Evidence map›Paper›PMID 31982829›Full record

ArticleEBioMedicine2020

Sphere-induced reprogramming of RPE cells into dual-potential RPE stem-like cells.

Fenghua Chen, Xiao Liu, Yao Chen, John Y Liu, Huayi Lu, Wei Wang, Xiaoqin Lu, Kevin C Dean, Ling Gao, Henry J Kaplan and 3 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in EBioMedicine, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
1.2field-weighted citation impact, top 25% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

13 citing papers in PubMed, 18 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

13 authors at 3 institutions in 2 countries.

Fenghua ChenDepartment of Ophthalmology and Visual Sciences, University of Louisville School of Medicine, 301 E Muhammad Ali Blvd, Louisville, Kentucky 40202, USA; Department of Ophthalmology, Beijing Tongren Hospital, Capital Medical University, Beijing 100005, China.
Xiao LiuDepartment of Ophthalmology and Visual Sciences, University of Louisville School of Medicine, 301 E Muhammad Ali Blvd, Louisville, Kentucky 40202, USA; Department of Ophthalmology, Second Affiliated Hospital of Xiangya Medical School, Central South University, Changsha, China.
Yao ChenDepartment of Ophthalmology and Visual Sciences, University of Louisville School of Medicine, 301 E Muhammad Ali Blvd, Louisville, Kentucky 40202, USA; Department of Ophthalmology, Xiangya Hospital, Central South University, Changsha, China.
John Y LiuDepartment of Ophthalmology and Visual Sciences, University of Louisville School of Medicine, 301 E Muhammad Ali Blvd, Louisville, Kentucky 40202, USA.
Huayi LuDepartment of Ophthalmology and Visual Sciences, University of Louisville School of Medicine, 301 E Muhammad Ali Blvd, Louisville, Kentucky 40202, USA; Second Hospital of Jilin University, Changchun, Jilin Province, China.
Wei WangDepartment of Ophthalmology and Visual Sciences, University of Louisville School of Medicine, 301 E Muhammad Ali Blvd, Louisville, Kentucky 40202, USA.
Xiaoqin LuDepartment of Ophthalmology and Visual Sciences, University of Louisville School of Medicine, 301 E Muhammad Ali Blvd, Louisville, Kentucky 40202, USA.
Kevin C DeanDepartment of Ophthalmology and Visual Sciences, University of Louisville School of Medicine, 301 E Muhammad Ali Blvd, Louisville, Kentucky 40202, USA.
Ling GaoDepartment of Ophthalmology, Second Affiliated Hospital of Xiangya Medical School, Central South University, Changsha, China.
Henry J KaplanDepartment of Ophthalmology and Visual Sciences, University of Louisville School of Medicine, 301 E Muhammad Ali Blvd, Louisville, Kentucky 40202, USA.
Douglas C DeanDepartment of Ophthalmology and Visual Sciences, University of Louisville School of Medicine, 301 E Muhammad Ali Blvd, Louisville, Kentucky 40202, USA; James Graham Brown Cancer Center, University of Louisville School of Medicine, Louisville, Kentucky 40202, USA; Birth Defects Center; University of Louisville School of Medicine, Louisville, Kentucky 40202, USA. Electronic address: dcdean01@louisville.edu.
Xiaoyan PengDepartment of Ophthalmology, Beijing Tongren Hospital, Capital Medical University, Beijing 100005, China. Electronic address: drpengxy@163.com.
Yongqing LiuDepartment of Ophthalmology and Visual Sciences, University of Louisville School of Medicine, 301 E Muhammad Ali Blvd, Louisville, Kentucky 40202, USA; James Graham Brown Cancer Center, University of Louisville School of Medicine, Louisville, Kentucky 40202, USA; Birth Defects Center; University of Louisville School of Medicine, Louisville, Kentucky 40202, USA. Electronic address: y0liu016@louisville.edu.
University of Louisville · USCentral South University · CNBeijing Tongren Hospital · CN

Funding

Molecular Determinants of Developmental DefectsP20GM103453 · NIGMS · UNIVERSITY OF LOUISVILLE · PI GREENE, ROBERT M · 2012 to 2012
$1.7M
NIGMS NIH HHS P20 GM103453
6 · The paper itself

Abstract

backgroundThe retinal pigment epithelium (RPE) has the potential to regenerate the entire neuroretina upon retinal injury in amphibians. In contrast, this regenerative capacity has been lost in mammals. The reprogramming of differentiated somatic cells into induced pluripotent stem cells (iPSCs) by viral transduction of exogenous stem cell factors has triggered a revolution in regenerative medicine. However, the risks of potential mutation(s) caused by random viral vector insertion in host genomes and tumor formation in recipients hamper its clinical application. One alternative is to immortalize adult stem cells with limited potential or to partially reprogram differentiated somatic cells into progenitor-like cells through non-integration protocols.

methodsSphere-induced RPE stem cells (iRPESCs) were generated from adult mouse RPE cells. Their stem cell functionality was studied in a mouse model of retinal degeneration. The molecular mechanism underlying the sphere-induced reprogramming was investigated using microarray and loss-of-function approaches.

findingsWe provide evidence that our sphere-induced reprogramming protocol can immortalize and transform mouse RPE cells into iRPESCs with dual potential to differentiate into cells that express either RPE or photoreceptor markers both in vitro and in vivo. When subretinally transplanted into mice with retinal degeneration, iRPESCs can integrate to the RPE and neuroretina, thereby delaying retinal degeneration in the model animals. Our molecular analyses indicate that the Hippo signaling pathway is important in iRPESC reprogramming.

interpretationThe Hippo factor Yap1 is activated in the nuclei of cells at the borders of spheres. The factors Zeb1 and P300 downstream of the Hippo pathway are shown to bind to the promoters of the stemness genes Oct4, Klf4 and Sox2, thereby likely transactivate them to reprogram RPE cells into iRPESCs. FUND: National Natural Science Foundation of China and the National Institute of Health USA.

Indexed as

Cellular ReprogrammingAnimalsBiomarkersCell DedifferentiationCell DifferentiationCell MovementCells, CulturedCell SeparationCellular SenescenceEpigenesis, GeneticFluorescent Antibody TechniqueKruppel-Like Factor 4MiceMice, TransgenicPhotoreceptor Cells, VertebrateRetinal Pigment EpitheliumBiomarkersKlf4 protein, mouseKruppel-Like Factor 4Cell transplantationRetina degenerationRPE stem cellsSphere-induced reprogramming

Identifiers

PMID31982829
PMCPMC6994567
OpenAlexW3002308702

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.