Transcriptome Analysis of Newt Lens Regeneration Reveals Distinct Gradients in Gene Expression Patterns

Sousounis, Konstantinos; Looso, Mario; Maki, Nobuyasu; Ivester, Clifford J.; Braun, Thomas; Tsonis, Panagiotis A.

doi:10.1371/journal.pone.0061445

Cited by 41 publications

(39 citation statements)

References 148 publications

(144 reference statements)

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“…The genes that were expressed differently between young and old axolotl larvae reveal age‐related differences in transcription, metabolism, cell proliferation, differentiation, and immune response. We report further insights by comparing genes identified between young and old axolotl iris to genes that were identified recently from dorsal and ventral irises of newts (Sousounis et al ).…”

Section: Introductionmentioning

confidence: 68%

Plasticity for axolotl lens regeneration is associated with age‐related changes in gene expression

et al. 2014

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Mexican axolotls lose potential for lens regeneration 2 weeks after hatching. We used microarrays to identify differently expressed genes before and after this critical time, using RNA isolated from iris. Over 3700 genes were identified as differentially expressed in response to lentectomy between young (7 days post‐hatching) and old (3 months post‐hatching) axolotl larvae. Strikingly, many of the genes were only expressed in the early or late iris. Genes that were highly expressed in young iris significantly enriched electron transport chain, transcription, metabolism, and cell cycle gene ontologies, all of which are associated with lens regeneration. In contrast, genes associated with cellular differentiation and tissue maturation were uniquely expressed in old iris. Many of these expression differences strongly suggest that young and old iris samples were collected before and after the spleen became developmentally competent to produce and secrete cells with humoral and innate immunity functions. Our study establishes the axolotl as a powerful model to investigate age‐related cellular differentiation and immune system ontogeny within the context of tissue regeneration.

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Section: Introductionmentioning

confidence: 68%

Plasticity for axolotl lens regeneration is associated with age‐related changes in gene expression

et al. 2014

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“…These efforts have generated large expression datasets for normal and defective lens development (Agrawal et al, 2015; Anand et al, 2015; Audette et al, 2016; Chauhan et al, 2002a, 2002b; Chauss et al, 2014; De Maria and Bassnett, 2015; Greiling et al, 2009; Hawse et al, 2005, 2004, 2003; Hoang et al, 2014; Ivanov et al, 2005; Khan et al, 2016, 2015; Kumar et al, 2015; Lachke et al, 2012b, 2011; Manthey et al, 2014a; Sousounis et al, 2015, 2013; Sousounis and Tsonis, 2012; Wistow et al, 2002; Wolf et al, 2013b; Wride et al, 2003; Xiao et al, 2006). Although highly informative, early microarray studies used platforms representing only a subset of genes ( n =9,700) in the mouse genome (Chauhan et al, 2002a, 2002b).…”

Section: Genome-level Expression Profiling Of Lens Developmentmentioning

confidence: 99%

“…Besides these efforts, high-throughput expression profiling was performed on lenses in other animal models (Chauss et al, 2014; Sousounis et al, 2015, 2013). However, the strength of high-throughput expression profiling – providing genome-wide data – perhaps poses its greatest challenge, because these approaches identify thousands of transcripts that are scored as “expressed”.…”

Section: Future Of Lens Research: Toward Lens Systems Biologymentioning

confidence: 99%

“…1), several of which are discussed in detail in later sections, and for which the following studies are representative (Chauhan et al, 2002b; Hammond et al, 2001; Hawse et al, 2003; Lachke et al, 2012b; Lampi et al, 2002; Sousounis et al, 2013; Tsentalovich et al, 2015; Ueda et al, 2002; Yanshole et al, 2014). These approaches have generated immense quantities of data.…”

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confidence: 99%

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Systems biology of lens development: A paradigm for disease gene discovery in the eye

Anand

Lachke

2017

Experimental Eye Research

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Over the past several decades, the biology of the developing lens has been investigated using molecular genetics-based approaches in various vertebrate model systems. These efforts, involving target gene knockouts or knockdowns, have led to major advances in our understanding of lens morphogenesis and the pathological basis of cataracts, as well as of other lens related eye defects. In particular, we now have a functional understanding of regulators such as Pax6, Six3, Sox2, Oct1 (Pou2f1), Meis1, Pnox1, Zeb2 (Sip1), Mab21l1, Foxe3, Tfap2a (Ap2-alpha), Pitx3, Sox11, Prox1, Sox1, c-Maf, Mafg, Mafk, Hsf4, Fgfrs, Bmp7, and Tdrd7 in this tissue. However, whether these individual regulators interact or their targets overlap, and the significance of such interactions during lens morphogenesis, is not well defined. The arrival of high-throughput approaches for gene expression profiling (microarrays, RNA-sequencing (RNA-seq), etc.), which can be coupled with chromatin immunoprecipitation (ChIP) or RNA immunoprecipitation (RIP) assays, along with improved computational resources and publically available datasets (e.g. those containing comprehensive protein-protein, protein-DNA information), presents new opportunities to advance our understanding of the lens tissue on a global systems level. Such systems-level knowledge will lead to the derivation of the underlying lens gene regulatory network (GRN), defined as a circuit map of the regulator-target interactions functional in lens development, which can be applied to expedite cataract gene discovery. In this review, we cover the various systems-level approaches such as microarrays, RNA-seq, and ChIP that are already being applied to lens studies and discuss strategies for assembling and interpreting these vast amounts of high-throughput information for effective dispersion to the scientific community. In particular, we discuss strategies for effective interpretation of this new information in the context of the rich knowledge obtained through the application of traditional single-gene focused experiments on the lens. Finally, we discuss our vision for integrating these diverse high-throughput datasets in a single web-based user-friendly tool iSyTE (integrated Systems Tool for Eye gene discovery) – a resource that is already proving effective in the identification and characterization of genes linked to lens development and cataract. We anticipate that application of a similar approach to other ocular tissues such as the retina and the cornea, and even other organ systems, will significantly impact disease gene discovery.

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“…Whereas a typical NGS approach in eukaryote model organisms (and also niche models, e.g. [47]) reports a couple of ten thousands of transcripts in a quantitative manner, a proteomics approach allows the identification and quantification of a couple of thousand proteins in well-established model organisms. For instance, a recent study with zebrafish revealed 2,100 proteins [48], a new protocol to identify human proteins out of paraffin-embedded samples even allowed the identification of 10,000 proteins [49] (details see Box 1).…”

Section: Investigation Of Unknown Proteinsmentioning

confidence: 99%

Opening the genetic toolbox of niche model organisms with high throughput techniques: Novel proteins in regeneration as a case study

Looso

2014

BioEssays

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Understanding in vivo regeneration of complex structures offers a fascinating perspective for translation into medical applications. Unfortunately, mammals in general lack large-scale regenerative capacity, whereas planarians, newts or Hydra can regenerate complete body parts. Such organisms are, however, poorly annotated because of the lack of sequence information. This leads to limited access for molecular biological investigations. In the last decade, high throughput technologies and new methods enabling the effective generation of transgenic animals have rapidly evolved. These developments have allowed the extensive use of niche model organisms as part of a trend towards the accessibility of a greater panel of model species for scientific research. The case study that follows provides an insight into the impact of high throughput techniques on the landscape of models of regeneration. The cases presented here give evidence of alternative stem cell maintenance pathways, the identification of new protein families and new stem cell markers.

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Transcriptome Analysis of Newt Lens Regeneration Reveals Distinct Gradients in Gene Expression Patterns

Cited by 41 publications

References 148 publications

Plasticity for axolotl lens regeneration is associated with age‐related changes in gene expression

Plasticity for axolotl lens regeneration is associated with age‐related changes in gene expression

Systems biology of lens development: A paradigm for disease gene discovery in the eye

Opening the genetic toolbox of niche model organisms with high throughput techniques: Novel proteins in regeneration as a case study

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