Expression of Isl1 during mouse development

Zhuang, Shaowei; Zhang, Qingquan; Zhuang, Tao; Evans, Sylvia M.; Liang, Xingqun; Sun, Yunfu

doi:10.1016/j.gep.2013.07.001

Cited by 56 publications

(49 citation statements)

References 34 publications

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“…On day 1 and day 2 the medium was supplemented with 0.1% (v/v) and 1% (v/v) insulin-transferrin-selenium, respectively. Cells were fixed and stained against the mesodermal/endodermal marker islet-1 (38).…”

Section: Methodsmentioning

confidence: 99%

Cleavage of E-Cadherin and β-Catenin by Calpain Affects Wnt Signaling and Spheroid Formation in Suspension Cultures of Human Pluripotent Stem Cells

Konze

Diepen²,

Schröder

et al. 2014

Molecular & Cellular Proteomics

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The envisioned clinical and industrial use of human pluripotent stem cells and their derivatives has given major momentum to the establishment of suspension culture protocols that enable the mass production of cells. Understanding molecular changes accompanying the transfer from adherent to suspension culture is of utmost importance because this information can have a direct effect on the development of optimized culture conditions. In this study we assessed the gene expression of human embryonic stem cells and induced pluripotent stem cells grown in surface-adherent culture (two-dimensional) versus free-floating suspension culture spheroids (three-dimensional). We combined a quantitative proteomic approach based on stable isotope labeling by amino acids in cell culture with deep-sequencing-based transcriptomics. Cells in three-dimensional culture showed reduced expression of proteins forming structural components of cell-cell and cell-extracellular matrix junctions. However, fully unexpected, we found up-regulation of secreted inhibitors of the canonical Wnt signaling pathway and, concomitantly, a reduction in the level of active ␤-catenin and in the expression of Wnt target genes. In Western blot analyses the cysteine protease calpain was shown to cleave E-cadherin and ␤-catenin under three-dimensional culture conditions. Our data al- Human embryonic and induced pluripotent stem cells (hESCs and hiPSCs, respectively) 1 hold the potential for indefinite self-renewal and differentiation into all somatic cell types (1, 2). Beyond their application as models for studying mechanisms of pluripotency, these cells have been considered as a potent source for cell therapies and in vitro assays in pharmacology and toxicology, raising the need for largescale cell production under defined conditions (3). Conventional, surface adherent, two-dimensional culture is not suited to generate billions of human pluripotent stem cells (hPSCs) and their respective progenies required for clinical applications (3). To overcome these limits, three-dimensional culture From the ‡Institute for Cellular Chemistry, Hannover Medical School, 30625 Hannover, Germany; §REBIRTH Cluster of Excellence, Hannover Medical School, 30625 Hannover, Germany; ¶Institute for

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Section: Methodsmentioning

confidence: 99%

Cleavage of E-Cadherin and β-Catenin by Calpain Affects Wnt Signaling and Spheroid Formation in Suspension Cultures of Human Pluripotent Stem Cells

Konze

Diepen²,

Schröder

et al. 2014

Molecular & Cellular Proteomics

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“…ISL1, a LIM homeodomain transcription factor that plays an important role during cell proliferation, differentiation and survival [19], is expressed in the sinus venosus myocardium during early stages of development. Genetic lineage tracing with an inducible Isl1-Cre revealed important differences in timing of addition of cells to the developing heart and AVN.…”

Section: Introductionmentioning

confidence: 99%

The sinus venosus myocardium contributes to the atrioventricular canal: potential role during atrioventricular node development?

Kelder

Vicente‐Steijn

Harryvan

et al. 2015

J Cellular Molecular Medi

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The presence of distinct electrophysiological pathways within the atrioventricular node (AVN) is a prerequisite for atrioventricular nodal reentrant tachycardia to occur. In this study, the different cell contributions that may account for the anatomical and functional heterogeneity of the AVN were investigated. To study the temporal development of the AVN, the expression pattern of ISL1, expressed in cardiac progenitor cells, was studied in sequential stages performing co-staining with myocardial markers (TNNI2 and NKX2-5) and HCN4 (cardiac conduction system marker). An ISL1+/TNNI2+/HCN4+ continuity between the myocardium of the sinus venosus and atrioventricular canal was identified in the region of the putative AVN, which showed a pacemaker-like phenotype based on single cell patch-clamp experiments. Furthermore, qPCR analysis showed that even during early development, different cell populations can be identified in the region of the putative AVN. Fate mapping was performed by in ovo vital dye microinjection. Embryos were harvested and analysed 24 and 48 hrs post-injection. These experiments showed incorporation of sinus venosus myocardium in the posterior region of the atrioventricular canal. The myocardium of the sinus venosus contributes to the atrioventricular canal. It is postulated that the myocardium of the sinus venosus contributes to nodal extensions or transitional cells of the AVN since these cells are located in the posterior region of the AVN. This finding may help to understand the origin of atrioventricular nodal reentrant tachycardia.

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“…It consists of two N-terminal LIM domains responsible for protein interaction, a central homeodomain (HD) that binds to the specific DNA sequence and a C-terminal transactivation domain3. Isl1 expression has been reported in motor neurons4, the heart5, the digestive system6, the pituitary gland7 and the pancreas8, and Isl1 is regarded as a major transcriptional regulator in the control of pattern formation and cell specification in these tissues9.…”

mentioning

confidence: 99%

Protein Inhibitor of Activated STAT Y (PIASy) Regulates Insulin Secretion by Interacting with LIM Homeodomain Transcription Factor Isl1

Yan

Zhang

et al. 2016

Sci Rep

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It is known that the LIM homeodomain transcription factor Isl1 is highly expressed in all pancreatic endocrine cells and functions in regulating pancreatic development and insulin secretion. The Isl1 mutation has been found to be associated with type 2 diabetes, but the mechanism responsible for Isl1 regulation of insulin synthesis and secretion still needs to be elucidated. In the present study, the protein inhibitor of activated STAT Y (PIASy) was identified as a novel Isl1-interacting protein with a yeast two-hybrid system, and its interaction with Isl1 was further confirmed by a co-immunoprecipitation experiment. PIASy and Isl1 colocalize in human and mouse pancreas and NIT beta cells. Furthermore, PIASy and Isl1 upregulate insulin gene expression and insulin secretion in a dose-dependent manner by activating the insulin promoter. PIASy and Isl1 mRNA expression levels were also increased in type 2 diabetic db/db mice. In addition, our results demonstrate that PIASy and Isl1 cooperate to activate the insulin promoter through the Isl1 homeodomain and PIASy ring domain. These data suggest that that PIASy regulates insulin synthesis and secretion by interacting with Isl1 and provide new insight into insulin regulation, although the detailed molecular mechanism needs to be clarified in future studies.

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Expression of Isl1 during mouse development

Cited by 56 publications

References 34 publications

Cleavage of E-Cadherin and β-Catenin by Calpain Affects Wnt Signaling and Spheroid Formation in Suspension Cultures of Human Pluripotent Stem Cells

Cleavage of E-Cadherin and β-Catenin by Calpain Affects Wnt Signaling and Spheroid Formation in Suspension Cultures of Human Pluripotent Stem Cells

The sinus venosus myocardium contributes to the atrioventricular canal: potential role during atrioventricular node development?

Protein Inhibitor of Activated STAT Y (PIASy) Regulates Insulin Secretion by Interacting with LIM Homeodomain Transcription Factor Isl1

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