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Extracellular matrix components expression in human pluripotent stem cell-derived retinal organoids recapitulates retinogenesis in vivo and reveals an important role for IMPG1 and CD44 in the development of photoreceptors and interphotoreceptor matrix

Lookup NU author(s): Majed Felemban, Dr Nicola Hunt, Dr Dean Hallam, Dr Darin Zerti, Dr Roman Bauer, Dr Yuchun Ding, Dr Joseph Collin, David Steel, Professor Natalio Krasnogor, Professor Susan Lindsay, Dr Carla Mellough, Professor Majlinda Lako

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This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


Abstract

The extracellular matrix (ECM) plays an important role in numerous processes including cellular proliferation, differentiation, migration, maturation, adhesion guidance and axonal growth. To date, there has been no detailed analysis of the ECM distribution during retinal ontogenesis in humans and the functional importance of many ECM components is poorly understood. In this study, the expression of key ECM components in adult mouse and monkey retina, developing and adult human retina and retinal organoids derived from human pluripotent stem cells was studied. Our data indicate that basement membrane ECMs (Fibronectin and Collagen IV) were expressed in Bruch’s membrane and the inner limiting membrane of the developing human retina, whilst the hyalectins (Versican and Brevican), cluster of differentiation 44 (CD44), photoreceptor-specific ECMs Interphotoreceptor Matrix Proteoglycan 1 (IMPG1) and Interphotoreceptor Matrix Proteoglycan 2 (IMPG2) were detected in the developing interphotoreceptor matrix (IPM). The expression of IMPG1, Versican and Brevican in the developing IPM was conserved between human developing retina and human pluripotent stem cell-derived retinal organoids. Blocking the action of CD44 and IMPG1 in pluripotent stem cell derived retinal organoids affected the development of photoreceptors, their inner/outer segments and connecting cilia and disrupted IPM formation, with IMPG1 having an earlier and more significant impact. Together, our data suggest an important role for IMPG1 and CD44 in the development of photoreceptors and IPM formation during human retinogenesis.


Publication metadata

Author(s): Felemban M, Dorgau B, Hunt NC, Hallam D, Zerti D, Bauer R, Ding Y, Collin J, Steel DH, Krasnogor N, Al-Aama J, Lindsay S, Mellough C, Lako M

Publication type: Article

Publication status: Published

Journal: Acta Biomaterialia

Year: 2018

Volume: 74

Pages: 207-221

Print publication date: 01/07/2018

Online publication date: 17/05/2018

Acceptance date: 15/05/2018

Date deposited: 15/05/2018

ISSN (print): 1742-7061

ISSN (electronic): 1878-7568

Publisher: Elsevier BV

URL: https://doi.org/10.1016/j.actbio.2018.05.023

DOI: 10.1016/j.actbio.2018.05.023


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