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Article ; Online: MAPK Pathways in Ocular Pathophysiology: Potential Therapeutic Drugs and Challenges.

Moustardas, Petros / Aberdam, Daniel / Lagali, Neil

2023 Volume 12, Issue 4

Abstract: Mitogen-activated protein kinase (MAPK) pathways represent ubiquitous cellular signal transduction pathways that regulate all aspects of life and are frequently altered in disease. Once activated through phosphorylation, these MAPKs in turn phosphorylate ...

Abstract	Mitogen-activated protein kinase (MAPK) pathways represent ubiquitous cellular signal transduction pathways that regulate all aspects of life and are frequently altered in disease. Once activated through phosphorylation, these MAPKs in turn phosphorylate and activate transcription factors present either in the cytoplasm or in the nucleus, leading to the expression of target genes and, as a consequence, they elicit various biological responses. The aim of this work is to provide a comprehensive review focusing on the roles of MAPK signaling pathways in ocular pathophysiology and the potential to influence these for the treatment of eye diseases. We summarize the current knowledge of identified MAPK-targeting compounds in the context of ocular diseases such as macular degeneration, cataract, glaucoma and keratopathy, but also in rare ocular diseases where the cell differentiation, proliferation or migration are defective. Potential therapeutic interventions are also discussed. Additionally, we discuss challenges in overcoming the reported eye toxicity of some MAPK inhibitors.
MeSH term(s)	Mitogen-Activated Protein Kinases/metabolism ; p38 Mitogen-Activated Protein Kinases/metabolism ; Signal Transduction ; Phosphorylation ; MAP Kinase Signaling System/physiology
Chemical Substances	Mitogen-Activated Protein Kinases (EC 2.7.11.24) ; p38 Mitogen-Activated Protein Kinases (EC 2.7.11.24)
Language	English
Publishing date	2023-02-14
Publishing country	Switzerland
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't
ZDB-ID	2661518-6
ISSN	2073-4409 ; 2073-4409
ISSN (online)	2073-4409
ISSN	2073-4409
DOI	10.3390/cells12040617
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Nouvelle voie métabolique de la pluripotence--Lien entre glycolyse (effet Warburg), acétyl-CoA et acétylation des histones.

Aberdam, Daniel

Medecine sciences : M/S

2015 Volume 31, Issue 6-7, Page(s) 581–583

Title translation	Metabolic switch in pluripotent stem cells: identification of a novel pathway.
MeSH term(s)	Acetyl Coenzyme A/physiology ; Animals ; Cell Differentiation/genetics ; Embryonic Stem Cells/metabolism ; Embryonic Stem Cells/physiology ; Genes, Switch ; Glycolysis/genetics ; Humans ; Metabolic Networks and Pathways/genetics ; Oxidative Phosphorylation ; Pluripotent Stem Cells/metabolism ; Pluripotent Stem Cells/physiology
Chemical Substances	Acetyl Coenzyme A (72-89-9)
Language	French
Publishing date	2015-06
Publishing country	France
Document type	News
ZDB-ID	632733-3
ISSN	1958-5381 ; 0767-0974
ISSN (online)	1958-5381
ISSN	0767-0974
DOI	10.1051/medsci/20153106002
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Article ; Online: Production and Limbal Lineage Commitment of Aniridia Patient-Derived Induced Pluripotent Stem Cells.

Ilmarinen, Tanja / Vattulainen, Meri / Kandhavelu, Jeyalakshmi / Bremond-Gignac, Dominique / Aberdam, Daniel / Skottman, Heli

Stem cells (Dayton, Ohio)

2023 Volume 41, Issue 12, Page(s) 1133–1141

Abstract: Congenital aniridia is caused by heterozygous mutations on the PAX6 gene leading to reduced amount of PAX6 protein (haploinsufficiency), abnormal eye development, and aniridia-associated keratopathy (AAK). This progressive corneal opacification resembles ...

Abstract	Congenital aniridia is caused by heterozygous mutations on the PAX6 gene leading to reduced amount of PAX6 protein (haploinsufficiency), abnormal eye development, and aniridia-associated keratopathy (AAK). This progressive corneal opacification resembles late-onset limbal stem cell (LSC) deficiency, leading to disrupted corneal epithelial renewal. The factors leading to AAK are not known and defects in native LSC differentiation and/or features leading to ocular surface dysfunction like inflammation and loss of innervation could contribute to development of AAK. Here, we produced induced pluripotent stem cells (hiPSC) from 3 AAK patients and examined whether PAX6 haploinsufficiency affects LSC lineage commitment. During LSC differentiation, characterization of the AAK lines showed lowered PAX6 expression as compared to wild type (WT) controls and expression peak of PAX6 during early phase of differentiation was detected only in the WT hiPSC lines. Whether it reflects developmental regulation remains to be studied further. Nevertheless, the AAK-hiPSCs successfully differentiated toward LSC lineage, in line with the presence of LSCs in young patients before cell loss later in life. In addition, patient-specific LSCs showed similar wound healing capacity as WT cells. However, extensive batch-related variation in the LSC marker expression and wound healing efficacy was detected without clear correlation to AAK. As development and maintenance of corneal epithelium involves an interplay between LSCs and their environment, the AAK-hiPSCs generated here can be further used to study the crosstalk between LSCs and limbal niche including, eg, corneal immune cells, stroma cells, and neurons.
MeSH term(s)	Humans ; Induced Pluripotent Stem Cells ; Cornea ; Epithelium, Corneal/metabolism ; Corneal Diseases/genetics ; PAX6 Transcription Factor/genetics ; PAX6 Transcription Factor/metabolism ; Aniridia/genetics ; Limbus Corneae
Chemical Substances	PAX6 Transcription Factor
Language	English
Publishing date	2023-08-22
Publishing country	England
Document type	Journal Article
ZDB-ID	1143556-2
ISSN	1549-4918 ; 1066-5099
ISSN (online)	1549-4918
ISSN	1066-5099
DOI	10.1093/stmcls/sxad067
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Article ; Online: Purification of Extracellular Microvesicles Secreted by Dermal Fibroblasts.

Petit, Isabelle / Levy, Ayelet / Aberdam, Daniel

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

2020 Volume 2154, Page(s) 63–72

Abstract: Extracellular vesicles (EVs) secreted by all cells are key players in information transfer within a tissue or organism. With their highly cell-specific protein and RNA content, EVs can propagate cellular signals and modulate distant cells' behavior. ... ...

Abstract	Extracellular vesicles (EVs) secreted by all cells are key players in information transfer within a tissue or organism. With their highly cell-specific protein and RNA content, EVs can propagate cellular signals and modulate distant cells' behavior. Dermal fibroblasts are supportive cells for all skin cells and the roles of their EVs start to come to light only recently. In this chapter, we describe a protocol to isolate small EVs from primary human fibroblast culture using classical differential centrifugation methodology.
MeSH term(s)	Cell Fractionation/methods ; Cell-Derived Microparticles/metabolism ; Exosomes/metabolism ; Extracellular Vesicles/metabolism ; Fibroblasts/cytology ; Fibroblasts/metabolism ; Humans ; Skin/cytology ; Ultracentrifugation
Language	English
Publishing date	2020-04-20
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	1940-6029
ISSN (online)	1940-6029
DOI	10.1007/978-1-0716-0648-3_6
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Article ; Online: PRIMA-1

Berthy, Clément / Gagnoux-Palacios, Laurent / Madrange, Marine / Bodemer, Christine / Cagnard, Nicolas / Hadj-Rabia, Smail / Petit, Isabelle / Aberdam, Daniel

The Journal of investigative dermatology

2023 Volume 144, Issue 3, Page(s) 717–719

MeSH term(s)	Humans ; Epidermolysis Bullosa, Junctional/genetics ; Epidermolysis Bullosa, Junctional/metabolism ; Cell Adhesion ; Skin/metabolism ; Epidermal Cells/metabolism ; Epidermolysis Bullosa/genetics
Language	English
Publishing date	2023-09-16
Publishing country	United States
Document type	Journal Article
ZDB-ID	80136-7
ISSN	1523-1747 ; 0022-202X
ISSN (online)	1523-1747
ISSN	0022-202X
DOI	10.1016/j.jid.2023.08.021
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Article ; Online: miR-184 represses β-catenin and behaves as a skin tumor suppressor.

Turovsky, Lubov / Kheshaiboun, Ghazal / Yassen, Gharam / Nagosa, Sara / Boyango, Ilanit / Amitai-Lange, Aya / Bhattacharya, Swarnabh / Ilan, Neta / Vlodavsky, Israel / Aberdam, Daniel / Shalom-Feuerstein, Ruby / Avitan-Hersh, Emily

Cell death & disease

2024 Volume 15, Issue 2, Page(s) 174

Abstract: miR-184-knockout mice display perturbed epidermal stem cell differentiation. However, the potential role of miR-184 in skin pathology is unclear. Here, we report that miR-184 controls epidermal stem cell dynamics and that miR-184 ablation enhances skin ... ...

Abstract	miR-184-knockout mice display perturbed epidermal stem cell differentiation. However, the potential role of miR-184 in skin pathology is unclear. Here, we report that miR-184 controls epidermal stem cell dynamics and that miR-184 ablation enhances skin carcinogenesis in mice. In agreement, repression of miR-184 in human squamous cell carcinoma (SCC) enhances neoplastic hallmarks of human SCC cells in vitro and tumor development in vivo. Characterization of miR-184-regulatory network, suggests that miR-184 inhibits pro-oncogenic pathways, cell proliferation, and epithelial to mesenchymal transformation. Of note, depletion of miR-184 enhances the levels of β-catenin under homeostasis and following experimental skin carcinogenesis. Finally, the repression of β-catenin by miR-184, inhibits the neoplastic phenotype of SCC cells. Taken together, miR-184 behaves as an epidermal tumor suppressor, and may provide a potentially useful target for skin SCC therapy.
MeSH term(s)	Animals ; Humans ; Mice ; beta Catenin/genetics ; beta Catenin/metabolism ; Carcinogenesis/genetics ; Carcinoma, Squamous Cell/pathology ; Cell Line, Tumor ; Cell Movement/genetics ; Cell Proliferation/genetics ; Gene Expression Regulation, Neoplastic/genetics ; MicroRNAs/genetics ; MicroRNAs/metabolism ; Skin Neoplasms/genetics ; Skin Neoplasms/pathology
Chemical Substances	beta Catenin ; MicroRNAs ; MIRN184 microRNA, human ; CTNNB1 protein, mouse ; MIRN184 microRNA, mouse
Language	English
Publishing date	2024-02-26
Publishing country	England
Document type	Journal Article
ZDB-ID	2541626-1
ISSN	2041-4889 ; 2041-4889
ISSN (online)	2041-4889
ISSN	2041-4889
DOI	10.1038/s41419-024-06554-4
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Article ; Online: Epidermal stem cell fate: what can we learn from embryonic stem cells?

Aberdam, Daniel

Cell and tissue research

2008 Volume 331, Issue 1, Page(s) 103–107

Abstract: Because of its constant renewal and high propensity for repair, the epidermis is, together with the gut and the hematopoietic system, a tissue of choice to explore stem cell biology. Previous research over many years has revealed the complexity of the ... ...

Abstract	Because of its constant renewal and high propensity for repair, the epidermis is, together with the gut and the hematopoietic system, a tissue of choice to explore stem cell biology. Previous research over many years has revealed the complexity of the epidermis: the heterogeneity of the stem cell compartment, with its rare, slowly cycling, multipotent, hair-follicle, "bulge" stem cells and the more restricted interfollicular, follicle-matrix, and sebaceous-gland stem cells, which in turn generate the large pool of transit-amplifying progeny. Stem cell activity has been used for some considerable time to repair skin injuries, but ex-vivo keratinocyte amplification has its limitations, and grafted skin homeostasis is not totally satisfactory. Human embryonic stem cells raise the hope that the understanding of the developmental steps leading to the generation of epidermal stem cells and the characterization of the key signaling pathways involved in skin morphogenesis (such as p63) will be translated into therapeutic benefit. Our recent results suggest the feasibility not only of identifying but also of amplifying human ES cells, early ectodermal progenitors with an intact multipotent potential that might improve the quality and functionality of grafts, provided that preclinical in vivo studies confirm our expectations from in vitro analysis.
MeSH term(s)	Animals ; Cell Lineage ; Cell- and Tissue-Based Therapy ; Embryonic Stem Cells/cytology ; Embryonic Stem Cells/metabolism ; Epidermis/cytology ; Epidermis/metabolism ; Humans ; Skin/cytology ; Skin/embryology
Language	English
Publishing date	2008-01
Publishing country	Germany
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	125067-x
ISSN	1432-0878 ; 0302-766X
ISSN (online)	1432-0878
ISSN	0302-766X
DOI	10.1007/s00441-007-0497-0
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Article: Réparer ou régénérer, il faut choisir...

Aberdam, Daniel

Medecine sciences : M/S

2007 Volume 23, Issue 10, Page(s) 791–793

Title translation	To repair or to regenerate, it is necessary to choose....
MeSH term(s)	Alopecia/pathology ; Alopecia/therapy ; Animals ; Epidermis/cytology ; Hair Follicle/cytology ; Hair Follicle/embryology ; Hair Follicle/physiology ; Humans ; Mice ; Mice, Transgenic ; Multipotent Stem Cells/cytology ; Regeneration/physiology ; Species Specificity ; Wnt Proteins/physiology ; Wound Healing
Chemical Substances	Wnt Proteins
Language	French
Publishing date	2007-10
Publishing country	France
Document type	News
ZDB-ID	632733-3
ISSN	1958-5381 ; 0767-0974
ISSN (online)	1958-5381
ISSN	0767-0974
DOI	10.1051/medsci/20072310791
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Article ; Online: Induced pluripotent stem cell-derived limbal epithelial cells (LiPSC) as a cellular alternative for in vitro ocular toxicity testing.

Aberdam, Edith / Petit, Isabelle / Sangari, Linda / Aberdam, Daniel

PloS one

2017 Volume 12, Issue 6, Page(s) e0179913

Abstract: Induced pluripotent stem cells hold great potential to produce unlimited amount of differentiated cells as cellular source for regenerative medicine but also for in vitro drug screening and cytotoxicity tests. Ocular toxicity testing is mandatory to ... ...

Abstract	Induced pluripotent stem cells hold great potential to produce unlimited amount of differentiated cells as cellular source for regenerative medicine but also for in vitro drug screening and cytotoxicity tests. Ocular toxicity testing is mandatory to evaluate the risks of drugs and cosmetic products before their application to human patients by preventing eye irritation or insult. Since the global ban to use animals, many human-derived alternatives have been proposed, from ex-vivo enucleated postmortem cornea, primary corneal cell culture and immortalized corneal epithelial cell lines. All of them share limitations for their routine use. Using an improved protocol, we derived limbal epithelial cells from human induced pluripotent stem cells, named LiPSC, that are able to be passaged and differentiate further into corneal epithelial cells. Comparative RT-qPCR, immunofluorescence staining, flow cytometry analysis and zymography assays demonstrate that LiPSC are morphologically and molecularly similar to the adult stem cells. Moreover, contrary to HCE, LiPSC and primary limbal cells display similarly sensitive to cytotoxicity treatment among passages. Our data strongly suggest that LiPSC could become a powerful alternative cellular model for cosmetic and drug tests.
MeSH term(s)	Calcium/pharmacology ; Cell Differentiation/drug effects ; Cytotoxins/toxicity ; Epithelial Cells/cytology ; Epithelial Cells/drug effects ; Epithelial Cells/metabolism ; Humans ; Induced Pluripotent Stem Cells/cytology ; Limbus Corneae/cytology ; Matrix Metalloproteinase 9/metabolism ; Toxicity Tests/methods
Chemical Substances	Cytotoxins ; Matrix Metalloproteinase 9 (EC 3.4.24.35) ; Calcium (SY7Q814VUP)
Language	English
Publishing date	2017
Publishing country	United States
Document type	Journal Article
ISSN	1932-6203
ISSN (online)	1932-6203
DOI	10.1371/journal.pone.0179913
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Eyes open on stem cells.

Altshuler, Anna / Amitai-Lange, Aya / Nasser, Waseem / Dimri, Shalini / Bhattacharya, Swarnabh / Tiosano, Beatrice / Barbara, Ramez / Aberdam, Daniel / Shimmura, Shigeto / Shalom-Feuerstein, Ruby

Stem cell reports

2023 Volume 18, Issue 12, Page(s) 2313–2327

Abstract: Recently, the murine cornea has reemerged as a robust stem cell (SC) model, allowing individual SC tracing in living animals. The cornea has pioneered seminal discoveries in SC biology and regenerative medicine, from the first corneal transplantation in ... ...

Abstract	Recently, the murine cornea has reemerged as a robust stem cell (SC) model, allowing individual SC tracing in living animals. The cornea has pioneered seminal discoveries in SC biology and regenerative medicine, from the first corneal transplantation in 1905 to the identification of limbal SCs and their transplantation to successfully restore vision in the early 1990s. Recent experiments have exposed unexpected properties attributed to SCs and progenitors and revealed flexibility in the differentiation program and a key role for the SC niche. Here, we discuss the limbal SC model and its broader relevance to other tissues, disease, and therapy.
MeSH term(s)	Mice ; Animals ; Epithelium, Corneal ; Limbus Corneae ; Cornea ; Stem Cells ; Cell Differentiation ; Stem Cell Transplantation
Language	English
Publishing date	2023-11-30
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	2720528-9
ISSN	2213-6711 ; 2213-6711
ISSN (online)	2213-6711
ISSN	2213-6711
DOI	10.1016/j.stemcr.2023.10.023
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