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  1. Article ; Online: In Vivo and Ex Vivo View of Newt Lens Regeneration.

    Tsissios, Georgios / Sallese, Anthony / Chen, Weihao / Miller, Alyssa / Wang, Hui / Del Rio-Tsonis, Katia

    Methods in molecular biology (Clifton, N.J.)

    2022  Volume 2562, Page(s) 197–208

    Abstract: Lens regeneration in the adult newt illustrates a unique example of naturally occurring cell transdifferentiation. During this process, iris pigmented epithelial cells (iPECs) reprogram into a lens, a tissue that is derived from a different embryonic ... ...

    Abstract Lens regeneration in the adult newt illustrates a unique example of naturally occurring cell transdifferentiation. During this process, iris pigmented epithelial cells (iPECs) reprogram into a lens, a tissue that is derived from a different embryonic source. Several methodologies both in vivo and in culture have been utilized over the years to observe this phenomenon. Most recently, Optical Coherence Tomography (OCT) has been identified as an effective tool to study the lens regeneration process in continuity through noninvasive, real-time imaging of the same animal. Described in this chapter are three different methodologies that can be used to observe the newt lens regeneration process both in vivo and ex vivo.
    MeSH term(s) Animals ; Lens, Crystalline ; Salamandridae ; Cell Transdifferentiation ; Epithelial Cells
    Language English
    Publishing date 2022-10-21
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
    ISSN 1940-6029
    ISSN (online) 1940-6029
    DOI 10.1007/978-1-0716-2659-7_13
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Isolation and Characterization of Peritoneal Macrophages from Salamanders.

    Sallese, Anthony / Tsissios, Georgios / Pérez-Estrada, J Raúl / Martinez, Arielle / Del Rio-Tsonis, Katia

    Methods in molecular biology (Clifton, N.J.)

    2022  Volume 2562, Page(s) 259–270

    Abstract: Salamanders have been used as research models for centuries. While they exhibit a wide range of biological features not seen in mammals, none has captivated scientists like their ability to regenerate. Interestingly, axolotl macrophages have emerged as ... ...

    Abstract Salamanders have been used as research models for centuries. While they exhibit a wide range of biological features not seen in mammals, none has captivated scientists like their ability to regenerate. Interestingly, axolotl macrophages have emerged as an essential cell population for tissue regeneration. Whether the same is true in other salamanders such as newt species Notophthalmus viridescens, Cynops pyrrhogaster, or Pleurodeles waltl remains to be seen. Unfortunately, regardless of the species, molecular tools to study macrophage function in salamanders are lacking. We propose that the readily available, terminally differentiated peritoneal macrophages from newts or axolotls could be used to validate molecular reagents in the study of macrophage function during tissue regeneration in salamanders.
    MeSH term(s) Animals ; Urodela ; Macrophages, Peritoneal ; Pleurodeles ; Mammals ; Salamandridae
    Language English
    Publishing date 2022-10-19
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
    ISSN 1940-6029
    ISSN (online) 1940-6029
    DOI 10.1007/978-1-0716-2659-7_18
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article: DISTINCT METABOLIC STATES DIRECT RETINAL PIGMENT EPITHELIUM CELL FATE DECISIONS.

    Perez-Estrada, J Raúl / Tangeman, Jared A / Proto-Newton, Maeve / Sanaka, Harshavardhan / Smucker, Byran / Del Rio-Tsonis, Katia

    bioRxiv : the preprint server for biology

    2023  

    Abstract: During tissue regeneration, proliferation, dedifferentiation, and reprogramming are necessary to restore lost structures. However, it is not fully understood how metabolism intersects with these processes. Chicken embryos can regenerate their retina ... ...

    Abstract During tissue regeneration, proliferation, dedifferentiation, and reprogramming are necessary to restore lost structures. However, it is not fully understood how metabolism intersects with these processes. Chicken embryos can regenerate their retina through retinal pigment epithelium (RPE) reprogramming when treated with fibroblast factor 2 (FGF2). Using transcriptome profiling, we uncovered extensive regulation of gene sets pertaining to proliferation, neurogenesis, and glycolysis throughout RPE-to-neural retina reprogramming. By manipulating cell media composition, we determined that glucose, glutamine, or pyruvate are sufficient to support RPE reprogramming identifying glycolysis as a requisite. Conversely, the induction of oxidative metabolism by activation of pyruvate dehydrogenase induces Epithelial-to-mesenchymal transition (EMT), while simultaneously blocking the activation of neural retina fate. We also identify that EMT is partially driven by an oxidative environment. Our findings provide evidence that metabolism controls RPE cell fate decisions and provide insights into the metabolic state of RPE cells, which are prone to fate changes in regeneration and pathologies, such as proliferative vitreoretinopathy.
    Language English
    Publishing date 2023-09-27
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2023.09.26.559631
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Correction to: An application of slow feature analysis to the genetic sequences of coronaviruses and influenza viruses.

    Tsonis, Anastasios A / Wang, Geli / Zhang, Lvyi / Lu, Wenxu / Kayafas, Aristotle / Del Rio-Tsonis, Katia

    Human genomics

    2021  Volume 15, Issue 1, Page(s) 31

    Language English
    Publishing date 2021-06-02
    Publishing country England
    Document type Published Erratum
    ZDB-ID 2147618-4
    ISSN 1479-7364 ; 1479-7364
    ISSN (online) 1479-7364
    ISSN 1479-7364
    DOI 10.1186/s40246-021-00334-3
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Integrated single-cell multiomics uncovers foundational regulatory mechanisms of lens development and pathology.

    Tangeman, Jared A / Rebull, Sofia M / Grajales-Esquivel, Erika / Weaver, Jacob M / Bendezu-Sayas, Stacy / Robinson, Michael L / Lachke, Salil A / Del Rio-Tsonis, Katia

    Development (Cambridge, England)

    2024  Volume 151, Issue 1

    Abstract: 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 ... ...

    Abstract 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.
    MeSH term(s) Humans ; Multiomics ; Cataract/genetics ; Cell Differentiation/genetics ; Eye ; Lens, Crystalline
    Language English
    Publishing date 2024-01-05
    Publishing country England
    Document type Journal Article
    ZDB-ID 90607-4
    ISSN 1477-9129 ; 0950-1991
    ISSN (online) 1477-9129
    ISSN 0950-1991
    DOI 10.1242/dev.202249
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  6. Article ; Online: Design and Characterization of Biomimetic Kerateine Aerogel-Electrospun Polycaprolactone Scaffolds for Retinal Cell Culture.

    Zeng, Ziqian / Lam, Phuong T / Robinson, Michael L / Del Rio-Tsonis, Katia / Saul, Justin M

    Annals of biomedical engineering

    2021  Volume 49, Issue 7, Page(s) 1633–1644

    Abstract: Age-related macular degeneration (AMD) is a retinal disease that affects 196 million people and causes nearly 9% of blindness worldwide. While several pharmacological approaches slow the effects of AMD, in our opinion, cell-based strategies offer the ... ...

    Abstract Age-related macular degeneration (AMD) is a retinal disease that affects 196 million people and causes nearly 9% of blindness worldwide. While several pharmacological approaches slow the effects of AMD, in our opinion, cell-based strategies offer the most likely path to a cure. We describe the design and initial characterization of a kerateine (obtained by reductive extraction from keratin proteins) aerogel-electrospun polycaprolactone fiber scaffold system. The scaffolds mimic key features of the choroid and the Bruch's membrane, which is the basement membrane to which the cells of the retinal pigment epithelium (RPE) attach. The scaffolds had elastic moduli of 2-7.2 MPa, a similar range as native choroid and Bruch's membrane. ARPE-19 cells attached to the polycaprolactone fibers, remained viable for one week, and proliferated to form a monolayer reminiscent of that needed for retinal repair. These constructs could serve as a model system for testing cell and/or drug treatment strategies or directing ex vivo retinal tissue formation in the treatment of AMD.
    MeSH term(s) Biomimetic Materials/chemistry ; Cell Culture Techniques ; Cell Line ; Humans ; Keratins/chemistry ; Polyesters/chemistry ; Retinal Pigment Epithelium/metabolism ; Tissue Scaffolds/chemistry
    Chemical Substances Polyesters ; polycaprolactone (24980-41-4) ; Keratins (68238-35-7)
    Language English
    Publishing date 2021-04-06
    Publishing country United States
    Document type Journal Article
    ZDB-ID 185984-5
    ISSN 1573-9686 ; 0191-5649 ; 0090-6964
    ISSN (online) 1573-9686
    ISSN 0191-5649 ; 0090-6964
    DOI 10.1007/s10439-021-02756-5
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article: Integrated single-cell multiomics uncovers foundational regulatory mechanisms of lens development and pathology.

    Tangeman, Jared A / Rebull, Sofia M / Grajales-Esquivel, Erika / Weaver, Jacob M / Bendezu-Sayas, Stacy / Robinson, Michael L / Lachke, Salil A / Rio-Tsonis, Katia Del

    bioRxiv : the preprint server for biology

    2023  

    Abstract: 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 ...

    Abstract 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
    Language English
    Publishing date 2023-07-11
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2023.07.10.548451
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: An application of slow feature analysis to the genetic sequences of coronaviruses and influenza viruses.

    Tsonis, Anastasios A / Wang, Geli / Zhang, Lvyi / Lu, Wenxu / Kayafas, Aristotle / Del Rio-Tsonis, Katia

    Human genomics

    2021  Volume 15, Issue 1, Page(s) 26

    Abstract: Background: Mathematical approaches have been for decades used to probe the structure of DNA sequences. This has led to the development of Bioinformatics. In this exploratory work, a novel mathematical method is applied to probe the DNA structure of two ...

    Abstract Background: Mathematical approaches have been for decades used to probe the structure of DNA sequences. This has led to the development of Bioinformatics. In this exploratory work, a novel mathematical method is applied to probe the DNA structure of two related viral families: those of coronaviruses and those of influenza viruses. The coronaviruses are SARS-CoV-2, SARS-CoV-1, and MERS. The influenza viruses include H1N1-1918, H1N1-2009, H2N2-1957, and H3N2-1968.
    Methods: The mathematical method used is the slow feature analysis (SFA), a rather new but promising method to delineate complex structure in DNA sequences.
    Results: The analysis indicates that the DNA sequences exhibit an elaborate and convoluted structure akin to complex networks. We define a measure of complexity and show that each DNA sequence exhibits a certain degree of complexity within itself, while at the same time there exists complex inter-relationships between the sequences within a family and between the two families. From these relationships, we find evidence, especially for the coronavirus family, that increasing complexity in a sequence is associated with higher transmission rate but with lower mortality.
    Conclusions: The complexity measure defined here may hold a promise and could become a useful tool in the prediction of transmission and mortality rates in future new viral strains.
    MeSH term(s) Betacoronavirus/classification ; Betacoronavirus/genetics ; Betacoronavirus/physiology ; Coronavirus Infections/mortality ; Coronavirus Infections/transmission ; Coronavirus Infections/virology ; Evolution, Molecular ; Humans ; Influenza A virus/classification ; Influenza A virus/genetics ; Influenza A virus/physiology ; Influenza, Human/mortality ; Influenza, Human/transmission ; Influenza, Human/virology ; Models, Genetic ; Sequence Analysis, DNA ; Species Specificity ; Time Factors
    Language English
    Publishing date 2021-05-07
    Publishing country England
    Document type Journal Article
    ZDB-ID 2147618-4
    ISSN 1479-7364 ; 1479-7364
    ISSN (online) 1479-7364
    ISSN 1479-7364
    DOI 10.1186/s40246-021-00327-2
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  9. Article: Generation of a Retina Reporter hiPSC Line to Label Progenitor, Ganglion, and Photoreceptor Cell Types.

    Lam, Phuong T / Gutierrez, Christian / Del Rio-Tsonis, Katia / Robinson, Michael L

    Translational vision science & technology

    2020  Volume 9, Issue 3, Page(s) 21

    Abstract: Purpose: Early in mammalian eye development, : Methods: CRISPR/Cas9-mediated homology-directed repair (HDR) in hiPSCs facilitated the replacement of the : Results: Retinal organoids formed from the PGP1 line expressed appropriate fluorescent ... ...

    Abstract Purpose: Early in mammalian eye development,
    Methods: CRISPR/Cas9-mediated homology-directed repair (HDR) in hiPSCs facilitated the replacement of the
    Results: Retinal organoids formed from the PGP1 line expressed appropriate fluorescent proteins consistent with the differentiation of NRPs, RGCs, and PRs. Organoids produced from the PGP1 line expressed transcripts consistent with the development of all major retinal cell types.
    Conclusions and translational relevance: The PGP1 line offers a powerful new tool to study retinal development, retinal reprogramming, and therapeutic drug screening.
    MeSH term(s) Animals ; Cell Differentiation ; Humans ; Induced Pluripotent Stem Cells ; Organoids ; Photoreceptor Cells ; Retina
    Language English
    Publishing date 2020-02-18
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 2674602-5
    ISSN 2164-2591
    ISSN 2164-2591
    DOI 10.1167/tvst.9.3.21
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  10. Article ; Online: Characterizing the lens regeneration process in Pleurodeles waltl.

    Tsissios, Georgios / Theodoroudis-Rapp, Gabriella / Chen, Weihao / Sallese, Anthony / Smucker, Byran / Ernst, Lake / Chen, Junfan / Xu, Yiqi / Ratvasky, Sophia / Wang, Hui / Del Rio-Tsonis, Katia

    Differentiation; research in biological diversity

    2023  Volume 132, Page(s) 15–23

    Abstract: Background: Aging and regeneration are heavily linked processes. While it is generally accepted that regenerative capacity declines with age, some vertebrates, such as newts, can bypass the deleterious effects of aging and successfully regenerate a lens ...

    Abstract Background: Aging and regeneration are heavily linked processes. While it is generally accepted that regenerative capacity declines with age, some vertebrates, such as newts, can bypass the deleterious effects of aging and successfully regenerate a lens throughout their lifetime.
    Results: Here, we used Spectral-Domain Optical Coherence Tomography (SD-OCT) to monitor the lens regeneration process of larvae, juvenile, and adult newts. While all three life stages were able to regenerate a lens through transdifferentiation of the dorsal iris pigment epithelial cells (iPECs), an age-related change in the kinetics of the regeneration process was observed. Consistent with these findings, iPECs from older animals exhibited a delay in cell cycle re-entry. Furthermore, it was observed that clearance of the extracellular matrix (ECM) was delayed in older organisms.
    Conclusions: Collectively, our results suggest that although lens regeneration capacity does not decline throughout the lifespan of newts, the intrinsic and extrinsic cellular changes associated with aging alter the kinetics of this process. By understanding how these changes affect lens regeneration in newts, we can gain important insights for restoring the age-related regeneration decline observed in most vertebrates.
    MeSH term(s) Animals ; Pleurodeles ; Salamandridae ; Lens, Crystalline ; Extracellular Matrix ; Cell Division
    Language English
    Publishing date 2023-03-11
    Publishing country England
    Document type Journal Article
    ZDB-ID 184540-8
    ISSN 1432-0436 ; 0301-4681
    ISSN (online) 1432-0436
    ISSN 0301-4681
    DOI 10.1016/j.diff.2023.02.003
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