include limited factors, making it challenging to mimic the in vivo microenvironment of embryonic SGs.
METHODS:We reported a cocktail factor approach to promote the differentiation of mouse embryonic stem cell (mESC)-derived oral epithelium (OE) into SG progenitors through a three-dimensional co-culture method. Upon confirming that the embryonic SG can promote the differentiation of mESC-derived OE, we performed RNA sequence analysis to identify factors involved in the differentiation of SG progenitors.
RESULTS:Our findings highlight several efficient pathways related to SG development, with frequent appearances of four factors: IFN-c, TGF-b2, EGF, and IGF-1. The combined treatment using these cocktail factors increased the expression of key SG progenitor markers, including Sox9, Sox10, Krt5, and Krt14. However, absence of any one of these cocktail factors did not facilitate differentiation. Notably, aggregates treated with the cocktail factor formed SG epitheliallike structures and pre-bud-like structures on the surface.
CONCLUSION:In conclusion, this study offers a novel approach to developing a differentiation protocol that closely mimics the in vivo microenvironment of embryonic SGs. This provides a foundation for generating PSC-derived organoids with near-physiological cell behaviors and structures.
