RNA Fusion in human retinal development

Abstract
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Abstract

Chimeric RNAs have been found in both cancerous and healthy human cells. They have regulatory effects on human stem/progenitor cell differentiation, stemness maintenance and central nervous system (CNS) development. However, whether they are present in human retinal cells and their physiological functions in the retinal development remain unknown. Based on the human embryonic stem cell (hESC)-derived retinal organoids (ROs) spanning from day 0 to day 120, we present the expression atlas of chimeric RNAs throughout the developing ROs. We confirmed the existence of some common chimeric RNAs and also discovered many novel chimeric RNAs during retinal development. We focused on CTNNBIP1-CLSTN1 (CTCL) whose downregulation caused precocious neuronal differentiation and a marked reduction of neural progenitors in human cerebral organoids. CTCL is universally present in human retinas, retinal organoids and cell lines; however, its loss-of-function biased the progenitor cells toward retinal pigment epithelial (RPE) cell fate at the expense of retinal cells. Together, this work provides a landscape of chimeric RNAs and reveals evidence for their critical role in human retinal development.

Data availability

Sequencing data have been deposited in GSA under accession codes PRJCA020237.All data generated or analysed during this study are included in the manuscript and supporting file; Source Data files have been provided for Figures 4C and 5AB.

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Article and author information

Author details

Wen Wang

Beijing Institute of Ophthalmology, Capital Medical University, Beijing, China

Competing interests
The authors declare that no competing interests exist.
Xiao Zhang

Beijing Institute of Ophthalmology, Beijing, China

Competing interests
The authors declare that no competing interests exist.
Ning Zhao

Beijing Institute of Ophthalmology, Capital Medical University, Beijing, China

Competing interests
The authors declare that no competing interests exist.
Ze-Hua Xu

Beijing Institute of Ophthalmology, Capital Medical University, Beijing, China

Competing interests
The authors declare that no competing interests exist.
Kangxin Jin

Beijing Institute of Ophthalmology, Capital Medical University, Beijing, China

For correspondence
jinkx@mail.ccmu.edu.cn

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0002-0108-6948
Zi-Bing Jin

Beijing Institute of Ophthalmology, Capital Medical University, Beijing, China

For correspondence
jinzibing@foxmail.com

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0003-0515-698X

Funding

National Natural Science Foundation of China (82125007)

Zi-Bing Jin

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Human subjects: One human retinal sample was included in this study, which was derived from a patient's donation. The study was approved by the Ethics Committee of Beijing Tongren Hospital (NO.TRECKY2021-089) and conducted in accordance with the Declaration of Helsinki.

Copyright

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.