Single‐cell <scp>RNA</scp> sequencing reveals new subtypes of lens superficial tissue in humans

Zhu, Mengchao; Hu, Wei; Liu, Lin; Yang, Qingwen; Zhang, Lu; Xu, Jialin; Xu, Yitong; Liu, Jiasheng; Zhang, Meng-Di; Tong, Xiaoyu; Zhu, Kaiyi; Feng, Ke; Feng, Yi; Su, Jianzhong; Huang, Xiu‐Feng; Li, Jin

doi:10.1111/cpr.13477

Cited by 3 publications

(2 citation statements)

References 50 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Our findings are largely consistent with prior studies of adult human and mouse LECs. Previous scRNA-seq of human lens tissue also identified similar LEC subpopulations, 19 as did a study of adult mouse LECs. 99 This study has defined a transcriptomic atlas for the P2 mouse lens epithelium and cataloged the differential gene expression patterns of LEC subpopulations, suggesting a lineage differentiation trajectory for them.…”

Section: Discussionmentioning

confidence: 80%

“… 13 , 14 In order to characterize the different LEC transcriptional states and to probe potential subpopulations that underscore this critical proliferative event, we utilized single-cell RNA sequencing (scRNA-seq) technology. Previous single-cell RNA sequencing studies in the lens have been conducted in zebrafish, 15 , 16 human, 17 – 19 Drosophila , 20 chick, 21 and adult murine lenses. 22 However, the early postnatal mouse lens epithelium has not yet been characterized using this method.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Single-Cell RNA Sequencing Analysis of the Early Postnatal Mouse Lens Epithelium

Giannone,

Sellitto,

Rosati

et al. 2023

Invest. Ophthalmol. Vis. Sci.

View full text Add to dashboard Cite

Purpose The lens epithelium maintains the overall health of the organ. We used single-cell RNA sequencing (scRNA-seq) technology to assess transcriptional heterogeneity between cells in the postnatal day 2 (P2) epithelium and identify distinct epithelial cell subtypes. Analysis of these data was used to better understand lens growth, differentiation, and homeostasis on P2. Methods scRNA-seq on P2 mouse lenses was performed using the 10x Genomics Chromium Single Cell 3′ Kit (v3.1) and short-read Illumina sequencing. Sequence alignment and preprocessing of data were conducted using 10x Genomics Cell Ranger software. Seurat was employed for preprocessing, quality control, dimensionality reduction, and cell clustering, and Monocle was utilized for trajectory analysis to understand the developmental progression of the lens cells. CellChat and GO analyses were used to explore cell–cell communication networks and signaling interactions. Results Lens epithelial cells (LECs) were divided into seven subclusters, classified by specific gene markers. The expression of crystallin, cell-cycle, and metabolic genes was not uniform, indicating distinct functional roles of LECs. Trajectory analysis predicted a bifurcation of differentiating and cycling cells from an Igfbp5+ progenitor pool. We also identified heterogeneity in signaling molecules and pathways, suggesting that cycling and progenitor subclusters have prominent roles in coordinating crosstalk. Conclusions scRNA-seq corroborated many known markers of epithelial differentiation and proliferation while providing further insight into the pathways and genes directing these processes. Interestingly, we demonstrated that the developing epithelium can be divided into distinct subpopulations. These clusters reflect the transcriptionally diverse roles of the epithelium in proliferation, signaling, and maintenance.

show abstract

Section: Discussionmentioning

confidence: 80%

mentioning

confidence: 99%

Single-Cell RNA Sequencing Analysis of the Early Postnatal Mouse Lens Epithelium

Giannone,

Sellitto,

Rosati

et al. 2023

Invest. Ophthalmol. Vis. Sci.

View full text Add to dashboard Cite

show abstract

Integrated single-cell multiomics uncovers foundational regulatory mechanisms of lens development and pathology

Tangeman,

Rebull,

Grajales-Esquivel

et al. 2023

Preprint

View full text Add to dashboard Cite

Ocular lens development entails epithelial to fiber cell differentiation, defects in which cause congenital cataract. We report the first single-cell multiomic atlas of lens development, leveraging snRNA-seq, snATAC-seq, and CUT&RUN-seq to discover novel mechanisms of cell fate determination and cataract-linked regulatory networks. A comprehensive profile of cis- and trans-regulatory interactions, including for the cataract-linked transcription factor MAF, is established across a temporal trajectory of fiber cell differentiation. Further, we divulge a conserved epigenetic paradigm of cellular differentiation, defined by progressive loss of H3K27 methylation writer Polycomb repressive complex 2 (PRC2). PRC2 localizes to heterochromatin domains across master-regulator transcription factor gene bodies, suggesting it safeguards epithelial cell fate. Moreover, we demonstrate that FGF hyper-stimulation in vivo leads to MAF network activation and the emergence of novel lens cell states. Collectively, these data depict a comprehensive portrait of lens fiber cell differentiation, while defining regulatory effectors of cell identity and cataract formation.

show abstract

Integrated single-cell multiomics uncovers foundational regulatory mechanisms of lens development and pathology

Tangeman,

Rebull,

Grajales-Esquivel

et al. 2024

Development

View full text Add to dashboard Cite

Ocular lens development entails epithelial to fiber cell differentiation, defects in which cause congenital cataracts. We report the first single-cell multiomic atlas of lens development, leveraging snRNA-seq, snATAC-seq and CUT&RUN-seq to discover previously unreported mechanisms of cell fate determination and cataract-linked regulatory networks. A comprehensive profile of cis- and trans-regulatory interactions, including for the cataract-linked transcription factor MAF, is established across a temporal trajectory of fiber cell differentiation. Furthermore, we identify an epigenetic paradigm of cellular differentiation, defined by progressive loss of the H3K27 methylation writer Polycomb repressive complex 2 (PRC2). PRC2 localizes to heterochromatin domains across master-regulator transcription factor gene bodies, suggesting it safeguards epithelial cell fate. Moreover, we demonstrate that FGF hyper-stimulation in vivo leads to MAF network activation and the emergence of novel lens cell states. Collectively, these data depict a comprehensive portrait of lens fiber cell differentiation, while defining regulatory effectors of cell identity and cataract formation.

show abstract

Single‐cell RNA sequencing reveals new subtypes of lens superficial tissue in humans

Cited by 3 publications

References 50 publications

Single-Cell RNA Sequencing Analysis of the Early Postnatal Mouse Lens Epithelium

Single-Cell RNA Sequencing Analysis of the Early Postnatal Mouse Lens Epithelium

Integrated single-cell multiomics uncovers foundational regulatory mechanisms of lens development and pathology

Integrated single-cell multiomics uncovers foundational regulatory mechanisms of lens development and pathology

Contact Info

Product

Resources

About