Longitudinal single-cell RNA-seq of hESCs-derived retinal organoids

Wang, Shaojun; Poli, Sergio; Liang, Xiaoliang; Peng, Guang-Hua

doi:10.1007/s11427-020-1836-7

Cited by 12 publications

(10 citation statements)

References 61 publications

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“…The outer nuclear layer (ONL) thickness was evaluated throughout the whole retina [ 25 ]. After dewaxing, sections were subjected to antigen retrieval as previously described [ 26 ]. Primary antibodies were purchased from Abcam (anti-rhodopsin, ab221664, 1:600; anti-C3, ab225539, 1:600; mouse monoclonal anti-DNA/RNA Damage [15A3], ab62623, 1:600).…”

Section: Methodsmentioning

confidence: 99%

Complement C3 deficiency alleviates alkylation-induced retinal degeneration in mice

Peng

2022

Eye and Vis

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Background It has been found that the extensive use of anticancer drugs containing DNA-alkylating agents not only target cancer cells but also cause retinal inflammation through toxic intermediates. Complement C3 (C3) is a core component of the complement activation pathway, and dysregulation of the complement pathway is involved in several retinal degenerative diseases. However, whether C3 plays a critical role in alkylation-induced retinal degeneration is unclear. Methods Following treatment with the alkylating agent methyl methane sulfonate (MMS), the C3 mRNA and protein level was measured, DNA damage and photoreceptor cell death were assessed in both wild-type (WT) C57BL/6J and C3 knockout (KO) mice. Results We determined that complement pathway is activated following MMS treatment, and C3 knockout (KO) increased the rate of photoreceptor cell survival and preserved visual function. The mRNA levels of nuclear erythroid-related factor 2 (Nrf2) and related genes were higher after MMS application in C3 KO mice. Conclusion In summary, our study found that C3 KO promotes photoreceptor cell survival and activates the Nrf2 signaling pathway in the context of alkylation-induced retinal degeneration.

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Section: Methodsmentioning

confidence: 99%

Complement C3 deficiency alleviates alkylation-induced retinal degeneration in mice

Peng

2022

Eye and Vis

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“…However, these organoids commonly include multiple lineage cell types (Lancaster and Knoblich, 2014a). For instance, single-cell sequencing results showed that kidney organoids contained non-renal cells, including three neuronal clusters and one muscle cluster, and that retinal organoids contained fibroblast cells and vascular cells (Wu et al, 2018;Wang et al, 2021). If progenitors from a single lineage could be enriched in vitro, the production of unexpected organoid cells could be reduced, and the target organoid would be relatively easy to obtain.…”

Section: Differentiating Into Specific Lineagesmentioning

confidence: 99%

To Better Generate Organoids, What Can We Learn From Teratomas?

Gao

et al. 2021

Front. Cell Dev. Biol.

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The genomic profile of animal models is not completely matched with the genomic profile of humans, and 2D cultures do not represent the cellular heterogeneity and tissue architecture found in tissues of their origin. Derived from 3D culture systems, organoids establish a crucial bridge between 2D cell cultures and in vivo animal models. Organoids have wide and promising applications in developmental research, disease modeling, drug screening, precision therapy, and regenerative medicine. However, current organoids represent only single or partial components of a tissue, which lack blood vessels, native microenvironment, communication with near tissues, and a continuous dorsal-ventral axis within 3D culture systems. Although efforts have been made to solve these problems, unfortunately, there is no ideal method. Teratoma, which has been frequently studied in pathological conditions, was recently discovered as a new in vivo model for developmental studies. In contrast to organoids, teratomas have vascularized 3D structures and regions of complex tissue-like organization. Studies have demonstrated that teratomas can be used to mimic multilineage human development, enrich specific somatic progenitor/stem cells, and even generate brain organoids. These results provide unique opportunities to promote our understanding of the vascularization and maturation of organoids. In this review, we first summarize the basic characteristics, applications, and limitations of both organoids and teratomas and further discuss the possibility that in vivo teratoma systems can be used to promote the vascularization and maturation of organoids within an in vitro 3D culture system.

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“…Wang et al [41] cultured retinal organoids from hESCs (9 different cluster retinal cells from 5 time points were identified), built associations between different cell clusters and focused on the pseudo time molecular regulation of retinal progenitor cells, photoreceptors, retinal pigment epithelium and ganglion cells. Photoreceptor precursors appeared at Day 36 and increased with time, the cone photoreceptor appeared substantially at Day 186, rod photoreceptor cells appeared at Days 126 and 186, RGCs appeared in quantities early at Day 36, and declined from that time.…”

Section: Comparisons Between Human Fetal Retina and Retinal Organoids Developmentmentioning

confidence: 99%

“…It could establish interactions with ligand calmodulin 2(CALM2) in RPCs and RGCs, which in turn could influence the development of photoreceptors. In identification of ganglion cells, a cluster of ganglion cells expressed ipRGCs marker peripherin (PRPH) and gene RAR related orphan receptor B (RORB), which is associated with retinoid metabolism photoreceptor and photoreceptor maturation markers, which may indicate the existence of human ipRGCs [41].…”

Section: Comparisons Between Human Fetal Retina and Retinal Organoids Developmentmentioning

confidence: 99%

Regulatory Mechanisms of Retinal Photoreceptors Development at Single Cell Resolution

Zhao

Peng

2021

IJMS

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Photoreceptors are critical components of the retina and play a role in the first step of the conversion of light to electric signals. With the discovery of the intrinsically photosensitive retinal ganglion cells, which regulate non-image-forming visual processes, our knowledge of the photosensitive cell family in the retina has deepened. Photoreceptor development is regulated by specific genes and proteins and involves a series of molecular processes including DNA transcription, post-transcriptional modification, protein translation, and post-translational modification. Single-cell sequencing is a promising technology for the study of photoreceptor development. This review presents an overview of the types of human photoreceptors, summarizes recent discoveries in the regulatory mechanisms underlying their development at single-cell resolution, and outlines the prospects in this field.

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Longitudinal single-cell RNA-seq of hESCs-derived retinal organoids

Cited by 12 publications

References 61 publications

Complement C3 deficiency alleviates alkylation-induced retinal degeneration in mice

Complement C3 deficiency alleviates alkylation-induced retinal degeneration in mice

To Better Generate Organoids, What Can We Learn From Teratomas?

Regulatory Mechanisms of Retinal Photoreceptors Development at Single Cell Resolution

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