Biologically Relevant Laminin-511 Moderates the Derivation and Proliferation of Human Lens Epithelial Stem/Progenitor-Like Cells.
Invest Ophthalmol Vis Sci
; 65(10): 12, 2024 Aug 01.
Article
en En
| MEDLINE
| ID: mdl-39106056
ABSTRACT
Purpose:
The role of specific extracellular matrix (ECM) molecules in lens cell development and regeneration is poorly understood, as appropriate cellular models are lacking. Here, a laminin-based lens cell in vitro induction system was developed to study the role of laminin in human lens epithelial stem/progenitor cell (LES/PC) development.Methods:
The human embryonic stem cell-based lens induction system followed a three-stage protocol. The expression profile of laminins during lens induction was screened, and laminin-511 (LN511) was tested as a candidate substitute. LN511 induction system cellular and molecular features, including induction efficiency, transcription factor expression related to different lens development stages, ECM alterations, and Hippo/YAP signaling, were evaluated.Results:
LAMA5, LAMB1, and LAMC1 were highly expressed around the time of LES/PC derivation. We chose LN511 (product of LAMA5, LAMB1, and LAMC1) and found that it considerably enhanced lens cell induction efficiency, compared to that in Matrigel-coated culture, as more and larger lentoid bodies were detected. Notably, LES/PC induction efficiency improved by promoting lens specification-related transcription factor expression and cell proliferation. Transcriptome analysis revealed that compared to those with Matrigel, ECM accumulation and cell adhesion were downregulated in the LN511 system. Hippo/YAP signaling was hypoactive during LES/P-like cell generation, and small molecule inhibitors of YAP/TAZ activity upregulated LES/PC marker expression and promoted the efficiency of LES/P-like cell derivation.Conclusions:
The laminin isoform LN511 is a reliable substitute for the LES/P-like cell induction system, and LN511-YAP acted as efficient modulators of LES/PC derivation; this contributes to knowledge of the role of the ECM in human lens development.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Diferenciación Celular
/
Laminina
/
Proliferación Celular
/
Células Epiteliales
/
Cristalino
Límite:
Humans
Idioma:
En
Revista:
Invest Ophthalmol Vis Sci
Año:
2024
Tipo del documento:
Article
País de afiliación:
China