Insulin-like Growth Factor-II (IGF-II) and IGF-II Analogs with Enhanced Insulin Receptor-a Binding Affinity Promote Neural Stem Cell Expansion

Ziegler, Amber N.; Chidambaram, Shravanthi; Forbes, Briony E.; Wood, Teresa L.; Levison, Steven W.

doi:10.1074/jbc.m113.537597

Cited by 50 publications

(65 citation statements)

References 38 publications

(51 reference statements)

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“…83,84 More contemporary studies, including those by our group (reviewed in the next section), have described roles for IGF-II in NSC maintenance and neural progenitor expansion. 8,10,85–87 IGF-II produced by fibroblasts regulates human ESC self-renewal and survival through the IGF-I receptor. 88 Similarly, pluripotency of murine ESCs depends, in part, on regulation of IGF-II expression by sonic hedgehog.…”

Section: Igfs and Stem Cellsmentioning

confidence: 99%

Section: Igfs and Neural Stem Cellsmentioning

confidence: 99%

“…87,105 By use of a blocking antibody to the IGF-I receptor, the effects of IGF-2 Phe19Ala on NSCs were shown to be independent of the IGF-I receptor. 87,105 Additionally, neurospheres demonstrated little to no growth when only the IGF-II receptor was stimulated (using another mutated IGF-II protein, with a Val43Met substitution). 87,105 Furthermore, IR-A is more highly expressed than the IGF-I receptor within the medial SVZ, which contains the NSC niche; conversely, the IGF-I receptor is more highly expressed than IR-A in the lateral SVZ, which is a progenitor-cell domain of the SVZ (Figure 3).…”

Section: Igfs and Neural Stem Cellsmentioning

confidence: 99%

“…87,105 Additionally, neurospheres demonstrated little to no growth when only the IGF-II receptor was stimulated (using another mutated IGF-II protein, with a Val43Met substitution). 87,105 Furthermore, IR-A is more highly expressed than the IGF-I receptor within the medial SVZ, which contains the NSC niche; conversely, the IGF-I receptor is more highly expressed than IR-A in the lateral SVZ, which is a progenitor-cell domain of the SVZ (Figure 3). 8 IR-A is also the predominant isoform expressed in neurospheres and, as cells become lineage-restricted, the levels of IR-A decrease.…”

Section: Igfs and Neural Stem Cellsmentioning

confidence: 99%

“…110 IGF-II also reduced amyloid levels in transgenic mice overexpressing amyloid precursor protein, and the reduction in levels of amyloid in cells in vitro was dependent on the IGF-II receptor. Although cell culture studies have demonstrated that IGF-II functions via IR-A to promote self-renewal and expansion of rodent SVZ NSCs, 8,87 the effects of IGF-II are probably not limited to a single receptor or a single interaction. A complex interplay that depends on cell type, location and the expression profile of the IGF-II receptor probably determines the outcome of IGF-II actions on the different NSC and progenitor cell populations.…”

Section: Igfs and Neural Stem Cellsmentioning

confidence: 99%

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Insulin and IGF receptor signalling in neural-stem-cell homeostasis

2014

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Neural stem cells (NSCs) are found in two regions in the adult brain: the subgranular zone (SGZ) in the hippocampal dentate gyrus and the subventricular zone (SVZ) adjacent to the lateral ventricles. Similarly to other somatic stem cells, adult NSCs are found within specialized niches that are organized to facilitate NSC self-renewal. Alterations in stem-cell homeostasis can contribute to the consequences of neurodegenerative diseases, healthy ageing and tissue repair after damage. Insulin and the insulin-like growth factors (IGFs) function in stem-cell homeostasis across species. Studies in the mammalian central nervous system support essential roles for IGF and/or insulin signalling in NSC self-renewal, neurogenesis, cognition and sensory function through distinct ligand–receptor interactions. IGF-II is of particular interest as a result of its production by the choroid plexus and presence in cerebrospinal fluid (CSF). CSF regulates and supports the development, division and migration of cells in the adult brain and is required for NSC maintenance. In this Review, we discuss emerging data on the functions of IGF-II and IGF and/or insulin receptor signalling in the context of NSC regulation in the SVZ and SGZ. We also propose a model for IGF-II in which the choroid plexus is a major component of the NSC niche.

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Section: Igfs and Stem Cellsmentioning

confidence: 99%

Section: Igfs and Neural Stem Cellsmentioning

confidence: 99%

Section: Igfs and Neural Stem Cellsmentioning

confidence: 99%

Section: Igfs and Neural Stem Cellsmentioning

confidence: 99%

Section: Igfs and Neural Stem Cellsmentioning

confidence: 99%

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Insulin and IGF receptor signalling in neural-stem-cell homeostasis

2014

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Insulin receptor isoforms: an integrated view focused on gestational diabetes mellitus

Westermeier

Sáez

Arroyo

et al. 2015

Diabetes Metabolism Res

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SummaryThe human insulin receptor (IR) exists in two isoforms that differ by the absence (IR-A) or the presence (IR-B) of a 12-amino acid segment encoded by exon 11. Both isoforms are functionally distinct regarding their binding affinities and intracellular signalling. However, the underlying mechanisms related to their cellular functions in several tissues are only partially understood. In this review, we summarize the current knowledge in this field regarding the alternative splicing of IR isoform, tissue-specific distribution and signalling both in physiology and disease, with an emphasis on the human placenta in gestational diabetes mellitus (GDM). Furthermore, we discuss the clinical relevance of IR isoforms highlighted by findings that show altered insulin signalling due to differential IR-A and IR-B expression in human placental endothelium in GDM pregnancies. Future research and clinical studies focused on the role of IR isoform signalling might provide novel therapeutic targets for treating GDM to improve the adverse maternal and neonatal outcomes.

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Probing early heart development to instruct stem cell differentiation strategies

Calderon

Bardot

Dubois

2016

Developmental Dynamics

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Scientists have studied organs and their development for centuries, and along that path described models and mechanisms explaining the developmental principles of organogenesis. In particular, with respect to the heart, new fundamental discoveries are reported continuously, that keep changing the way we think about early cardiac development. These discoveries are driven by the need to answer long-standing questions regarding the origin of the earliest cells specified to the cardiac lineage, the differentiation potential of distinct cardiac progenitor cells and, importantly, the molecular mechanisms underlying these specification events. As evidenced by numerous examples the wealth of developmental knowledge collected over the years has had an invaluable impact on establishing efficient strategies to generate cardiovascular cell types ex vivo, from either pluripotent stem cells or via direct reprogramming approaches. The ability to generate functional cardiovascular cells in an efficient and reliable manner will contribute to therapeutic strategies aimed at alleviating the increasing burden of cardiovascular disease and morbidity. Here we will discuss the recent discoveries in the field of cardiac progenitor biology and their translation to the pluripotent stem cell model to illustrate how developmental concepts have instructed regenerative model systems in the past and promise to do so in the future.

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Insulin-like Growth Factor-II (IGF-II) and IGF-II Analogs with Enhanced Insulin Receptor-a Binding Affinity Promote Neural Stem Cell Expansion

Cited by 50 publications

References 38 publications

Insulin and IGF receptor signalling in neural-stem-cell homeostasis

Insulin and IGF receptor signalling in neural-stem-cell homeostasis

Insulin receptor isoforms: an integrated view focused on gestational diabetes mellitus

Probing early heart development to instruct stem cell differentiation strategies

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