Human Blood Serum Induces p38-MAPK- and Hsp27-Dependent Migration Dynamics of Adult Human Cardiac Stem Cells: Single-Cell Analysis via a Microfluidic-Based Cultivation Platform

Greiner

2021

Cells

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NF-κB (nuclear factor kappa B) belongs to a family of transcription factors known to regulate a broad range of processes such as immune cell function, proliferation and cancer, neuroprotection, and long-term memory. Upcoming fields of NF-κB research include its role in stem cells and developmental processes. In the present review, we discuss one role of NF-κB in development in Drosophila, Xenopus, mice, and humans in accordance with the concept of evo-devo (evolutionary developmental biology). REL domain-containing proteins of the NF-κB family are evolutionarily conserved among these species. In addition, we summarize cellular phenotypes such as defective B- and T-cell compartments related to genetic NF-κB defects detected among different species. While NF-κB proteins are present in nearly all differentiated cell types, mouse and human embryonic stem cells do not contain NF-κB proteins, potentially due to miRNA-dependent inhibition. However, the mesodermal and neuroectodermal differentiation of mouse and human embryonic stem cells is hampered upon the repression of NF-κB. We further discuss NF-κB as a crucial regulator of differentiation in adult stem cells such as neural crest-derived and mesenchymal stem cells. In particular, c-REL seems to be important for neuronal differentiation and the neuroprotection of human adult stem cells, while RELA plays a crucial role in osteogenic and mesodermal differentiation.

Section: Regulatory Roles Of Nf-κb In Driving Differentiation Of Neural Crest-derived Stem Cellsmentioning

confidence: 87%

The Transcription Factor NF-κB in Stem Cells and Development

Greiner

2021

Cells

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“…However, the cultivation method utilized here was previously demonstrated to assure genetic stability and stemness of ITSCs [19], thus minimizing potential extrinsic influences. Moreover, we recently observed an intrapopulational heterogeneity within the migration behavior of NC-derived hCSCs, even when utilizing a microfluidic cultivation system to minimize culture-dependent extrinsic stimuli [44].…”

Section: Discussionmentioning

confidence: 99%

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

Windmöller

Höving

Knabbe

et al. 2021

Stem Cell Rev and Rep

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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. 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

“…Hoving et al isolated human CSCs (hCSCs) from the cultured tissue debris in a CSC medium and characterized their migration behavior in human serum. They found that CSC migration caused by human serum was inhibited by a p-38 MAPK inhibitor [ 108 ]. We isolated these cells in a similar manner, but by using a c-kit antibody after collecting the cells which were migrated from the tissue debris, and obtained multipotent stem cells [ 109 ], which were used for differentiation analysis [ 110 ].…”

Section: Somatic Stem Cellsmentioning

confidence: 99%

Stem Cell Studies in Cardiovascular Biology and Medicine: A Possible Key Role of Macrophages

Kawaguchi

Nakanishi

2022

Biology

Stem cells are used in cardiovascular biology and biomedicine, and research in this field is expanding. Two types of stem cells have been used in research: induced pluripotent and somatic stem cells. Stem cell research in cardiovascular medicine has developed rapidly following the discovery of different types of stem cells. Induced pluripotent stem cells (iPSCs) possess potent differentiation ability, unlike somatic stem cells, and have been postulated for a long time. However, differentiating into adult-type mature and functional cardiac myocytes (CMs) remains difficult. Bone marrow stem/stromal cells (BMSCs), adipose-derived stem cells (ASCs), and cardiac stem cells (CSCs) are somatic stem cells used for cardiac regeneration. Among somatic stem cells, bone marrow stem/stromal cells (BMSCs) were the first to be discovered and are relatively well-characterized. BMSCs were once thought to have differentiation ability in infarcted areas of the heart, but it has been identified that paracrine cytokines and micro-RNAs derived from BMSCs contributed to that effect. Moreover, vesicles and exosomes from these cells have similar effects and are effective in cardiac repair. The molecular signature of exosomes can also be used for diagnostics because exosomes have the characteristics of their origin cells. Cardiac stem cells (CSCs) differentiate into cardiomyocytes, smooth muscle cells, and endothelial cells, and supply cardiomyocytes during myocardial infarction by differentiating into newly formed cardiomyocytes. Stem cell niches and inflammatory cells play important roles in stem cell regulation and the recovery of damaged tissues. In particular, chemokines can contribute to the communication between inflammatory cells and stem cells. In this review, we present the current status of this exciting and promising research field.