Stem Cell Signaling Pathways in the Small Intestine

Takahashi, Toshio; Shiraishi, Akira

doi:10.3390/ijms21062032

Cited by 45 publications

(46 citation statements)

References 123 publications

(194 reference statements)

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“…Although the capacity of tissue regeneration in mammals is progressively lost during development, several tissues and organs still maintain stem cell niches that produce progeny cells which promote tissue regeneration (Adams and Scadden, 2006;Oatley et al, 2009). Accumulating evidence also indicates that the isolation of stem cells from others tissue or organs, including the intestine, liver, and teeth, is feasible and that those stem cells can maintain the regeneration of their respective tissues under certain circumstances (Hosoya et al, 2020;Takahashi and Shiraishi, 2020). The best-characterized types of adult stem cells in mammals are hematopoietic (HSCs), neural (NSCs), mesenchymal (MSCs), and spermatogonia (SSCs) stem cells.…”

Section: Introductionmentioning

confidence: 99%

Integrated Analyses of Mouse Stem Cell Transcriptomes Provide Clues for Stem Cell Maintenance and Transdifferentiation

Wang

Hou

et al. 2020

Front. Genet.

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In vivo cell fate reprogramming has emerged as a new method for understanding cell plasticity and as potential treatment for tissue regeneration. Highly efficient and precise reprogramming requires fully understanding of the transcriptomes which function within different cell types. Here, we adopt weighted gene co-expression network analysis (WGCNA) to explore the molecular mechanisms of self-renewal in several well-known stem cell types, including embryonic stem cells (ESC), primordial germ cells (PGC), spermatogonia stem cells (SSC), neural stem cells (NSC), mesenchymal stem cells (MSC), and hematopoietic stem cells (HSC). We identified 37 core genes that were up-regulated in all of the stem cell types examined, as well as stem cell correlated gene co-expression networks. The validation of the co-expression genes revealed a continued protein-protein interaction network that included 823 nodes and 3113 edges. Based on the topology, we identified six densely connected regions within the continued protein-protein interaction network. The SSC specific genes Itgam, Cxcr6, and Agtr2 bridged four densely connected regions that consisted primarily of HSC-, NSC-, and MSC-correlated genes. The expression levels of identified stem cell related transcription factors were confirmed consistent with bioinformatics prediction in ESCs and NSCs by qPCR. Exploring the mechanisms underlying adult stem cell self-renewal will aid in the understanding of stem cell pool maintenance and will promote more accurate and efficient strategies for tissue regeneration and repair.

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Section: Introductionmentioning

confidence: 99%

Integrated Analyses of Mouse Stem Cell Transcriptomes Provide Clues for Stem Cell Maintenance and Transdifferentiation

Wang

Hou

et al. 2020

Front. Genet.

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“…The ability of ISCs to divide and differentiate is necessary for tissue repair and homeostasis. The maintenance of a functional intestine requires appropriate spatial and temporal processes involving multiple key signals from the surrounding niche [ 108 , 109 ]. The ISC niche in the small intestine is composed of stem cells and Paneth cells, and it is surrounded by mesenchymal cells at the crypt bottom [ 110 , 111 ].…”

Section: Iscs In the Adult Gutmentioning

confidence: 99%

“…Our previous pharmacological studies with crypt–villus organoids revealed that ACh is synthesized in intestinal epithelial cells and plays a role in cell division and the differentiation of Lgr5 + ISCs in the small intestine by binding to muscarinic receptors including M3 in vitro [ 23 ]. How ISC proliferation, differentiation, and maintenance are controlled and which inductive signals are required for tissue maintenance are well established [ 108 ]. However, little is known regarding the regulation of these pathways in vivo.…”

Section: Iscs In the Adult Gutmentioning

confidence: 99%

“…Appropriate intestinal epithelial regeneration is required to improve the outcomes of treatment for IBD [ 74 ]. YAP1 regulation is a responsive mechanism for mucosal regeneration in an IBD mouse model induced using dextran sulfate sodium [ 108 , 144 ]. We suggest that the three-part mechanism of nAChR, Hippo, and Notch signaling permits adjustments in the rate of ISCs and their daughter cells to maintain the stem and daughter cell density in the adult mouse over the long term.…”

Section: Iscs In the Adult Gutmentioning

confidence: 99%

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Multiple Roles for Cholinergic Signaling from the Perspective of Stem Cell Function

Takahashi

2021

IJMS

Self Cite

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Stem cells have extensive proliferative potential and the ability to differentiate into one or more mature cell types. The mechanisms by which stem cells accomplish self-renewal provide fundamental insight into the origin and design of multicellular organisms. These pathways allow the repair of damage and extend organismal life beyond that of component cells, and they probably preceded the evolution of complex metazoans. Understanding the true nature of stem cells can only come from discovering how they are regulated. The concept that stem cells are controlled by particular microenvironments, also known as niches, has been widely accepted. Technical advances now allow characterization of the zones that maintain and control stem cell activity in several organs, including the brain, skin, and gut. Cholinergic neurons release acetylcholine (ACh) that mediates chemical transmission via ACh receptors such as nicotinic and muscarinic receptors. Although the cholinergic system is composed of organized nerve cells, the system is also involved in mammalian non-neuronal cells, including stem cells, embryonic stem cells, epithelial cells, and endothelial cells. Thus, cholinergic signaling plays a pivotal role in controlling their behaviors. Studies regarding this signal are beginning to unify our understanding of stem cell regulation at the cellular and molecular levels, and they are expected to advance efforts to control stem cells therapeutically. The present article reviews recent findings about cholinergic signaling that is essential to control stem cell function in a cholinergic niche.

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“…Thus, dedifferentiation and modification of the committed cells into stem/progenitor cells has been observed in ectopic YAP1/TAZ expression [34]. Recent findings have also shown the interaction of other signaling pathways including Wnt, Notch and epidermal growth factor (EGF) with the Hippo pathway and YAP1/TAZ co-activators [32,38]. In this context, it is interesting to note that during intestinal regeneration YAP1 participates in intestinal stem cell maintenance through the temporary suppression of Wnt signaling [36].…”

Section: Introductionmentioning

confidence: 99%

The Hippo Pathway Effector YAP1 Regulates Intestinal Epithelial Cell Differentiation

Fallah

Beaulieu

2020

Cells

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The human intestine is covered by epithelium, which is continuously replaced by new cells provided by stem cells located at the bottom of the glands. The maintenance of intestinal stem cells is supported by a niche which is composed of several signaling proteins including the Hippo pathway effectors YAP1/TAZ. The role of YAP1/TAZ in cell proliferation and regeneration is well documented but their involvement on the differentiation of intestinal epithelial cells is unclear. In the present study, the role of YAP1/TAZ on the differentiation of intestinal epithelial cells was investigated using the HT29 cell line, the only multipotent intestinal cell line available, with a combination of knockdown approaches. The expression of intestinal differentiation cell markers was tested by qPCR, Western blot, indirect immunofluorescence and electron microscopy analyses. The results show that TAZ is not expressed while the abolition of YAP1 expression led to a sharp increase in goblet and absorptive cell differentiation and reduction of some stem cell markers. Further studies using double knockdown experiments revealed that most of these effects resulting from YAP1 abolition are mediated by CDX2, a key intestinal cell transcription factor. In conclusion, our results indicate that YAP1/TAZ negatively regulate the differentiation of intestinal epithelial cells through the inhibition of CDX2 expression.

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Stem Cell Signaling Pathways in the Small Intestine

Cited by 45 publications

References 123 publications

Integrated Analyses of Mouse Stem Cell Transcriptomes Provide Clues for Stem Cell Maintenance and Transdifferentiation

Integrated Analyses of Mouse Stem Cell Transcriptomes Provide Clues for Stem Cell Maintenance and Transdifferentiation

Multiple Roles for Cholinergic Signaling from the Perspective of Stem Cell Function

The Hippo Pathway Effector YAP1 Regulates Intestinal Epithelial Cell Differentiation

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