Molecular markers for corneal epithelial cells in larval vs. adult Xenopus frogs

Sonam, Surabhi; Srnak, Jennifer A.; Perry, Kimberly J.; Henry, Jonathan J.

doi:10.1016/j.exer.2019.04.010

Cited by 9 publications

(18 citation statements)

References 180 publications

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“…2J). This follows our prior observation of E-Cadherin, as a uniform epithelial cell membrane marker in tadpole corneas (Sonam et al, 2019). Markers associated with Cluster 5 cells (vim.L, vim.S, cd34.L, cd34.S and fn1.S) were molecularly very distinct from the other cell clusters and we classified this cluster as corneal keratocytes (Fig.…”

Section: Single-cell Rna Sequencing Identifies the Major Cell Types Isupporting

confidence: 88%

“…S2C). The presence of closely associated keratocytes underneath the larval corneal epithelium has been previously demonstrated by immunostaining (Sonam et al, 2019). We did not detect significant expression for known marker genes associated with other ocular cell types, such as zp4, pou6f2, pitx2-markers for corneal endothelial cells (Yoshihara et al, 2017;Yoshihara et al, 2015) and cryaa, cryab-markers for lens cells (Brahma and McDevitt, 1974;Henry et al, 2002), indicating absence of these cell types ( Fig.…”

Section: Single-cell Rna Sequencing Identifies the Major Cell Types Isupporting

confidence: 68%

“…S2B). Previously, we found betacatenin as a marker specific for apical epithelial cells in the tadpole cornea (Sonam et al, 2019). However, in the current transcript dataset, the expression of ctnnb.L and ctnnb.S genes was detected in basal cells as well ( Fig.…”

Section: Single-cell Rna Sequencing Identifies the Major Cell Types Icontrasting

confidence: 65%

“…Whereas in the adult frog cornea, long-term BrdU, or EdU label-retaining cells, that likely identify CESCs, become concentrated in the limbal area (Hamilton and Henry, 2016). Furthermore, molecular characterization of corneal epithelia of larval and adult frogs, reveals that putative stem cell markers reported in other vertebrates are expressed at different stages in different epithelial layers of the frog cornea (Sonam et al, 2019). Although these markers label different cellular layers and regions of the corneal epithelium during maturation, none was found to be unique to CESCs or TACs.…”

Section: Introductionmentioning

confidence: 94%

“…1D). In addition, the clusters were examined for biomarkers that we previously characterized in larval Xenopus corneas (Sonam et al, 2019) (Fig. 2).…”

Section: Single-cell Rna Sequencing Identifies the Major Cell Types Imentioning

confidence: 99%

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Single-cell analyses of the corneal epithelium: Unique cell types and gene expression profiles

Sonam

Bangru

Perry

et al. 2020

Preprint

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Corneal Epithelial Stem Cells (CESCs) and their proliferative progeny, the Transit Amplifying Cells (TACs), are responsible for homeostasis and maintaining corneal transparency. Owing to our limited knowledge of cell fates and gene activity within the cornea, the search for unique markers to identify and isolate these cells remains crucial for ocular surface reconstruction. We performed single-cell RNA sequencing of corneal epithelial cells from stage 49-51 Xenopus larvae. We identified five main clusters with distinct molecular signatures, which represent apical, basal and keratocyte cell types as well as two discrete proliferative cell types in the bi-layered epithelium. Our data reveal several novel genes expressed in corneal cells and spatiotemporal changes in gene expression during corneal differentiation. Through gene regulatory network analysis, we identified key developmental gene regulons, which guide these different cell states. Our study offers a detailed atlas of single-cell transcriptomes in the frog corneal epithelium. In future, this work will be useful to elucidate the function of novel genes in corneal homeostasis, wound healing and cornea regeneration, which includes lens regeneration in Xenopus.SUMMARY STATEMENTThis study identifies cell types and transcriptional heterogeneity in the corneal epithelium that regulate its differentiation, and facilitates the search for corneal stem cell markers.

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Section: Single-cell Rna Sequencing Identifies the Major Cell Types Isupporting

confidence: 88%

Section: Single-cell Rna Sequencing Identifies the Major Cell Types Isupporting

confidence: 68%

Section: Single-cell Rna Sequencing Identifies the Major Cell Types Icontrasting

confidence: 65%

Section: Introductionmentioning

confidence: 94%

“…1D). In addition, the clusters were examined for biomarkers that we previously characterized in larval Xenopus corneas (Sonam et al, 2019) (Fig. 2).…”

Section: Single-cell Rna Sequencing Identifies the Major Cell Types Imentioning

confidence: 99%

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Single-cell analyses of the corneal epithelium: Unique cell types and gene expression profiles

Sonam

Bangru

Perry

et al. 2020

Preprint

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Understanding cornea epithelial stem cells and stem cell deficiency: Lessons learned using vertebrate model systems

Adil

Henry

2021

Genesis

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Summary Animal models have contributed greatly to our understanding of human diseases. Here, we focus on cornea epithelial stem cell (CESC) deficiency (commonly called limbal stem cell deficiency, LSCD). Corneal development, homeostasis and wound healing are supported by specific stem cells, that include the CESCs. Damage to or loss of these cells results in blindness and other debilitating ocular conditions. Here we describe the contributions from several vertebrate models toward understanding CESCs and LSCD treatments. These include both mammalian models, as well as two aquatic models, Zebrafish and the amphibian, Xenopus. Pioneering developments have been made using stem cell transplants to restore normal vision in patients with LSCD, but questions still remain about the basic biology of CESCs, including their precise cell lineages and behavior in the cornea. We describe various cell lineage tracing studies to follow their patterns of division, and the fates of their progeny during development, homeostasis, and wound healing. In addition, we present some preliminary results using the Xenopus model system. Ultimately, a more thorough understanding of these cornea cells will advance our knowledge of stem cell biology and lead to better cornea disease therapeutics.

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Understanding cornea homeostasis and wound healing using a novel model of stem cell deficiency in Xenopus

Adil

Simons

Sonam

et al. 2019

Experimental Eye Research

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Molecular markers for corneal epithelial cells in larval vs. adult Xenopus frogs

Cited by 9 publications

References 180 publications

Single-cell analyses of the corneal epithelium: Unique cell types and gene expression profiles

Single-cell analyses of the corneal epithelium: Unique cell types and gene expression profiles

Understanding cornea epithelial stem cells and stem cell deficiency: Lessons learned using vertebrate model systems

Understanding cornea homeostasis and wound healing using a novel model of stem cell deficiency in Xenopus

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