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Journal ArticleDOI: 10.1016/J.STEM.2020.11.002

Differentiated Daughter Cells Regulate Stem Cell Proliferation and Fate through Intra-tissue Tension

04 Mar 2021-Cell Stem Cell (Elsevier)-Vol. 28, Iss: 3
Abstract: Basal stem cells fuel development, homeostasis, and regeneration of the epidermis. The proliferation and fate decisions of these cells are highly regulated by their microenvironment, including the basement membrane and underlying mesenchymal cells. Basal progenitors give rise to differentiated progeny that generate the epidermal barrier. Here, we present data that differentiated progeny also regulate the proliferation, differentiation, and migration of basal progenitor cells. Using two distinct mouse lines, we found that increasing contractility of differentiated cells resulted in non-cell-autonomous hyperproliferation of stem cells and prevented their commitment to a hair follicle lineage. This increased contractility also impaired movement of basal progenitors during hair placode morphogenesis and diminished migration of melanoblasts. These data suggest that intra-tissue tension regulates stem cell proliferation, fate decisions, and migration and that differentiated epidermal keratinocytes are a component of the stem cell niche that regulates development and homeostasis of the skin.

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Topics: Stem cell (61%), Cellular differentiation (60%), Progenitor cell (59%) ... read more
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6 results found


Open accessJournal ArticleDOI: 10.1242/DEV.199669
15 Sep 2021-Development
Abstract: Skin expansion during development is predominantly driven by growth of basal epithelial cell (BEC)-derived clonal populations, which often display varied sizes and shapes. However, little is known about the causes of clonal heterogeneity and the maximum size to which a single clone can grow. Here, we created a zebrafish model, basebow, for capturing clonal growth behavior in the BEC population on a whole-body, centimeter scale. By tracking 222 BECs over the course of a 28-fold expansion of body surface area, we determined that most BECs survive and grow clonal populations with an average size of 0.013 mm2. An extensive survey of 742 sparsely labeled BECs further revealed that giant dominant clones occasionally arise on specific body regions, covering up to 0.6% of the surface area. Additionally, a growth-induced extracellular matrix component, Lamb1a, mediates clonal growth in a cell-autonomous manner. Altogether, our findings demonstrate how clonal heterogeneity and clonal dominance may emerge to enable post-embryonic growth of a vertebrate organ, highlighting key cellular mechanisms that may only become evident when visualizing single cell behavior at the whole animal level.

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Topics: Extracellular matrix component (54%), Body region (54%), Population (52%) ... read more

1 Citations


Open accessJournal ArticleDOI: 10.15252/EMBJ.2020106787
15 Jun 2021-The EMBO Journal
Abstract: Eukaryotic development relies on dynamic cell shape changes and segregation of fate determinants to achieve coordinated compartmentalization at larger scale. Studies in invertebrates have identified polarity programmes essential for morphogenesis; however, less is known about their contribution to adult tissue maintenance. While polarity-dependent fate decisions in mammals utilize molecular machineries similar to invertebrates, the hierarchies and effectors can differ widely. Recent studies in epithelial systems disclosed an intriguing interplay of polarity proteins, adhesion molecules and mechanochemical pathways in tissue organization. Based on major advances in biophysics, genome editing, high-resolution imaging and mathematical modelling, the cell polarity field has evolved to a remarkably multidisciplinary ground. Here, we review emerging concepts how polarity and cell fate are coupled, with emphasis on tissue-scale mechanisms, mechanobiology and mammalian models. Recent findings on the role of polarity signalling for tissue mechanics, micro-environmental functions and fate choices in health and disease will be summarized.

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Topics: Polarity (physics) (58%), Cell polarity (56%)

1 Citations


Journal ArticleDOI: 10.1016/J.DEVCEL.2021.01.003
Flora Llense1, Michel Labouesse1Institutions (1)
25 Jan 2021-Developmental Cell
Abstract: Most tissues include several cell types, which generally develop or get repaired synchronously so as to remain properly organized. In a recent Cell Stem Cell article, Ning et al. (2020) reveals how the tensile state of the skin suprabasal cells non-autonomously regulate stem cell behavior in the basal layer.

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Open accessJournal ArticleDOI: 10.1016/J.STEM.2021.02.012
04 Mar 2021-Cell Stem Cell
Abstract: In this issue of Cell Stem Cell, Ning et al. (2021) demonstrate that contractility in differentiating, suprabasally located keratinocytes acts non-cell-autonomously to regulate the replication and differentiation of the stem/progenitor keratinocytes in the basal layer of epidermis. This finding expands our understanding of the niche that regulates stem/progenitor cells in skin.

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Topics: Progenitor cell (64%), Stem cell (62%), Epidermis (botany) (54%)

Journal ArticleDOI: 10.1016/J.SEMCDB.2021.09.008
Abstract: Stratified epithelia are made up of several layers of cells, which act as a protective barrier for the organ they cover. To ensure their shielding effect, epithelia are naturally able to cope with constant environmental insults. This ability is enabled by their morphology and architecture, as well as the continuous turnover of stem and progenitor cells that constitute their building blocks. Stem cell fate decisions and dynamics are fundamental key biological processes that allow epithelia to exert their functions. By focusing on the skin epidermis, this review discusses how tissue architecture is generated during development, maintained through adult life, and re-established during regeneration.

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Topics: Tissue homeostasis (56%), Stem cell (54%), Progenitor cell (52%) ... read more

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69 results found


Open accessJournal ArticleDOI: 10.1073/PNAS.0506580102
Abstract: Although genomewide RNA expression analysis has become a routine tool in biomedical research, extracting biological insight from such information remains a major challenge. Here, we describe a powerful analytical method called Gene Set Enrichment Analysis (GSEA) for interpreting gene expression data. The method derives its power by focusing on gene sets, that is, groups of genes that share common biological function, chromosomal location, or regulation. We demonstrate how GSEA yields insights into several cancer-related data sets, including leukemia and lung cancer. Notably, where single-gene analysis finds little similarity between two independent studies of patient survival in lung cancer, GSEA reveals many biological pathways in common. The GSEA method is embodied in a freely available software package, together with an initial database of 1,325 biologically defined gene sets.

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26,320 Citations


Open accessJournal ArticleDOI: 10.1126/SCIENCE.1116995
18 Nov 2005-Science
Abstract: Normal tissue cells are generally not viable when suspended in a fluid and are therefore said to be anchorage dependent. Such cells must adhere to a solid, but a solid can be as rigid as glass or softer than a baby's skin. The behavior of some cells on soft materials is characteristic of important phenotypes; for example, cell growth on soft agar gels is used to identify cancer cells. However, an understanding of how tissue cells-including fibroblasts, myocytes, neurons, and other cell types-sense matrix stiffness is just emerging with quantitative studies of cells adhering to gels (or to other cells) with which elasticity can be tuned to approximate that of tissues. Key roles in molecular pathways are played by adhesion complexes and the actinmyosin cytoskeleton, whose contractile forces are transmitted through transcellular structures. The feedback of local matrix stiffness on cell state likely has important implications for development, differentiation, disease, and regeneration.

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Topics: Durotaxis (55%), Cancer cell (52%), Cell adhesion (51%) ... read more

5,408 Citations


Open accessJournal ArticleDOI: 10.1016/S0092-8674(04)00255-7
19 Mar 2004-Cell
Abstract: The potential of stem cells in regenerative medicine relies upon removing them from their natural habitat, propagating them in culture, and placing them into a foreign tissue environment. To do so, it is essential to understand how stem cells interact with their microenvironment, the so-called stem cell niche, to establish and maintain their properties. In this review, we examine adult stem cell niches and their impact on stem cell biology.

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Topics: Adult stem cell (63%), Stem cell (62%), Regenerative medicine (52%)

1,776 Citations


Open accessJournal ArticleDOI: 10.1038/NRM2786
Abstract: Non-muscle myosin II (NM II) is an actin-binding protein that has actin cross-linking and contractile properties and is regulated by the phosphorylation of its light and heavy chains. The three mammalian NM II isoforms have both overlapping and unique properties. Owing to its position downstream of convergent signalling pathways, NM II is central in the control of cell adhesion, cell migration and tissue architecture. Recent insight into the role of NM II in these processes has been gained from loss-of-function and mutant approaches, methods that quantitatively measure actin and adhesion dynamics and the discovery of NM II mutations that cause monogenic diseases.

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Topics: Myosin light-chain kinase (60%), Myosin (60%), Cell adhesion (56%) ... read more

1,571 Citations


Open accessJournal ArticleDOI: 10.1016/J.CELL.2010.09.016
01 Oct 2010-Cell
Abstract: SUMMARY Intestinal stem cells, characterized by high Lgr5 expression, reside between Paneth cells at the small intestinal crypt base and divide every day. We have carried out fate mapping of individual stem cells by

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Topics: Stem cell (59%), Adult stem cell (57%), Crypt (53%) ... read more

1,521 Citations


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20216