Nav: Home

Modeling the human eye in a dish

March 24, 2020

Osaka, Japan - Despite its small size relative to the rest of the body, the eye is one of the most complex organs of the human body and has been difficult to study in a lab. Now, researchers from Osaka University have developed a novel method to model eye development and disease using human induced pluripotent stem cells (hiPSCs). In a new study published in Journal of Biological Chemistry, they showed how tracking the expression of PITX2, a key protein during eye development, in developing hiPSCs enables the isolation of a certain group of cells that play important roles in eye development, biology and disease.

Ever since their discovery over a decade ago, hiPSCs have continued to be used to replicate human biology and disease in a lab without the need for animals. Their streamlined use is accompanied by the possibility of easily genetically altering the cells to study the function of proteins. Although to date several cellular models of multiple organs have been developed using hiPSC, due to its complex and heterogeneous nature, the eye has been more difficult to recreate using these cells.

"Unlike other organs, the eye is more difficult to recreate in the lab due to the presence of heterogeneous cells in the eye," says corresponding author of the study, Ryuhei Hayashi. "The goal of our study was to develop a novel human cellular eye model using hiPSCs that will help improve our understanding of how these different cell types develop to form the eye."

To achieve their goal, the researchers established a reporter cell line by modifying hiPSCs using genome editing technology, such that the cells express the fluorescent protein eGFP whenever they express the protein PITX2. PITX2 is a transcriptional factor protein that plays a key role during embryonic development of several organs, including the eyes. In the eye, PITX2 is specifically expressed in what is called periocular mesenchyme (POM), a collection of cells that give rise to the cornea, as well as muscle cells and connective tissue within the eye. As a result, by using the genetically modified cells, the researchers were able to fluorescently label POM cells.

"We wanted to know whether our new cellular model was able to recreate elements of normal eye development and isolated POM cells for characterization," says lead author of the study Toru Okubo.

The researchers first showed that the modified hiPSCs remained pluripotent after genome editing, so they still maintained the properties of pluripotent stem cells in the same way as unchanged hiPSCs. They then induced the development of POM cells from hiPSCs and showed that they formed so-called self-formed ectodermal autonomous multi-zones (SEAM), which are two-dimensional tissues consisting of different eye cells that form during normal eye development (first reported by Hayashi's group in 2016). Previously, there were no methods to isolate POM cells, but this new generation of gene-edited iPSCs enables the team to isolate POM cells selectively from the SEAM. By isolating the fluorescent POM cells from other, non-fluorescent cells, the researchers were then able to show that POM cells maintained known molecular markers during further cell culture, validating the recreation of eye development using their hiPSC reporter cell line.

"These are striking results that show how human stem cells can be used to study development and disease processes," says Hayashi. "Our model could offer a new opportunity to understand how different aspects of eye development happen."
The article, "Generation and validation of a PITX2-EGFP reporter line of human induced pluripotent stem cells enables isolation of periocular mesenchymal cells," was published in Journal of Biological Chemistry at DOI:

About Osaka University

Osaka University was founded in 1931 as one of the seven imperial universities of Japan and now has expanded to one of Japan's leading comprehensive universities. The University has now embarked on open research revolution from a position as Japan's most innovative university and among the most innovative institutions in the world according to Reuters 2015 Top 100 Innovative Universities and the Nature Index Innovation 2017. The university's ability to innovate from the stage of fundamental research through the creation of useful technology with economic impact stems from its broad disciplinary spectrum.


Osaka University

Related Pluripotent Stem Cells Articles:

More selective elimination of leukemia stem cells and blood stem cells
Hematopoietic stem cells from a healthy donor can help patients suffering from acute leukemia.
Ultrastructure of focal adhesion scaffold unveiled in human pluripotent stem cells
Focal adhesions are known as signalling platforms broadcasting the information of the biochemical and physical qualities of the extracellular matrix into intracellular signalling cascades.
First generation of induced pluripotent stem cells from domestic cats
Researchers have reported for the first time producing feline induced pluripotent stem cells (fiPSCs) from adult cells of domestic cats.
Simple protocol for assessing maturation of HPCs from induced pluripotent stem cells
Researchers have developed a guide to help labs standardize the production of mature hepatic-like cells (HPCs) from stem cells and easily compare gene expression of HPCs to actual human liver tissue.
Researchers characterize 'mutational burden' of human induced pluripotent stem cells
In a new study, published in this week's issue of Cell Reports, researchers at the University of California San Diego School of Medicine scrutinized the whole genome sequences of 18 induced pluripotent stem cell lines derived from skin cells that they had reprogrammed to identify and characterize somatic mutations.
Researchers develop a new method for turning skin cells into pluripotent stem cells
Researchers at the University of Helsinki, Finland, and Karolinska Institutet, Sweden, have for the first time succeeded in converting human skin cells into pluripotent stem cells by activating the cell's own genes.
In mice, stem cells seem to work in fighting obesity! What about stem cells in humans?
This release aims to summarize the available literature in regard to the effect of Mesenchymal Stem Cells transplantation on obesity and related comorbidities from the animal model.
An index measures similarity between cancer cells and pluripotent stem cells
The new methodology measures tumor aggressiveness and the risk of relapse, helping doctors plan treatment, according to Brazilian scientists authors of a paper published in a special issue of the journal Cell.
Induced pluripotent stem cells could serve as cancer vaccine, Stanford researchers say
Induced pluripotent stem cells, or iPS cells, are a keystone of regenerative medicine.
Reproducing higher-order embryonic kidney structures using pluripotent stem cells
In the embryonic kidney, three types of precursor cells interact with each other to form a three-dimensional structure.
More Pluripotent Stem Cells News and Pluripotent Stem Cells Current Events

Trending Science News

Current Coronavirus (COVID-19) News

Top Science Podcasts

We have hand picked the top science podcasts of 2020.
Now Playing: TED Radio Hour

Sound And Silence
Sound surrounds us, from cacophony even to silence. But depending on how we hear, the world can be a different auditory experience for each of us. This hour, TED speakers explore the science of sound. Guests on the show include NPR All Things Considered host Mary Louise Kelly, neuroscientist Jim Hudspeth, writer Rebecca Knill, and sound designer Dallas Taylor.
Now Playing: Science for the People

#576 Science Communication in Creative Places
When you think of science communication, you might think of TED talks or museum talks or video talks, or... people giving lectures. It's a lot of people talking. But there's more to sci comm than that. This week host Bethany Brookshire talks to three people who have looked at science communication in places you might not expect it. We'll speak with Mauna Dasari, a graduate student at Notre Dame, about making mammals into a March Madness match. We'll talk with Sarah Garner, director of the Pathologists Assistant Program at Tulane University School of Medicine, who takes pathology instruction out of...
Now Playing: Radiolab

Kittens Kick The Giggly Blue Robot All Summer
With the recent passing of Ruth Bader Ginsburg, there's been a lot of debate about how much power the Supreme Court should really have. We think of the Supreme Court justices as all-powerful beings, issuing momentous rulings from on high. But they haven't always been so, you know, supreme. On this episode, we go all the way back to the case that, in a lot of ways, started it all.  Support Radiolab by becoming a member today at