Sexual dimorphisms in adult human neural, mesoderm‐derived, and neural crest‐derived stem cells

Greiner, Johannes F. W.; Merten, Madlen; Kaltschmidt, Christian; Kaltschmidt, Barbara

doi:10.1002/1873-3468.13606

Cited by 18 publications

(23 citation statements)

References 106 publications

(257 reference statements)

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“…In particular, female donors of similar age (female donor II: 67 y, female donor III: 61 y) revealed a significant difference in the amounts of Nestin, S100, Slug and NF-κB protein. In addition, the interpopulational heterogeneity in marker expression shown here was not attributed to potential sexual dimorphisms, which are increasingly noticed to drive heterogeneous behavior of NCSCs and other adult stem cells ( 20 reviewed in 32 ). We therefor suggest genetic variations between the distinct donors to account for the observed differences in NCSC-marker expression between the analyzed ITSC-populations, which will be assessed in more detail in future work.…”

Section: Discussionmentioning

confidence: 68%

Inter- and Intrapopulational Heterogeneity of Characteristic Markers in Adult Human Neural Crest-Derived Stem Cells

Windmöller

Höving

Greiner

2021

Preprint

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Adult human neural crest-derived stem cells (NCSCs) are found in a variety of adult tissues and show an extraordinary broad developmental potential. NCSCs are therefore promising candidates for applications in regenerative medicine, although increasing evidence suggest a remaining nichedependent variability between different NCSC-populations regarding their behavior and expression signatures. In the present study, we extended the view on heterogeneity of NCSCs by identifying heterogeneous expression levels and protein amounts of characteristic markers even between NCSCs from the same niche of origin. In particular, populations of neural crest-derived inferior turbinate stem cells (ITSCs) isolated from different individuals showed significant variations in characteristic NCSC marker proteins Nestin, S100 and Slug in a donor-dependent manner. Notably, increased nuclear protein amounts of Slug were accompanied by a significantly elevated level of nuclear NF-κB-p65 protein, suggesting an NF-κB-dependent regulation of NCSC-makers. In addition to this interpopulational genetic heterogeneity of ITSC-populations from different donors, single ITSCs also revealed a strong heterogeneity regarding the protein amounts of Nestin, S100, Slug and NF-κB-p65 even within the same clonal culture. Our present findings therefor strongly suggest ITSC-heterogeneity to be at least partly based on an interpopulational genetic heterogeneity dependent on the donor accompanied by a stochastic intrapopulational heterogeneity between single cells. We propose this stochastic intrapopulational heterogeneity to occur in addition to the already described genetic variability between clonal NCSC-cultures and the niche-dependent plasticity of NCSCs. Our observations offer a novel perspective on NCSC-heterogeneity, which may build the basis to understand heterogeneous NCSC-behavior and improve their clinical applicability.

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Section: Discussionmentioning

confidence: 68%

Inter- and Intrapopulational Heterogeneity of Characteristic Markers in Adult Human Neural Crest-Derived Stem Cells

Windmöller

Höving

Greiner

2021

Preprint

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show abstract

Section: Discussionmentioning

confidence: 69%

Inter- and intrapopulational heterogeneity of characteristic markers in adult human neural crest-derived stem cells

Windmoeller

Hoeving

Greiner

2021

Preprint

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Adult human neural crest-derived stem cells (NCSCs) are found in a variety of adult tissues and show an extraordinary broad developmental potential. NCSCs are therefore promising candidates for applications in regenerative medicine, although increasing evidence suggest a remaining niche-dependent variability between different NCSC-populations regarding their behavior and expression signatures. In the present study, we extended the view on heterogeneity of NCSCs by identifying heterogeneous expression levels and protein amounts of characteristic markers even between NCSCs from the same niche of origin. In particular, populations of neural crest-derived inferior turbinate stem cells (ITSCs) isolated from different individuals showed significant variations in characteristic NCSC marker proteins Nestin, S100 and Slug in a donor-dependent manner. Notably, increased nuclear protein amounts of Slug were accompanied by a significantly elevated level of nuclear NF-κB-p65 protein, suggesting an NF-κB-dependent regulation of NCSC-makers. In addition to this interpopulational genetic heterogeneity of ITSC-populations from different donors, single ITSCs also revealed a strong heterogeneity regarding the protein amounts of Nestin, S100, Slug and NF-κB-p65 even within the same clonal culture. Our present findings therefor strongly suggest ITSC-heterogeneity to be at least partly based on an interpopulational genetic heterogeneity dependent on the donor accompanied by a stochastic intrapopulational heterogeneity between single cells. We propose this stochastic intrapopulational heterogeneity to occur in addition to the already described genetic variability between clonal NCSC-cultures and the niche-dependent plasticity of NCSCs. Our observations offer a novel perspective on NCSC-heterogeneity, which may build the basis to understand heterogeneous NCSC-behavior and improve their clinical applicability.

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“…Additionally, our findings should be interpreted with caution when generalizing to both male and females, given that this is a female cell line. Research shows sexual dimorphism in cognition (Ycaza Herrera et al, 2019), caffeine metabolism (Adan et al, 2008;Denden et al, 2016) and neurogenesis (Greiner et al, 2019).…”

Section: Discussionmentioning

confidence: 99%

Caffeine Compromises Proliferation of Human Hippocampal Progenitor Cells

Houghton

Preez

Lefèvre‐Arbogast

et al. 2020

Front. Cell Dev. Biol.

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The age-associated reduction in the proliferation of neural stem cells (NSCs) has been associated with cognitive decline. Numerous factors have been shown to modulate this process, including dietary components. Frequent consumption of caffeine has been correlated with an increased risk of cognitive decline, but further evidence of a negative effect on hippocampal progenitor proliferation is limited to animal models. Here, we used a human hippocampal progenitor cell line to investigate the effects of caffeine on hippocampal progenitor integrity and proliferation specifically. The effects of five caffeine concentrations (0 mM = control, 0.1 mM ∼ 150 mg, 0.25 mM ∼ 400 mg, 0.5 mM ∼ 750 mg, and 1.0 mM ∼ 1500 mg) were measured following acute (1 day) and repeated (3 days) exposure. Immunocytochemistry was used to quantify hippocampal progenitor integrity (i.e., SOX2-and Nestin-positive cells), proliferation (i.e., Ki67-positive cells), cell count (i.e., DAPI-positive cells), and apoptosis (i.e., CC3-positive cells). We found that progenitor integrity was significantly reduced in supraphysiological caffeine conditions (i.e., 1.0 mM ∼ 1500 mg), but relative to the lowest caffeine condition (i.e., 0.1 mM ∼ 150 mg) only. Moreover, repeated exposure to supraphysiological caffeine concentrations (i.e., 1.0 mM ∼ 1500 mg) was found to affect proliferation, significantly reducing % Ki67-positive cells relative to control and lower caffeine dose conditions (i.e., 0.1 mM ∼ 150 mg and 0.25 mM ∼ 400 mg). Caffeine treatment did not influence apoptosis and there were no significant differences in any measure between lower doses of caffeine (i.e., 0.1 mM, 0.25 mM, 0.5 mM)-representative of daily human caffeine intake-and control conditions. Our study demonstrates that dietary components such as caffeine can influence NSC integrity and proliferation and may be indicative of a mechanism by which diet affects cognitive outcomes.

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Sexual dimorphisms in adult human neural, mesoderm‐derived, and neural crest‐derived stem cells

Cited by 18 publications

References 106 publications

Inter- and Intrapopulational Heterogeneity of Characteristic Markers in Adult Human Neural Crest-Derived Stem Cells

Inter- and Intrapopulational Heterogeneity of Characteristic Markers in Adult Human Neural Crest-Derived Stem Cells

Inter- and intrapopulational heterogeneity of characteristic markers in adult human neural crest-derived stem cells

Caffeine Compromises Proliferation of Human Hippocampal Progenitor Cells

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