Biology subjects

Greiner, J. F. W.

Publications and source records attributed to Greiner, J. F. W..

3 recordsLinked to original sources

bioRxiv2021

Human Sex Matters: Y-linked lysine demethylase 5D drives accelerated male osteogenic differentiation

Female sex is increasingly associated to a loss of bone mass during aging and an increased risk for fractures developing nonunion. Hormonal factors and cell-intrinsic mechanisms are suggested to drive these sexual dimorphisms, although underlying molecular mechanisms are still a matter of debate. Here, we observed a decreased capacity of calvarial bone recovery in female rats and a profound sexually dimorphic osteogenic differentiation human adult neural crest-derived stem cells (NCSCs). Next to an elevated expression of pro-osteogenic regulators, global trancriptomics revealed Lysine Demethylase 5D (KDM5D) to be highly upregulated in differentiating male NCSCs. Loss of function by siRNA or pharmacological inhibition of KDM5D significantly reduced the osteogenic differentiation capacity of male NCSCs. In summary, we demonstrate craniofacial osteogenic differentiation to be sexually dimorphic with the expression of KDM5D as a prerequisite for accelerated male osteogenic differentiation, emphasizing the analysis of sex-specific differences as a crucial parameter for treating bone defects.

cell biology↗

bioRxiv2021

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

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-{kappa}B-p65 protein, suggesting an NF-{kappa}B-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-{kappa}B-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.

cell biology↗

bioRxiv2019

Identification of a human adult cardiac stem cell population with neural crest origin

Cardiovascular diseases are the major cause of death worldwide, emphasizing the necessity to better understand adult human cardiac cell biology and development. Although the adult heart was considered as a terminally differentiated organ, rare populations of cardiac stem cells (CSCs) have been described so far, with their developmental origin and endogenous function still being a matter of debate.\n\nHere, we identified a Nestin+/S100+/CD105+/Sca1+/cKit- population of CSCs in the myocardium of the adult human heart auricle. Isolated cells showed expression of characteristic neural crest-derived stem cell (NCSC) markers and kept their genetic stability during cultivation in vitro. Cultivated hCSCs efficiently gave rise to functional, beating cardiomyocytes, osteoblasts, adipocytes and neurons. Global transcriptome analysis via RNAseq showed a high similarity between the expression profiles of Nestin+/S100+/CD105+/Sca1+/cKit- hCSCs and adult human NCSCs from the nasal cavity (inferior turbinate stem cells, ITSCs). In detail, 88.1 % of all genes were significantly expressed in both stem cell populations particularly including common NCSC-markers. Based on these observations, we suggest a similar developmental origin of both stem cell populations.\n\nIn summary, we identified a human adult cardiac stem cell population with neural crest-origin, which may also contribute to endogenous cardiac tissue homeostasis and tissue repair in vivo.

cell biology↗