A genomic-based approach identifies FXYD domain containing ion transport regulator 2 (FXYD2)γa as a pancreatic beta cell-specific biomarker

Flamez, Daisy; Roland, Isabelle; Berton, Alix; Kutlu, Burak; Dufrane, Denis; Beckers, Marie-Claire; Waele, Evelien De; Rooman, Ilse; Bouwens, Luc; Clark, Andrew E.; Lonneux, Max; Jamar, J F; Goldman, Serge; Maréchal, Daniel; Goodman, Nathan; Gianello, Pierre; Huffel, Christophe Van; Salmon, Isabelle; Eizirik, Décio L.

doi:10.1007/s00125-010-1714-z

Cited by 40 publications

(52 citation statements)

References 38 publications

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“…This would also validate that the antibody beads were binding intact exosomes. The transmembrane protein ion channel regulator FXYD2 isoforms γa and γb is reported to be an islet β cell-specific surface marker compared with exocrine pancreas (19)(20)(21)(22). Therefore, we assessed for FXYD2 surface coexpression Figure 4B).…”

Section: Transplanted Human Islets Release Donor Mhc-specific Exosomementioning

confidence: 99%

Tissue-specific exosome biomarkers for noninvasively monitoring immunologic rejection of transplanted tissue

Vallabhajosyula¹,

Korutla²,

Habertheuer³

et al. 2017

Journal of Clinical Investigation

144

138

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Section: Transplanted Human Islets Release Donor Mhc-specific Exosomementioning

confidence: 99%

Tissue-specific exosome biomarkers for noninvasively monitoring immunologic rejection of transplanted tissue

Vallabhajosyula¹,

Korutla²,

Habertheuer³

et al. 2017

Journal of Clinical Investigation

144

138

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“…Cell surface markers or marker combinations for beta-cells exist, but they will also label immature insulinpositive cells early in development [117][118][119]. At the moment, there are no cell surface markers that specifically label mature beta-cells.…”

Section: Low Overall Efficiency Of Differentiationmentioning

confidence: 99%

Maturation of Stem Cell-Derived Beta-cells Guided by the Expression of Urocortin 3

Meulen¹,

Huising²

2014

Rev Diabet Stud

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■ AbstractType 1 diabetes (T1D) is a devastating disease precipitated by an autoimmune response directed at the insulinproducing beta-cells of the pancreas for which no cure exists. Stem cell-derived beta-cells show great promise for a cure as they have the potential to supply unlimited numbers of cells that could be derived from a patient's own cells, thus eliminating the need for immunosuppression. Current in vitro protocols for the differentiation of stem cell-derived beta-cells can successfully generate pancreatic endoderm cells. In diabetic rodents, such cells can differentiate further along the beta-cell lineage until they are eventually capable of restoring normoglycemia. While these observations demonstrate that stem cell-derived pancreatic endoderm has the potential to differentiate into mature, glucose-responsive beta-cells, the signals that direct differentiation and maturation from pancreatic endoderm onwards remain poorly understood. In this review, we analyze the sequence of events that culminates in the formation of beta-cells during embryonic development, and we summarize how current protocols to generate beta-cells have sought to capitalize on this ontogenic template. We place particular emphasis on the current challenges and opportunities which occur in the later stages of beta-cell differentiation and maturation of transplantable stem cell-derived beta-cells. Another focus is on the question how the use of recently identified maturation markers such as urocortin 3 can be instrumental in guiding these efforts.

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“…The wide implementation of these technologies is hindered by the lack of established and 502792J HCXXX10.1369/0022155413502792Kavishwar and MooreSphingomyelin Patches and Insulin Secretion research-article2013 validated specific markers on the beta-cell surface. The several markers that have been described so far (GAD (Baekkeskov et al 1990), carboxipeptidase H (Castano et al 1991), ICA69 (Pietropaolo et al 1993), VMAT-2 (Maffei et al 2004;Pettibone et al 1984), GLP-1R (Reiner et al 2011;Wicki et al 2007), SUR-1 (Schneider et al 2005), FXYD2 (Flamez et al 2010), TMEM27 (Vats et al 2012) and scFv's from phage display libraries (Ueberberg et al 2009) still require validation in animal models (for review see (Kavishwar and Moore 2012)). Importantly, these markers do not reflect beta-cell function, which is a serious drawback when an evaluation of therapeutic efficacy is needed.…”

Section: Introductionmentioning

confidence: 99%

Sphingomyelin Patches on Pancreatic Beta-cells Are Indicative of Insulin Secretory Capacity

Kavishwar

Moore

2013

J Histochem Cytochem.

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The establishment and validation of specific markers on the surfaces of pancreatic beta-cells would have a significant impact on the development of agents that specifically target these cells for imaging and/or image-guided therapy in diabetes patient samples. We have recently described unique, cholesterol-stabilized sphingomyelin (SM) patches on the surfaces of beta-cells using the IC2 antibody. To further investigate the utility of SM patches as a unique beta-cell biomarker, we embarked on the current study to correlate the expression of this antigen with the insulin secretory capacity of beta-cells in tissue samples from patients and animals with type 1 and type 2 diabetes and compared this with samples from normal subjects. We found that the locations of SM patches were consistent with the insulin status of islets in all tissues studied. Using immunohistochemistry and staining with an IC2 antibody, we demonstrated a direct correlation between the reduced expression of SM patches and insulin production in diabetic individuals, indicating that the former could potentially serve as a functional biomarker of beta-cells. We believe that our results have significant implications for the further development of ligands with SM specificity for the non-invasive functional assessment of beta-cells and/or for targeted therapeutic delivery in diabetic patients.

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A genomic-based approach identifies FXYD domain containing ion transport regulator 2 (FXYD2)γa as a pancreatic beta cell-specific biomarker

Cited by 40 publications

References 38 publications

Tissue-specific exosome biomarkers for noninvasively monitoring immunologic rejection of transplanted tissue

Tissue-specific exosome biomarkers for noninvasively monitoring immunologic rejection of transplanted tissue

Maturation of Stem Cell-Derived Beta-cells Guided by the Expression of Urocortin 3

Sphingomyelin Patches on Pancreatic Beta-cells Are Indicative of Insulin Secretory Capacity

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