Department of Cell Biology, University of Bielefeld, Bielefeld, Germany.
Forschungsverbund BioMedizin Bielefeld FBMB e.V, Bielefeld, Germany.
Stem Cell Rev Rep. 2022 Apr;18(4):1510-1520. doi: 10.1007/s12015-021-10277-w. Epub 2021 Nov 8.
Adult human neural crest-derived stem cells (NCSCs) are found in a variety of adult tissues and show an extraordinary broad developmental potential. Despite their great differentiation capacity, increasing evidence suggest a remaining niche-dependent variability between different NCSC-populations regarding their differentiation 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.
成人神经嵴源性干细胞（NCSCs）存在于多种成人组织中，表现出非凡的广泛发育潜能。尽管它们具有巨大的分化能力，但越来越多的证据表明，不同 NCSC 群体之间在其分化行为和表达特征方面仍然存在着依赖于龛位的可变性。在本研究中，我们通过鉴定特征性标记物的不均匀表达水平和蛋白含量，甚至在来自同一起源龛位的 NCSC 之间，进一步扩展了 NCSC 异质性的观点。特别是，从不同个体分离的神经嵴源性下鼻甲干细胞（ITSCs）群体在供体依赖性方面表现出特征性 NCSC 标记蛋白 Nestin、S100 和 Slug 的显著变化。值得注意的是，Slug 的核蛋白含量增加伴随着核 NF-κB-p65 蛋白水平的显著升高，表明 NCSC 标志物的 NF-κB 依赖性调节。除了不同供体来源的 ITSC 群体之间的这种种群间遗传异质性外，单个 ITSC 甚至在同一克隆培养物中也表现出 Nestin、S100、Slug 和 NF-κB-p65 蛋白含量的强烈异质性。因此，我们目前的研究结果强烈表明，ITSC 的异质性至少部分是基于供体依赖性的种群间遗传异质性，并伴有单细胞之间的随机种群内异质性。我们提出这种随机的种群内异质性除了已经描述的克隆 NCSC 培养物之间的遗传变异性和 NCSC 的龛位依赖性可塑性之外。我们的观察结果为 NCSC 异质性提供了一个新的视角，这可能为理解异质性 NCSC 行为提供基础。
