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

Abstract

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. Graphical Abstract

Development and In Vitro Differentiation of Schwann Cells

“…We have included studies that demonstrated distinct differentiation protocols or techniques for the first time, added crucial modifications to previously published ones, or demonstrated the transfer of published protocols to another source cell type. For the latter, we have also considered the tissue origin for adult-tissue derived stem cells, as variation in differentiation potential has been shown for both MSC [ 284 ], as well as adult neural crest-derived stem cells [ 285 ], depending on the tissue they were harvested from.…”

Characteristics of Human Nasal Turbinate Stem Cells under Hypoxic Conditions

“…Derived from the human nasal inferior turbinate, human nasal inferior turbinatederived stem cells (hNTSCs) offer a conveniently accessible resource obtainable during the treatment of chronic rhinitis, and have emerged as a valuable repository of MSCs, as highlighted across various studies [11][12][13][14][15][16][17][18]. These hNTSCs exhibit a remarkable resilience to their microenvironment, showcasing an elevated potential for proliferation and consistently retaining their distinct characteristics throughout successive cell passages [19,20].…”