Patterns of Wnt pathway activity in the mouse incisor indicate absence of Wnt/β-catenin signaling in the epithelial stem cells

2009 ◽  
pp. NA-NA ◽  
Author(s):  
Marika Suomalainen ◽  
Irma Thesleff
2010 ◽  
Vol 80 (4-5) ◽  
pp. 241-248 ◽  
Author(s):  
Szabolcs Felszeghy ◽  
Marika Suomalainen ◽  
Irma Thesleff

2013 ◽  
Vol 19 (1) ◽  
pp. 15-24 ◽  
Author(s):  
Miquella G. Chavez ◽  
Wenli Yu ◽  
Brian Biehs ◽  
Hidemitsu Harada ◽  
Malcolm L. Snead ◽  
...  

2020 ◽  
Author(s):  
David Melamed ◽  
Daniel Kalderon

AbstractMany adult stem cells are maintained as a community by population asymmetry, wherein stochastic actions of individual cells collectively result in a balance between stem cell division and differentiation. We have used Drosophila Follicle Stem Cells (FSCs) as a paradigm to explore the extracellular niche signals that define a stem cell domain and organize stem cell behavior. FSCs produce transit-amplifying Follicle Cells (FCs) from their posterior face and quiescent Escort Cells (ECs) to their anterior. Here we show that JAK-STAT pathway activity, which declines from posterior to anterior, dictates the pattern of divisions over the FSC and EC domains, promotes more posterior FSC locations and conversion to FCs, while opposing EC production. A Wnt pathway gradient of opposite polarity promotes more anterior FSC locations and EC production and opposes FC production. Promotion of both FSC division and conversion to FCs by JAK-STAT signaling buffers the effects of genetically altered pathway activity on FSC numbers and balances the four-fold higher rate of differentiation at the posterior face of the FSC domain with a higher rate of FSC division in the most posterior layer. However, genetic elimination of Wnt pathway activity exacerbated elevated FC production resulting from increased JAK-STAT pathway activity, leading to rapid FSC depletion despite high rates of division. The two pathways combine to define a stem cell domain through concerted effects on FSC differentiation to ECs (high Wnt, low JAK-STAT) and FCs (low Wnt, high JAK-STAT) at each end of opposing signaling gradients, further enforced by quiescence at the anterior border due to declining JAK-STAT pathway activity.


1999 ◽  
Vol 147 (1) ◽  
pp. 105-120 ◽  
Author(s):  
Hidemitsu Harada ◽  
Päivi Kettunen ◽  
Han-Sung Jung ◽  
Tuija Mustonen ◽  
Y. Alan Wang ◽  
...  

The continuously growing mouse incisor is an excellent model to analyze the mechanisms for stem cell lineage. We designed an organ culture method for the apical end of the incisor and analyzed the epithelial cell lineage by 5-bromo-2′-deoxyuridine and DiI labeling. Our results indicate that stem cells reside in the cervical loop epithelium consisting of a central core of stellate reticulum cells surrounded by a layer of basal epithelial cells, and that they give rise to transit-amplifying progeny differentiating into enamel forming ameloblasts. We identified slowly dividing cells among the Notch1-expressing stellate reticulum cells in specific locations near the basal epithelial cells expressing lunatic fringe, a secretory molecule modulating Notch signaling. It is known from tissue recombination studies that in the mouse incisor the mesenchyme regulates the continuous growth of epithelium. Expression of Fgf-3 and Fgf-10 were restricted to the mesenchyme underlying the basal epithelial cells and the transit-amplifying cells expressing their receptors Fgfr1b and Fgfr2b. When FGF-10 protein was applied with beads on the cultured cervical loop epithelium it stimulated cell proliferation as well as expression of lunatic fringe. We present a model in which FGF signaling from the mesenchyme regulates the Notch pathway in dental epithelial stem cells via stimulation of lunatic fringe expression and, thereby, has a central role in coupling the mitogenesis and fate decision of stem cells.


Author(s):  
Miquella G. Chavez ◽  
Jimmy Hu ◽  
Kerstin Seidel ◽  
Chunying Li ◽  
Andrew Jheon ◽  
...  

2021 ◽  
Author(s):  
Yvonne Wesseling-Rozendaal ◽  
Laurent Holtzer ◽  
Wim Verhaegh ◽  
Anja van de Stolpe

AbstractStem cell research is emerging both as a scientifically and clinically relevant area. One of the current challenges in stem cell research and regenerative medicine is assessment of the pluripotency state of induced pluripotent stem (iPS) cells. Once a stem cell differentiation process is initiated the challenge is how to assess the state of differentiation, and the purity of the differentiated cell population. Stem cell potency and differentiation states are determined by tightly coordinated activity of developmental signaling pathways, such as the Notch, Hedgehog, TGFβ, Wnt, PI3K, MAPK-AP1, and NFκB pathways. Source of the stem cells and culture protocols may influence stem cell phenotype, with potential consequences for pluripotency and in general for experimental reproducibility. Human pluripotent embryonic (hES) and iPS stem cell lines under different culture conditions, organ derived multipotent stem cells, and differentiated cell types, were phenotyped with respect to functional activity of developmental signaling pathways.MethodsWe previously reported on the development and validation of a novel assay platform for quantitative measurement of activity of multiple signal transduction pathways (STP) simultaneously in a single sample, based on interpreting a preselected set of target mRNA expression levels. Assays were used to calculate Notch, Hedgehog, TGFβ, Wnt, PI3K, MAPK-AP1, and NFκB signal transduction pathway activity scores for individual cell samples, using publicly available Affymetrix expression microarray data.ResultsCulture conditions (e.g. mouse versus human feeder) influenced pluripotent stem cell pathway activity profiles. hES and iPS stem cell lines cultured in the same lab under similar conditions showed minimal variation in pathway activity profile despite different genetic backgrounds, while across different labs larger variations were measured, even for the same stem cell line. Pathway activity scores for PI3K, MAPK, Hedgehog, Notch, TGFβ, and NFκB pathways rapidly decreased upon pluripotent stem cell differentiation, while increasing for the Wnt pathway. Further differentiation to intestinal progenitor cells resulted in higher PI3K, Wnt and Notch pathway activity. In multipotent intestinal crypt stem cells obtained from intestinal mucosa samples, similar Notch and even higher Wnt pathway activity were measured, which disappeared upon differentiation to mucosal cells.ConclusionResults support the validity of using these STP assays for quantitative phenotyping of stem cells and differentiated derivatives, and enabled definition of a pluripotency profile with high PI3K, MAPK, Hedgehog, TGFβ, Notch, and NFκB, and low Wnt pathway activity scores.Measurement of combined signaling pathway activity scores is expected to improve experimental reproducibility and standardization of pluripotent and multipotent stem cell culture and differentiation. It enables controlled manipulation of signaling pathway activity using pathway targeting compounds. An envisioned additional utility may lie in quality control for regenerative medicine purposes.


eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
David Melamed ◽  
Daniel Kalderon

Many adult stem cell communities are maintained by population asymmetry, where stochastic behaviors of multiple individual cells collectively result in a balance between stem cell division and differentiation. We investigated how this is achieved for Drosophila Follicle Stem Cells (FSCs) by spatially-restricted niche signals. FSCs produce transit-amplifying Follicle Cells (FCs) from their posterior face and quiescent Escort Cells (ECs) to their anterior. We show that JAK-STAT pathway activity, which declines from posterior to anterior, dictates the pattern of divisions over the FSC domain, promotes more posterior FSC locations and conversion to FCs, while opposing EC production. Wnt pathway activity declines from the anterior, promotes anterior FSC locations and EC production, and opposes FC production. The pathways combine to define a stem cell domain through concerted effects on FSC differentiation to ECs and FCs at either end of opposing signaling gradients, and impose a pattern of proliferation that matches derivative production.


Oncotarget ◽  
2017 ◽  
Vol 8 (70) ◽  
pp. 115254-115269 ◽  
Author(s):  
Chaolin Huang ◽  
Yuanhong Chen ◽  
Hang Liu ◽  
Jing Yang ◽  
Xuejing Song ◽  
...  

2015 ◽  
Vol 6 ◽  
Author(s):  
Giovanna Orsini ◽  
Lucia Jimenez-Rojo ◽  
Despoina Natsiou ◽  
Angelo Putignano ◽  
Thimios A. Mitsiadis

2012 ◽  
Vol 366 (2) ◽  
pp. 357-366 ◽  
Author(s):  
Chun-Ying Li ◽  
Wanghee Cha ◽  
Hans-Ulrich Luder ◽  
Roch-Philippe Charles ◽  
Martin McMahon ◽  
...  

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