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

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Abstract

Human retina development involves multiple well-studied signaling pathways that promote the genesis of a wide arrange of different cell types in a complex architectural structure. Human embryonic stem cells (hESCs)-derived retinal organoids could recapitulate the human retinal development. We performed single-cell RNA-seq of retinal organoids from 5 time points (D36, D66, D96, D126, D186) and identified 9 distinct populations of cells. In addition, we analyzed the molecular characteristics of each main population and followed them from genesis to maturity by pseudotime analysis and characterized the cell-cell interactions between different cell types. Interestingly, we identified insulin receptor (INSR) as a specifically expressed receptor involved in the genesis of photoreceptors, and pleiothropin (PTN)-protein tyrosine phosphatase receptor type Z1 (PTPRZ1) as a mediator of a previously unknown interaction between Müller and retinal progenitor cells. Taken together, these findings provide a rich transcriptome-based lineage map for studying human retinal development and modeling developmental disorders in retinal organoids.

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Acknowledgements

This work was supported by the National Key Research and Development Program (2018YFA0107303), the National Natural Science Foundation of China (82070990), Initiation Fund of Distinguished Professor, Zhengzhou University (32310180), China Postdoctoral Research Fund (2017M613396).

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  1. Sergio Poli

    Present address: Current address: Division of Internal Medicine, Mount Sinai Medical Center, Miami, Florida, 33140, USA

Authors and Affiliations

  1. Laboratory of Visual Cell Differentiation and Regulation, Basic Medical College, Zhengzhou University, Zhengzhou, 450001, China

    Guang-Hua Peng

  2. Department of Ophthalmology, First medical center of Chinese PLA General Hospital, Beijing, 100853, China

    Shaojun Wang

  3. Department of Ophthalmology, Fifth medical center of Chinese PLA General Hospital, Beijing, 100071, China

    Shaojun Wang

  4. Division of Pulmonary and Critical Care Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, 02115, USA

    Sergio Poli & Xiaoliang Liang

  5. Department of Pathophysiology, Basic Medical College, Zhengzhou University, Zhengzhou, 450001, China

    Guang-Hua Peng

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Wang, S., Poli, S., Liang, X. et al. Longitudinal single-cell RNA-seq of hESCs-derived retinal organoids. Sci. China Life Sci. 64, 1661–1676 (2021). https://doi.org/10.1007/s11427-020-1836-7

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