Evidence map›Paper›PMID 42401922›Full record

ArticleStem cell research & therapy2026

Identification and enrichment of human retinal organoid-derived red/green cone-competent precursors with enhanced axon dynamics.

Praveen J Susaimanickam, Elizabeth Capowski, Mai N Xiong, Kimberly L Edwards, Yashdeep Phanse, Madalynn J Welch, Austin Pier, Steven J Mayerl, Maria A Fernandez Zepeda, Kyle D Peterson and 4 more

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Article in Stem cell research & therapy, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

What it found

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2 · The registry

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3 · Its place in the literature

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4 · The record

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5 · Who and what money

Authors and funding

14 authors.

Praveen J SusaimanickamWaisman Center, University of Wisconsin-Madison, Madison, USA.
Elizabeth CapowskiWaisman Center, University of Wisconsin-Madison, Madison, USA.
Mai N XiongWaisman Center, University of Wisconsin-Madison, Madison, USA.
Kimberly L EdwardsWaisman Center, University of Wisconsin-Madison, Madison, USA.
Yashdeep PhanseWaisman Center, University of Wisconsin-Madison, Madison, USA.
Madalynn J WelchDepartment of Neuroscience, University of Wisconsin-Madison, Madison, USA.
Austin PierMcPherson Eye Research Institute, University of Wisconsin-Madison, Madison, USA.
Steven J MayerlWaisman Center, University of Wisconsin-Madison, Madison, USA.
Maria A Fernandez ZepedaWaisman Center, University of Wisconsin-Madison, Madison, USA.
Kyle D PetersonDepartment of Ophthalmology and Visual Sciences, University of Wisconsin-Madison, Madison, USA.
M Joseph PhillipsWaisman Center, University of Wisconsin-Madison, Madison, USA.
Divya SinhaWaisman Center, University of Wisconsin-Madison, Madison, USA.
Timothy M GomezMcPherson Eye Research Institute, University of Wisconsin-Madison, Madison, USA.
David M GammWaisman Center, University of Wisconsin-Madison, Madison, USA. dgamm@wisc.edu.

Funding

UW COMPREHENSIVE CANCER CENTER SUPPORTP30CA014520 · NCI · UNIVERSITY OF WISCONSIN-MADISON · PI Justine Yang Bruce · 1985 to 2026
$142.6M
Waisman Center Intellectual and Developmental Disabilities Research CenterP50HD105353 · NICHD · UNIVERSITY OF WISCONSIN-MADISON · PI Qiang Chang · 2021 to 2026
$8.5M
Mechanisms of mTOR-independent axon growth and guidance defects in TSC2 mutant human neuronsR01NS113314 · NINDS · UNIVERSITY OF WISCONSIN-MADISON · PI GOMEZ, TIMOTHY M · 2020 to 2024
$1.8M
McPherson Eye Research Institute Kenzi Valentyn Vision Research AwardNCI NIH HHS P30 CA014520NICHD NIH HHS P50 HD105353NINDS NIH HHS R01 NS113314U.S. Department of Defense W81XWH2010655
6 · The paper itself

Abstract

backgroundCell replacement therapies aimed at restoring foveal vision require a robust source of red/green (long/medium wavelength, or L/M) cone photoreceptors with intrinsic properties conducive to functional integration into host retina. Recent evidence has shown that cones present within mature human retinal organoids (ROs) can generate light responses comparable to macaque foveal cones. However, only cone precursors from early developing ROs possess a capacity for cell-autonomous axonogenesis. Therefore, we sought to identify and enrich for a population of early L/M cone-competent precursors with intrinsically superior axon dynamics that would provide an ideal donor cell source for future foveal reconstruction efforts.

methodsWe developed a dual L/M cone/rod reporter (L/M-CRR) line to unequivocally identify early L/M cone-competent precursors from human ROs. To do so, we used CRISPR/Cas9 to link a tdTomato transgene to the endogenous THRB2 promoter in the WA09 NRL

resultsTHRB2-driven tdTomato fluorescence faithfully demarcated L/M cone-competent precursors throughout RO development, although fluorescence declined in later ROs as L/M cones matured. Transcriptomic profiling revealed that day 50 sorted tdTomato

conclusionsThe L/M-CRR line enables definitive identification and transcriptomic characterization of L/M cone-competent precursors throughout early to mid-stage RO development. Our investigation also revealed that CD166/ALCAM can be used to independently identify and enrich for a subset of early L/M cone-competent precursors that selectively display axon dynamicity conducive for retinal circuit integration. Our studies provide the first insights into early human L/M cone development and establish a method to isolate L/M cone-competent precursors with enhanced axon dynamics, which constitutes a compelling cell population for treating central vision loss caused by photoreceptor degeneration.

Indexed as

AxonsOrganoidsRetinaRetinal Cone Photoreceptor CellsAnimalsCell DifferentiationHumansCD166/ALCAMCell replacement therapyCone-rod reporter lineL/M conesMacular diseasesPhotoreceptor axon extensionPluripotent stem cellsRetinal organoids

Identifiers

PMID42401922
PMCPMC13613627

What Socratic holds

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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 Socratic graph.