uu.seUppsala University Publications
Change search
ReferencesLink to record
Permanent link

Direct link
ZBED6 negatively regulates insulin production, neuronal differentiation and cell aggregation in MIN6 cells
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
(English)Manuscript (preprint) (Other academic)
National Category
Cell and Molecular Biology
URN: urn:nbn:se:uu:diva-223613OAI: oai:DiVA.org:uu-223613DiVA: diva2:713352
Available from: 2014-04-22 Created: 2014-04-22 Last updated: 2014-06-30
In thesis
1. Study of the Proliferation, Function and Death of Insulin-Producing Beta-Cells in vitro: Role of the Transcription Factor ZBED6
Open this publication in new window or tab >>Study of the Proliferation, Function and Death of Insulin-Producing Beta-Cells in vitro: Role of the Transcription Factor ZBED6
2014 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

A thorough understanding of beta-cell proliferation, function, death and regeneration under normal condition as well as in the progression of diabetes is crucial to the conquest of this disease. The work presented in this thesis aimed to investigate the expression and role of a novel transcription factor, Zinc finger BED domain-containing protein 6 (ZBED6), in beta-cells.

ZBED6 was present in mouse βTC-6 cells and human islets as a double nuclear band at 115/120 kDa and as a single cytoplasmic band at 95-100 kDa, which lacked N-terminal nuclear localization signals. Lentiviral shRNA-mediated stable silencing of ZBED6 in βTC-6 cells resulted in altered morphology, decreased proliferation, a partial S/G2 cell cycle arrest, increased expression of beta-cell specific genes, and higher rates of apoptosis. ChIP sequencing of human islets showed that ZBED6 binding was preferentially to genes that control transcription, macromolecule biosynthesis and apoptosis. We proposed that ZBED6 supported proliferation and survival of beta-cells, possibly at the expense of specialized beta-cell function, i.e. insulin production.

To further investigate the role of ZBED6 in beta-cells, ChIP sequencing and whole transcriptome analysis were performed using MIN6 cells. More than 4000 putative target genes of ZBED6 were identified, including Pdx1, MafA and Nkx6.1. ZBED6-silencing resulted in differential expression of more than 700 genes, which was paralleled by an increase in the content and release of insulin in response to a high glucose concentration. Altered morphology/growth patterns as indicated by increased cell clustering were observed in ZBED6 silenced cells. We found also that ZBED6 decreased the ratio between N- and E-cadherin. A lower N- to E-cadherin ratio may hamper the formation of three-dimensional beta-cell clusters and cell-to-cell junctions with neural crest stem cells, and instead promote efficient attachment to a laminin support and monolayer growth. Thus, by controlling beta-cell adhesion and cell-to-cell junctions, ZBED6 might play an important role in beta-cell differentiation, proliferation and survival.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2014. 53 p.
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 1002
ZBED6, Pancreatic beta-cell, Proliferation, Insulin secretion, Apoptosis, Adhesion
National Category
Medical and Health Sciences Cell and Molecular Biology
Research subject
Medical Science
urn:nbn:se:uu:diva-223616 (URN)978-91-554-8959-5 (ISBN)
Public defence
2014-06-10, A1:107a, BMC, Husargatan 3, Uppsala, 13:15 (English)
Available from: 2014-05-20 Created: 2014-04-22 Last updated: 2014-06-30

Open Access in DiVA

No full text

By organisation
Department of Medical Cell Biology
Cell and Molecular Biology

Search outside of DiVA

GoogleGoogle Scholar

Total: 196 hits
ReferencesLink to record
Permanent link

Direct link