ArticleFrontiers in cell and developmental biology2021
CRISPR Generated SIX6 and POU4F2 Reporters Allow Identification of Brain and Optic Transcriptional Differences in Human PSC-Derived Organoids.
Article in Frontiers in cell and developmental biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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26 citing papers in PubMed, 34 citations in OpenAlex.
- A human pluripotent stem cell triculture platform to elucidate microglial regulation of retinal ganglion cells in neuroinflammation.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Single-cell analysis reveals cellular heterogeneity and limits of marker-based assessment in retinal ganglion cell-enriched organoid cultures.Molecular medicine (Cambridge, Mass.) · 2026Article
- Blocking apoptosis promotes survival and alters developmental dynamics of human retinal ganglion cells in retinal organoids.Cell reports · 2026Article
- Efficient derivation of stable sheep embryonic stem cells opens a new avenue for agricultural and biomedical application.Journal of advanced research · 2026Article
- SIX3 as a Regulator of Development and Disease.Journal of developmental biology · 2026Review
- Age-Driven Lipid Remodeling Activates Lysosome-Mediated Plasma Membrane Repair.Research square · 2026Article
- DIO3 coordinates photoreceptor development timing and fate stability in human retinal organoids.Genes & development · 2026Article
- Sustained Neurotrophic Factor Co-Treatment Enhances Donor and Host Retinal Ganglion Cell Survival in Mice.Translational vision science & technology · 2025Article
- Article
- Cellular component transfer between photoreceptor cells of the retina.Progress in retinal and eye research · 2025Review
- Optimized Prime Editing of Human Induced Pluripotent Stem Cells to Efficiently Generate Isogenic Models of Mendelian Diseases.International journal of molecular sciences · 2024Article
- A highly reproducible and efficient method for retinal organoid differentiation from human pluripotent stem cells.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Loss of GTF2I promotes neuronal apoptosis and synaptic reduction in human cellular models of neurodevelopment.Cell reports · 2024Article
- Controlling donor and newborn neuron migration and maturation in the eye through microenvironment engineering.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Episodic live imaging of cone photoreceptor maturation in GNAT2-EGFP retinal organoids.Disease models & mechanisms · 2023Article
- Human retinal ganglion cell neurons generated by synchronous BMP inhibition and transcription factor mediated reprogramming.NPJ Regenerative medicine · 2023Article
- Development of a three-dimensional organoid model to explore early retinal phenotypes associated with Alzheimer's disease.Scientific reports · 2023Article
- Unraveling the Drivers of Tumorigenesis in the Context of Evolution: Theoretical Models and Bioinformatics Tools.Journal of molecular evolution · 2023Review
- Single-cell transcriptome analysis of xenotransplanted human retinal organoids defines two migratory cell populations of nonretinal origin.Stem cell reports · 2023Article
- Self-organization, quality control, and preclinical studies of human iPSC-derived retinal sheets for tissue-transplantation therapy.Communications biology · 2023Article
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Authors and funding
16 authors at 5 institutions in 1 country.
Funding
Abstract
Human pluripotent stem cells (PSCs) represent a powerful tool to investigate human eye development and disease. When grown in 3D, they can self-assemble into laminar organized retinas; however, variation in the size, shape and composition of individual organoids exists. Neither the microenvironment nor the timing of critical growth factors driving retinogenesis are fully understood. To explore early retinal development, we developed a SIX6-GFP reporter that enabled the systematic optimization of conditions that promote optic vesicle formation. We demonstrated that early hypoxic growth conditions enhanced SIX6 expression and promoted eye formation. SIX6 expression was further enhanced by sequential inhibition of Wnt and activation of sonic hedgehog signaling. SIX6 + optic vesicles showed RNA expression profiles that were consistent with a retinal identity; however, ventral diencephalic markers were also present. To demonstrate that optic vesicles lead to bona fide "retina-like" structures we generated a SIX6-GFP/POU4F2-tdTomato dual reporter line that labeled the entire developing retina and retinal ganglion cells, respectively. Additional brain regions, including the hypothalamus and midbrain-hindbrain (MBHB) territories were identified by harvesting SIX6 + /POU4F2- and SIX6- organoids, respectively. Using RNAseq to study transcriptional profiles we demonstrated that SIX6-GFP and POU4F2-tdTomato reporters provided a reliable readout for developing human retina, hypothalamus, and midbrain/hindbrain organoids.
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