3D Retinal Organoids Acquire Mature Photoreceptors

Rupendra Shrestha, Yao-Tseng Wen, Dah-Ching Ding, Rong-Kung Tsai

Overview

Despite genetic abnormalities, the hiPSCs showed a positive contribution and efficiently differentiated into 3D retinal organoids. Additionally, the organoids recapitulated retinal neurogenesis and acquired mature photoreceptors, including rod and cone cells.

Summary

This report is the first to show that hiPSCs with abnormal chromosomal content are permissive to the generation of three-dimensional retinal organoids.

Altmetric Statistics

Resources

Aberrant hiPSCs-Derived from Human Keratinocytes Differentiates into 3D Retinal Organoids that Acquire Mature Photoreceptors.

Authors:
Dr. Rupendra Shrestha, MS, PhD
Dr. Rupendra Shrestha, MS, PhD
Albert Einstein College of Medicine
Post-Doctoral Research Fellow
Human Genetics and Stem Cells
Bronx, New York | United States

Cells 2019 01 9;8(1). Epub 2019 Jan 9.

Institute of Medical Sciences, Tzu Chi University, Hualien 970, Taiwan.

Human induced pluripotent stem cell (hiPSC)-derived three-dimensional retinal organoids are a new platform for studying the organoidogenesis. However, recurrent genomic aberration, acquired during generation of hiPSCs, limit its biomedical application and/or aberrant hiPSCs has not been evaluated for generation of differentiated derivatives, such as organoids and retinal pigment epithelium (RPE). In this study, we efficiently differentiated mosaic hiPSCs into retinal organoids containing mature photoreceptors. The feeder-free hiPSCs were generated from the human epidermal keratinocytes that were rapid in process with improved efficiency over several passages and maintained pluripotency. But, hiPSCs were cytogenetically mosaic with normal and abnormal karyotypes, while copy number variation analysis revealed the loss of chromosome 8q. Despite this abnormality, the stepwise differentiation of hiPSCs to form retinal organoids was autonomous and led to neuronal lamination. Furthermore, the use of a Notch inhibitor, DAPT, at an early timepoint from days 29?42 of culture improved the specification of the retinal neuron and the use of retinoic acid at days 70?120 led to the maturation of photoreceptors. hiPSC-derived retinal organoids acquired all subtypes of photoreceptors, such as , and . Additionally, the advanced maturation of photoreceptors was observed, revealing the development of specific sensory cilia and the formation of the outer-segment disc. This report is the first to show that hiPSCs with abnormal chromosomal content are permissive to the generation of three-dimensional retinal organoids.

Download full-text PDF

Source
http://www.mdpi.com/2073-4409/8/1/36
Publisher Site
http://dx.doi.org/10.3390/cells8010036DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6356277PMC
January 2019
43 Reads
4 Citations
5.656 Impact Factor

Publication Analysis

Top Keywords

retinal organoids
24
three-dimensional retinal
8
retinal
8
maturation photoreceptors
8
mature photoreceptors
8
hipscs
7
organoids
7
photoreceptors
5
mosaic normal
4
hipscs cytogenetically
4
additionally advanced
4
maintained pluripotency
4
pluripotency hipscs
4
cytogenetically mosaic
4
passages maintained
4
subtypes photoreceptors
4
copy number
4
acquired subtypes
4
karyotypes copy
4
abnormal karyotypes
4

Similar Publications