Evidence map›Paper›PMID 31155355›Full record

ArticleCurrent biology : CB2019

Opposing Effects of Growth and Differentiation Factors in Cell-Fate Specification.

Kun-Che Chang, Catalina Sun, Evan G Cameron, Ankush Madaan, Suqian Wu, Xin Xia, Xiong Zhang, Kevin Tenerelli, Michael Nahmou, Cara M Knasel and 3 more

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

Article in Current biology : CB, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed
2.8field-weighted citation impact, top 10% 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

24 citing papers in PubMed, 29 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 4 institutions in 2 countries.

Kun-Che ChangSpencer Center for Vision Research, Byers Eye Institute, School of Medicine, Stanford University, Palo Alto, CA 94304, USA. Electronic address: kunche@stanford.edu.
Catalina SunSpencer Center for Vision Research, Byers Eye Institute, School of Medicine, Stanford University, Palo Alto, CA 94304, USA.
Evan G CameronSpencer Center for Vision Research, Byers Eye Institute, School of Medicine, Stanford University, Palo Alto, CA 94304, USA.
Ankush MadaanSpencer Center for Vision Research, Byers Eye Institute, School of Medicine, Stanford University, Palo Alto, CA 94304, USA.
Suqian WuSpencer Center for Vision Research, Byers Eye Institute, School of Medicine, Stanford University, Palo Alto, CA 94304, USA; Eye, Ear, Nose, & Throat Hospital, Department of Ophthalmology & Visual Science, Fudan University, 200031 Shanghai, China.
Xin XiaSpencer Center for Vision Research, Byers Eye Institute, School of Medicine, Stanford University, Palo Alto, CA 94304, USA.
Xiong ZhangShiley Eye Center, University of California San Diego, La Jolla, CA 92093, USA.
Kevin TenerelliShiley Eye Center, University of California San Diego, La Jolla, CA 92093, USA.
Michael NahmouSpencer Center for Vision Research, Byers Eye Institute, School of Medicine, Stanford University, Palo Alto, CA 94304, USA.
Cara M KnaselSpencer Center for Vision Research, Byers Eye Institute, School of Medicine, Stanford University, Palo Alto, CA 94304, USA.
Kristina R RussanoSpencer Center for Vision Research, Byers Eye Institute, School of Medicine, Stanford University, Palo Alto, CA 94304, USA; Shiley Eye Center, University of California San Diego, La Jolla, CA 92093, USA; Bascom Palmer Eye Institute, University of Miami, Miami, FL 33136, USA.
Jonathan HertzBascom Palmer Eye Institute, University of Miami, Miami, FL 33136, USA.
Jeffrey L GoldbergSpencer Center for Vision Research, Byers Eye Institute, School of Medicine, Stanford University, Palo Alto, CA 94304, USA; Shiley Eye Center, University of California San Diego, La Jolla, CA 92093, USA; Bascom Palmer Eye Institute, University of Miami, Miami, FL 33136, USA.
Smith-Kettlewell Eye Research Institute · USUniversity of Miami · USUniversity of California San Diego · USFudan University · CN

Funding

Shop Module CoreP30EY008126 · NEI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI Kevin L Schey · 1989 to 2026
$19.6M
Stanford Vision Research CoreP30EY026877 · NEI · STANFORD UNIVERSITY · PI Jeffrey L Goldberg · 2017 to 2026
$8.0M
Retinal Ganglion Cell Replacement in Optic NeuropathiesU24EY029903 · NEI · STANFORD UNIVERSITY · PI CALKINS, DAVID J., GOLDBERG, JEFFREY L · 2018 to 2024
$7.5M
Role of growth and differentiation factors in retinal ganglion cell developmentF32EY029137 · NEI · STANFORD UNIVERSITY · PI CHANG, KUN-CHE · 2018 to 2020
$144k
Retinal Ganglion Cell Differentiation and TransplantationI01BX002950 · VA · VETERANS ADMIN PALO ALTO HEALTH CARE SYS · PI GOLDBERG, JEFFREY L · 2017 to 2020
–
BLRD VA I01 BX002950NEI NIH HHS F32 EY029137NEI NIH HHS P30 EY008126NEI NIH HHS P30 EY026877NEI NIH HHS U24 EY029903
6 · The paper itself

Abstract

Following ocular trauma or in diseases such as glaucoma, irreversible vision loss is due to the death of retinal ganglion cell (RGC) neurons. Although strategies to replace these lost cells include stem cell replacement therapy, few differentiated stem cells turn into RGC-like neurons. Understanding the regulatory mechanisms of RGC differentiation in vivo may improve outcomes of cell transplantation by directing the fate of undifferentiated cells toward mature RGCs. Here, we report a new mechanism by which growth and differentiation factor-15 (GDF-15), a ligand in the transforming growth factor-beta (TGF-β) superfamily, strongly promotes RGC differentiation in the developing retina in vivo in rodent retinal progenitor cells (RPCs) and in human embryonic stem cells (hESCs). This effect is in direct contrast to the closely related ligand GDF-11, which suppresses RGC-fate specification. We find these opposing effects are due in part to GDF-15's ability to specifically suppress Smad-2, but not Smad-1, signaling induced by GDF-11, which can be recapitulated by pharmacologic or genetic blockade of Smad-2 in vivo to increase RGC specification. No other retinal cell types were affected by GDF-11 knockout, but a slight reduction in photoreceptor cells was observed by GDF-15 knockout in the developing retina in vivo. These data define a novel regulatory mechanism of GDFs' opposing effects and their relevance in RGC differentiation and suggest a potential approach for advancing ESC-to-RGC cell-based replacement therapies.

Indexed as

Cell DifferentiationAnimalsGrowth Differentiation Factor 15HumansIntercellular Signaling Peptides and ProteinsMiceMice, Inbred C57BLRetinal Ganglion CellsGDF15 protein, humanGdf15 protein, mouseGrowth Differentiation Factor 15Intercellular Signaling Peptides and ProteinsdifferentiationGDFsretinal developmentretinal ganglion cellstem cellTGF-β signaling

Identifiers

PMID31155355
PMCPMC6581615
OpenAlexW2947075380

What OpenQuestion holds

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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.