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Tet2和Tet3在视网膜发育过程中调节细胞命运特化和分化事件。

tet2 and tet3 regulate cell fate specification and differentiation events during retinal development.

作者信息

Heilman Shea A, Schriever Hannah C, Kostka Dennis, Koenig Kristen M, Gross Jeffrey M

机构信息

Department of Ophthalmology, The Louis J. Fox Center for Vision Restoration, The McGowan Institute for Regenerative Medicine, The University of Pittsburgh School of Medicine, Pittsburgh, PA, United States of America.

Department of Computational Biology, The University of Pittsburgh School of Medicine, Pittsburgh, PA, United States of America.

出版信息

bioRxiv. 2024 Dec 10:2024.12.06.627071. doi: 10.1101/2024.12.06.627071.

DOI:10.1101/2024.12.06.627071
PMID:39713311
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11661121/
Abstract

Tet enzymes are epigenetic modifiers that impact gene expression via 5mC to 5hmC oxidation. Previous work demonstrated the requirement for Tet and 5hmC during zebrafish retinogenesis. mutants possessed defects in the formation of differentiated retinal neurons, but the mechanisms underlying these defects are unknown. Here, we leveraged scRNAseq technologies to better understand cell type-specific deficits and molecular signatures underlying the retinal phenotype. Our results identified defects in the retinae that included delayed specification of several retinal cell types, reduced maturity across late-stage cones, expansions of immature subpopulations of horizontal and bipolar cells, and altered biases of bipolar cell subtype fates at late differentiation stages. Together, these data highlight the critical role that tet2 and tet3 play as regulators of cell fate specification and terminal differentiation events during retinal development.

摘要

Tet酶是通过5-甲基胞嘧啶(5mC)氧化为5-羟甲基胞嘧啶(5hmC)来影响基因表达的表观遗传修饰因子。先前的研究表明斑马鱼视网膜发生过程中需要Tet和5hmC。tet突变体在分化的视网膜神经元形成过程中存在缺陷,但这些缺陷背后的机制尚不清楚。在这里,我们利用单细胞RNA测序(scRNAseq)技术来更好地了解视网膜表型背后的细胞类型特异性缺陷和分子特征。我们的结果确定了视网膜中的缺陷,包括几种视网膜细胞类型的特化延迟、晚期视锥细胞成熟度降低、水平细胞和双极细胞未成熟亚群的扩张,以及双极细胞亚型命运在晚期分化阶段的偏差改变。总之,这些数据突出了tet2和tet3作为视网膜发育过程中细胞命运特化和终末分化事件调节因子所起的关键作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f1a/11661121/83ddd1ae64bb/nihpp-2024.12.06.627071v1-f0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f1a/11661121/1ed6f6bcda06/nihpp-2024.12.06.627071v1-f0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f1a/11661121/dbb84159bb3a/nihpp-2024.12.06.627071v1-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f1a/11661121/f52112ee208f/nihpp-2024.12.06.627071v1-f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f1a/11661121/bdaaacec6525/nihpp-2024.12.06.627071v1-f0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f1a/11661121/83ddd1ae64bb/nihpp-2024.12.06.627071v1-f0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f1a/11661121/1ed6f6bcda06/nihpp-2024.12.06.627071v1-f0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f1a/11661121/dbb84159bb3a/nihpp-2024.12.06.627071v1-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f1a/11661121/f52112ee208f/nihpp-2024.12.06.627071v1-f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f1a/11661121/bdaaacec6525/nihpp-2024.12.06.627071v1-f0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f1a/11661121/83ddd1ae64bb/nihpp-2024.12.06.627071v1-f0005.jpg

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本文引用的文献

1
Isolation and Preparation of Embryonic Zebrafish Retinal Cells for Single-Cell RNA Sequencing.胚胎斑马鱼视网膜细胞的分离和制备用于单细胞 RNA 测序。
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Ancient origin of the rod bipolar cell pathway in the vertebrate retina.脊椎动物视网膜中杆双极细胞通路的远古起源。
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Single-cell analysis of shared signatures and transcriptional diversity during zebrafish development.
单细胞分析斑马鱼发育过程中的共享特征和转录多样性。
Dev Cell. 2023 Dec 18;58(24):3028-3047.e12. doi: 10.1016/j.devcel.2023.11.001. Epub 2023 Nov 22.
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Epigenetic regulation in the commitment of progenitor cells during retinal development and regeneration.视网膜发育和再生过程中祖细胞定向分化中的表观遗传调控。
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A temporal single cell transcriptome atlas of zebrafish anterior segment development.斑马鱼眼前段发育的时间单细胞转录组图谱。
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Key transcription factors influence the epigenetic landscape to regulate retinal cell differentiation.关键转录因子影响表观遗传景观,以调节视网膜细胞分化。
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Mammalian DNA methylome dynamics: mechanisms, functions and new frontiers.哺乳动物 DNA 甲基组动态:机制、功能与新前沿。
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Grk7 but not Grk1 undergoes cAMP-dependent phosphorylation in zebrafish cone photoreceptors and mediates cone photoresponse recovery to elevated cAMP.Grk7 而非 Grk1 在斑马鱼视锥光感受器中经历 cAMP 依赖性磷酸化,并介导对升高的 cAMP 的锥光感受器光反应恢复。
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Retinal TRP channels: Cell-type-specific regulators of retinal homeostasis and multimodal integration.视网膜 TRP 通道:视网膜内稳态和多模态整合的细胞类型特异性调节剂。
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The Potential Role of Epigenetic Mechanisms in the Development of Retinitis Pigmentosa and Related Photoreceptor Dystrophies.表观遗传机制在视网膜色素变性及相关光感受器营养不良发生发展中的潜在作用
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