June 2023
Volume 64, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2023
Single-nuclei Multiomics Analysis of Human Organoids and Fetal Retina Reveals Developmental Transcriptional and Epigenetic Differences
Author Affiliations & Notes
  • Salma Ferdous
    Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, United States
  • Zhen Zuo
    Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, United States
  • Yang Zhang
    Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, United States
  • Xinye Qian
    Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, United States
  • Yumei Li
    Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, United States
  • Xuesen Cheng
    Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, United States
  • Jin Li
    Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, United States
  • Alice Tian
    Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, United States
  • Joseph Quinlan
    Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, United States
  • Yourong Bao
    Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, United States
  • Antonio Jacobo Lopez
    University of California Davis Medical Center Department of Orthopaedic Surgery, Sacramento, California, United States
  • Ala Moshiri
    University of California Davis Medical Center Department of Orthopaedic Surgery, Sacramento, California, United States
  • Rui Chen
    Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, United States
  • Footnotes
    Commercial Relationships   Salma Ferdous None; Zhen Zuo None; Yang Zhang None; Xinye Qian None; Yumei Li None; Xuesen Cheng None; Jin Li None; Alice Tian None; Joseph Quinlan None; Yourong Bao None; Antonio Lopez None; Ala Moshiri None; Rui Chen None
  • Footnotes
    Support  NLM, FFB TA-RM-0522-0825, CZF2019-002425
Investigative Ophthalmology & Visual Science June 2023, Vol.64, 1867. doi:
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      Salma Ferdous, Zhen Zuo, Yang Zhang, Xinye Qian, Yumei Li, Xuesen Cheng, Jin Li, Alice Tian, Joseph Quinlan, Yourong Bao, Antonio Jacobo Lopez, Ala Moshiri, Rui Chen; Single-nuclei Multiomics Analysis of Human Organoids and Fetal Retina Reveals Developmental Transcriptional and Epigenetic Differences. Invest. Ophthalmol. Vis. Sci. 2023;64(8):1867.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : Retinal organoid represents a potentially excellent model system to study developmental processes in vivo. We aim to perform a systematic comparison of gene expression profiles, transcriptional trajectories, and chromatin accessibility between retinal organoids and the developing human retina.

Methods : Retinal organoid samples from 5- and 45-weeks and human fetal retinal samples between 10- and 23-weeks gestational age were collected and subjected to single nuclei multiome profiling using the 10X Genomics platform to generate transcriptomic and open chromatin data from the same nuclei. After co-embedding, RNA velocity and pseudotime trajectory were calculated with Monocle and MultiVelo. ArchR was used to identify changes in chromatin openness.

Results : In total, single nuclei multiome profiling of 350,000 nuclei has been generated from 10 retinal organoid samples and 24 fetal retinal samples. All major cell classes and more than 30 cell types have been identified in the organoid. Furthermore, based on pseudotime analysis, the organoid trajectory was well matched to the trajectory inferred from fetal samples. By analyzing cells within the same cell type between organoid and fetal samples, transcriptional and chromatin openness similarities/differences were identified.

Conclusions : Our study has produced a multiomics atlas of both the human fetal retina and retinal organoid across different developmental stages. Through integrative and comparative analysis of these datasets, we identified both shared and unique regulatory mechanisms that control the developmental process. These mechanisms were revealed through the comparison between the transcriptome and open chromatin profile in the organoid and fetal samples and involve complex and dynamic interactions between the genome and epigenome. Overall, our study broadens our understanding of the extend to which retinal organoids mimic normal human retinal development.

This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.

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