Nestin mRNA expression correlates with the central nervous system progenitor cell state in many, but not all, regions of developing central nervous system

Dahlstrand, Jonas; Lardelli, Michael; Lendahl, Urban

doi:10.1016/0165-3806(94)00162-s

Cited by 468 publications

(382 citation statements)

References 49 publications

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“…However, SOX2 expression can still provide useful insight when considered in the context of other markers such as TUJ1 and nestin. The observed pattern of nestin and SOX2 expression is consistent with the expectation that the transient expression of nestin decreases [47] and that the overall proportion of undifferentiated cells expressing SOX2 decreases [48] as the cells specialize down neuronal lineages. Interestingly, for the ESC-derived EBs, the observed decreases in nestin and SOX2 expression over this time period were not significant.…”

Section: 23supporting

confidence: 87%

Engineering personalized neural tissue by combining induced pluripotent stem cells with fibrin scaffolds

et al. 2015

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Induced pluripotent stem cells (iPSCs) are generated from adult somatic cells through the induction of key transcription factors that restore the ability to become any cell type found in the body. These cells are of interest for tissue engineering due to their potential for developing patient-specific therapies. As the technology for generating iPSCs advances, it is important to concurrently investigate protocols for the efficient differentiation of these cells to desired downstream phenotypes in combination with biomaterial scaffolds as a way of engineering neural tissue. For such applications, the generation of neurons within three dimensional fibrin scaffolds has been well characterized as a cell-delivery platform for murine embryonic stem cells (ESCs) but has not yet been applied to murine iPSCs. Given that iPSCs have been reported to differentiate less effectively than ESCs, a key objective of this investigation is to maximize the proportion of iPSC-derived neurons in fibrin through the choice of differentiation protocol. To this end, this study compares two EB-mediated protocols for generating neurons from murine iPSCs and ESCs: an 8-day 4-/4+ protocol using soluble retinoic acid in the last 4 days and a 6-day 2-/4+ protocol using soluble retinoic acid and the small molecule sonic hedgehog agonist purmorphamine in the last 4 days. EBs were then seeded in fibrin scaffolds for 14 days to allow further differentiation into neurons. EBs generated by the 2-/4+ protocol yielded a higher percentage of neurons compared to those from the 4-/4+ protocol for both iPSCs and ESCs. The results demonstrate the successful translation of the fibrin-based cell-delivery platform for use with murine iPSCs and furthermore that the proportion of neurons generated from murine iPSC-derived EBs seeded in fibrin can be maximized using the 2-/4+ differentiation protocol. Together, these findings validate the further exploration of 3D fibrin-based scaffolds as a method of delivering neuronal cells derived from iPSCs -an important step toward the development of iPSC-based tissue engineering strategies for spinal cord injury repair.

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Section: 23supporting

confidence: 87%

Engineering personalized neural tissue by combining induced pluripotent stem cells with fibrin scaffolds

et al. 2015

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“…Consistent with the fact that nestin mRNA is not expressed in proliferating areas of the developing olfactory epithelium [21], these observations imply that the 50 kDa protein rather than nestin is the tissue antigen recognized in this location. Accordingly, the 50 kDa protein may be involved in the growth and replacement of olfactory nerve fibers after losses that commonly occur in adult life.…”

Section: Discussionsupporting

confidence: 71%

Evidence for a mouse brain-specific variant of α-tubulin

et al. 1999

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While studying the neural precursor cell intermediate filament protein known as nestin in the developing mouse brain, we observed a strong cross-reaction of our nestin antibody with a 50 kDa protein that appeared on embryonic day 10 and continued to accumulate until postnatal day 1. Here we report evidence that this protein is a brain-specific variant form of α-tubulin and discuss its implications.

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“…Nestin, a type VI intermediate filament protein of the cytoskeleton, was originally found in neuroepithelial stem cells of the rat neural tube [12], [13]. Nestin expression coincided with the proliferation of these neural stem cells [14][15][16], suggesting that it plays a crucial role in cytoskeletal changes that accompany neuronal differentiation and synaptogenesis. Nestin protein is now widely used as a specific marker for neural stem cells in animals and humans [17].…”

Section: Introductionmentioning

confidence: 99%

Maternal zinc deficiency impairs brain nestin expression in prenatal and postnatal mice

et al. 2001

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Effects of maternal dietary zinc deficiency on prenatal and postnatal brain development were investigated in ICR strain mice. From d 1 of pregnancy (E0) until postnatal d 20 (P20), maternal mice were fed experimental diets that contained 1 mg Zn/kg/day (severe zinc deficient, SZD), 5 mg Zn/kg/day (marginal zinc deficient, MZD), 30 mg Zn/kg/day (zinc adequately supplied, ZA) or 100 mg Zn/kg/day (zinc supplemented, ZS and pair-fed, PF). Brains of offspring from these dietary groups were examined at various developmental stages for expression of nestin, an intermediate filament protein found in neural stem cells and young neurons. Immunocytochemistry showed nestin expression in neural tube 10.5 d post citrus (dpc) as well as in the cerebral cortex and neural tube from 10.5 dpc to postnatal d 10 (P10). Nestin immunoreactivities in both brain and neural tube of those zinc-supplemented control groups (ZA, ZS, PF) were stronger than those in zinc-deficient groups (SZD and MZD). Western blot analysis confirmed that nestin levels in pooled brain extracts from each of the zinc-supplemented groups (ZA, ZS, PF) were much higher than those from the zinc-deficient groups (SZD and MZD) from 10.5 dpc to P10. Immunostaining and Western blots showed no detectable nestin in any of the experimental and control group brains after P20. These observations of an association between maternal zinc deficiency and decreased nestin protein levels in brains of offspring suggest that zinc deficiency suppresses development of neural stem cells, an effect which may lead to neuroanatomical and behavioral abnormalities in adults.

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Nestin mRNA expression correlates with the central nervous system progenitor cell state in many, but not all, regions of developing central nervous system

Cited by 468 publications

References 49 publications

Engineering personalized neural tissue by combining induced pluripotent stem cells with fibrin scaffolds

Engineering personalized neural tissue by combining induced pluripotent stem cells with fibrin scaffolds

Evidence for a mouse brain-specific variant of α-tubulin

Maternal zinc deficiency impairs brain nestin expression in prenatal and postnatal mice

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