Profiling of chimeric RNAs in human retinal development with retinal organoids

Chimeric RNAs have been found in both cancer and healthy human cells. They have regulatory effects on human stem/progenitor cell differentiation, stemness maintenance and central nervous system (CNS) development. However, their physiological functions in the retinal development remain unknown. Based...

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Bibliographic Details
Published inbioRxiv
Main Authors Wang, Wen, Zhang, Xiao, Zhao, Ning, Ze-Hua Xu, Jin, Kangxin, Zi-Bing Jin
Format Paper
LanguageEnglish
Published Cold Spring Harbor Cold Spring Harbor Laboratory Press 10.11.2022
Subjects
Cell differentiation
Central nervous system
Embryo cells
Embryogenesis
Neural stem cells
Organoids
Progenitor cells
Retina
Retinogenesis
Stem cells
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Summary:Chimeric RNAs have been found in both cancer and healthy human cells. They have regulatory effects on human stem/progenitor cell differentiation, stemness maintenance and central nervous system (CNS) development. However, their physiological functions in the retinal development remain unknown. Based on the human embryonic stem cells (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 causes precocious neuronal differentiation and a marked reduction of neural progenitors in human cerebral organoids. Our study found that CTCL also plays a key role in human retinogenesis, CTCL loss-of-function obstructed RO differentiation but prompted the retinal pigment epithelial (RPE) differentiation. Together, this work provides a landscape of chimeric RNAs and reveals evidence for their crucial roles in human retina development.Competing Interest StatementThe authors have declared no competing interest.
DOI:10.1101/2022.11.10.515982