TrpA1 is a shear stress mechanosensing channel regulating intestinal homeostasis in Drosophila

Adult stem cells are essential for maintaining normal tissue homeostasis and supporting tissue repair. Although genetic and biochemical programs controlling adult stem cell behavior have been extensively investigated, how mechanosensing regulates stem cells and tissue homeostasis is not well understood. Here, we show that shear stress can activate enteroendocrine cells, but not other gut epithelial cell types, to regulate intestine stem cell-mediated gut homeostasis. This shear stress sensing is mediated by transient receptor potential A1 (TrpA1), a Ca2+-permeable ion channel expressed only in enteroendocrine cells among all gut epithelial cells. Genetic depletion of TrpA1 or modification of its shear stress sensing function causes reduced intestine stem cell proliferation and intestine growth. We further show that among the TrpA1 splice variants, only select isoforms are activated by shear stress. Altogether, our results suggest the naturally occurring mechanical force such as fluid passing generated shear stress regulates intestinal stem cell-mediated tissue growth by activating enteroendocrine cells, and Drosophila TrpA1 as a new shear stress sensor.

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Moonlighting α-PheRS connects JAK/STAT with Notch signaling to modulate intestinal homeostasis

10.1101/2019.12.19.882530 ◽

2019 ◽

Author(s):

Manh Tin Ho ◽

Jiongming Lu ◽

Beat Suter

Keyword(s):

Stem Cells ◽

Cell Proliferation ◽

Stem Cell ◽

Notch Signaling ◽

Notch Pathway ◽

Trna Synthetase ◽

Tissue Growth ◽

Tissue Homeostasis ◽

Rnai Phenotype ◽

Stem Cell Proliferation

Summary / AbstractAminoacyl tRNA synthetases (aaRSs) not only load the appropriate amino acid onto their cognate tRNA, many of them perform additional functions that are not necessarily related to their canonical activities. Phenylalanyl tRNA synthetase (PheRS/FARS) levels are elevated in multiple cancers and, interestingly, also in normal stem cells. Our results show that elevated expression of the α-PheRS subunit stimulates cell proliferation in different tissues, while downregulation of α-PheRS reduces organ size. The stimulation of proliferation is independent of the β-PheRS subunit and the aminoacylation activity, and it does not visibly stimulate translation. Furthermore, stem cell-specific overexpression of α-PheRS caused a tumor phenotype in the intestine, a phenotype indistinguishable from the Notch RNAi phenotype in the same cells. Genetic interactions between α-PheRS and Notch suggest that their activities neutralize each other and that elevated α-PheRS levels attenuate Notch signaling whether Notch induces differentiation into enterocytes or neuroblast stem cell proliferation. Indeed, in the wing discs system, elevated α-PheRS levels suppress Notch transcriptional activity. α-PheRS therefore seems to act as a general regulator of Notch signaling, and its own levels are in turn controlled by Stat92E, the transcription factor of the JAK/STAT signaling pathway that is needed for the differentiation of intestinal stem cells during tissue homeostasis under normal conditions. From this we conclude that the α-PheRS subunit can transmit the activity status of the JAK/STAT pathway to the Notch pathway as a mechanism to coordinate stem cell proliferation with differentiation. In this process, α-PheRS levels balance between tissue development and tissue growth to regulate tissue homeostasis.

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Application of Nanomaterials in Regulating the Fate of Adipose-derived Stem Cells

Current Stem Cell Research & Therapy ◽

10.2174/1574888x15666200502000343 ◽

2021 ◽

Vol 16 (1) ◽

pp. 3-13

Author(s):

Lang Wang ◽

Yong Li ◽

Maorui Zhang ◽

Kui Huang ◽

Shuanglin Peng ◽

...

Keyword(s):

Stem Cells ◽

Stem Cell ◽

Stem Cell Research ◽

Adult Stem Cells ◽

Adipose Derived Stem Cells ◽

Proliferation And Differentiation ◽

Recent Developments ◽

Good Biocompatibility ◽

Regulatory Effects ◽

New Treatment

Adipose-derived stem cells are adult stem cells which are easy to obtain and multi-potent. Stem-cell therapy has become a promising new treatment for many diseases, and plays an increasingly important role in the field of tissue repair, regeneration and reconstruction. The physicochemical properties of the extracellular microenvironment contribute to the regulation of the fate of stem cells. Nanomaterials have stable particle size, large specific surface area and good biocompatibility, which has led them being recognized as having broad application prospects in the field of biomedicine. In this paper, we review recent developments of nanomaterials in adipose-derived stem cell research. Taken together, the current literature indicates that nanomaterials can regulate the proliferation and differentiation of adipose-derived stem cells. However, the properties and regulatory effects of nanomaterials can vary widely depending on their composition. This review aims to provide a comprehensive guide for future stem-cell research on the use of nanomaterials.

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Induction of Stem Cell Like Cells from Mouse Embryonic Fibroblast by Short-Term Shear Stress and Vitamin C

Applied Sciences ◽

10.3390/app11041941 ◽

2021 ◽

Vol 11 (4) ◽

pp. 1941

Author(s):

Seungmin Yeom ◽

Myung Chul Lee ◽

Shambhavi Pandey ◽

Jaewoon Lim ◽

Sangbae Park ◽

...

Keyword(s):

Stem Cells ◽

Shear Stress ◽

Stem Cell ◽

Vitamin C ◽

Suspension Culture ◽

Small Molecules ◽

Tumor Development ◽

Embryonic Stem ◽

Short Term ◽

External Stimuli

Induced pluripotent stem cells (iPSCs) are a good medicine source because of their potential to differentiate into various tissues or cells. However, traditionally, iPSCs made by specific transgenes and virus vectors are not appropriate for clinical use because of safety concerns and risk of tumor development. The goal of this research was to develop an alternative method for reprogramming, using small molecules and external stimuli. Two groups were established: short-term shear stress (STSS) under suspension culture and a combination of short-term shear stress and vitamin C (SSVC) under suspension culture. For STSS, the pipetting was carried out for cells twice per day for 2 min for 14 days in the embryonic stem cell (ES) medium. In the case of SSVC, the procedure was the same as for STSS however, its ES medium included 10 µM of vitamin C. After 14 days, all spheroids were picked and checked for pluripotency by ALP (alkaline phosphatase) assay and immunocytochemistry. Both groups partially showed the characteristics of stem cells but data demonstrated that the spheroids under shear stress and vitamin C had improved stem cell-like properties. This research showed the possibility of external stimuli and small molecules to reprogram the somatic cells without the use of transgenes.

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GSK3β, a Master Kinase in the Regulation of Adult Stem Cell Behavior

Cells ◽

10.3390/cells10020225 ◽

2021 ◽

Vol 10 (2) ◽

pp. 225

Author(s):

Claire Racaud-Sultan ◽

Nathalie Vergnolle

Keyword(s):

Stem Cells ◽

Stem Cell ◽

Adult Stem Cells ◽

Glycogen Synthase ◽

Inflammatory Diseases ◽

Adult Stem Cell ◽

Leukemic Cells ◽

Cell Phenotype ◽

Epithelial Regeneration ◽

Cell Functions

In adult stem cells, Glycogen Synthase Kinase 3β (GSK3β) is at the crossroad of signaling pathways controlling survival, proliferation, adhesion and differentiation. The microenvironment plays a key role in the regulation of these cell functions and we have demonstrated that the GSK3β activity is strongly dependent on the engagement of integrins and protease-activated receptors (PARs). Downstream of the integrin α5β1 or PAR2 activation, a molecular complex is organized around the scaffolding proteins RACK1 and β-arrestin-2 respectively, containing the phosphatase PP2A responsible for GSK3β activation. As a consequence, a quiescent stem cell phenotype is established with high capacities to face apoptotic and metabolic stresses. A protective role of GSK3β has been found for hematopoietic and intestinal stem cells. Latters survived to de-adhesion through PAR2 activation, whereas formers were protected from cytotoxicity through α5β1 engagement. However, a prolonged activation of GSK3β promoted a defect in epithelial regeneration and a resistance to chemotherapy of leukemic cells, paving the way to chronic inflammatory diseases and to cancer resurgence, respectively. In both cases, a sexual dimorphism was measured in GSK3β-dependent cellular functions. GSK3β activity is a key marker for inflammatory and cancer diseases allowing adjusted therapy to sex, age and metabolic status of patients.

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Dielectrophoresis: A Review of Applications for Stem Cell Research

Journal of Biomedicine and Biotechnology ◽

10.1155/2010/182581 ◽

2010 ◽

Vol 2010 ◽

pp. 1-7 ◽

Cited By ~ 85

Author(s):

Ronald Pethig ◽

Anoop Menachery ◽

Steve Pells ◽

Paul De Sousa

Keyword(s):

Stem Cells ◽

Stem Cell ◽

Stem Cell Research ◽

Adult Stem Cells ◽

Surface Proteins ◽

Specific Cell ◽

State Changes ◽

Ultimate Fate ◽

Apoptosis And Necrosis ◽

Specific Cell Surface

Dielectrophoresis can discriminate distinct cellular identities in heterogeneous populations, and monitor cell state changes associated with activation and clonal expansion, apoptosis, and necrosis, without the need for biochemical labels. Demonstrated capabilities include the enrichment of haematopoetic stem cells from bone marrow and peripheral blood, and adult stem cells from adipose tissue. Recent research suggests that this technique can predict the ultimate fate of neural stem cells after differentiationbeforethe appearance of specific cell-surface proteins. This review summarises the properties of cells that contribute to their dielectrophoretic behaviour, and their relevance to stem cell research and translational applications.

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Quiescent, Slow-Cycling Stem Cell Populations in Cancer: A Review of the Evidence and Discussion of Significance

Journal of Oncology ◽

10.1155/2011/396076 ◽

2011 ◽

Vol 2011 ◽

pp. 1-11 ◽

Cited By ~ 159

Author(s):

Nathan Moore ◽

Stephen Lyle

Keyword(s):

Cell Cycle ◽

Stem Cells ◽

Stem Cell ◽

Cancer Stem Cells ◽

Adult Stem Cells ◽

Cell Populations ◽

Proliferative Potential ◽

Cell Cycle Regulators ◽

Slow Cycling ◽

Stem Cell Populations

Long-lived cancer stem cells (CSCs) with indefinite proliferative potential have been identified in multiple epithelial cancer types. These cells are likely derived from transformed adult stem cells and are thought to share many characteristics with their parental population, including a quiescent slow-cycling phenotype. Various label-retaining techniques have been used to identify normal slow cycling adult stem cell populations and offer a unique methodology to functionally identify and isolate cancer stem cells. The quiescent nature of CSCs represents an inherent mechanism that at least partially explains chemotherapy resistance and recurrence in posttherapy cancer patients. Isolating and understanding the cell cycle regulatory mechanisms of quiescent cancer cells will be a key component to creation of future therapies that better target CSCs and totally eradicate tumors. Here we review the evidence for quiescent CSC populations and explore potential cell cycle regulators that may serve as future targets for elimination of these cells.

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Article Commentary: Stem Cell Research in Cell Transplantation: An Analysis of Geopolitical Influence by Publications

Cell Transplantation ◽

10.3727/000000007783465190 ◽

2007 ◽

Vol 16 (8) ◽

pp. 867-873 ◽

Cited By ~ 5

Author(s):

David J. Eve ◽

Paul R. Sanberg

Keyword(s):

Stem Cells ◽

Stem Cell ◽

Cell Transplantation ◽

Adult Stem Cells ◽

Adult Stem Cell ◽

Therapeutic Area ◽

Fetal Stem Cells ◽

Major Player ◽

The Us ◽

Restricted Use

One of the fastest growing fields in researching treatments for neurodegenerative and other disorders is the use of stem cells. These cells are naturally occurring and can be obtained from three different stages of an organism's life: embryonic, fetal, and adult. In the US, political doctrine has restricted use of federal funds for stem cells, enhancing research towards an adult source. In order to determine how this legislation may be represented by the stem cell field, a retrospective analysis of stem cell articles published in the journal Cell Transplantation over a 2-year period was performed. Cell Transplantation is considered a translational journal from preclinical to clinical, so it was of interest to determine the publication outcome of stem cell articles 6 years after the US regulations. The distribution of the source of stem cells was found to be biased towards the adult stage, but relatively similar over the embryonic and fetal stages. The fetal stem cell reports were primarily neural in origin, whereas the adult stem cell ones were predominantly mesenchymal and used mainly in neural studies. The majority of stem cell studies published in Cell Transplantation were found to fall under the umbrella of neuroscience research. American scientists published the most articles using stem cells with a bias towards adult stem cells, supporting the effect of the legislation, whereas Europe was the leading continent with a bias towards embryonic and fetal stem cells, where research is “controlled” but not restricted. Japan was also a major player in the use of stem cells. Allogeneic transplants (where donor and recipient are the same species) were the most common transplants recorded, although the transplantation of human-derived stem cells into rodents was the most common specific transplantation performed. This demonstrates that the use of stem cells is an increasingly important field (with a doubling of papers between 2005 and 2006), which is likely to develop into a major therapeutic area over the next few decades and that funding restrictions can affect the type of research being performed.

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Antioxidant Effects of Caffeic Acid Lead to Protection of Drosophila Intestinal Stem Cell Aging

Frontiers in Cell and Developmental Biology ◽

10.3389/fcell.2021.735483 ◽

2021 ◽

Vol 9 ◽

Author(s):

Xiao Sheng ◽

Yuedan Zhu ◽

Juanyu Zhou ◽

La Yan ◽

Gang Du ◽

...

Keyword(s):

Stem Cells ◽

Stem Cell ◽

Caffeic Acid ◽

Stress Responses ◽

Adult Stem Cells ◽

Cell Function ◽

Cell Aging ◽

Positive Effects ◽

Age Related ◽

Tissue Aging

The dysfunction or exhaustion of adult stem cells during aging is closely linked to tissue aging and age-related diseases. Circumventing this aging-related exhaustion of adult stem cells could significantly alleviate the functional decline of organs. Therefore, identifying small molecular compounds that could prevent the age-related decline of stem cell function is a primary goal in anti-aging research. Caffeic acid (CA), a phenolic compound synthesized in plants, offers substantial health benefits for multiple age-related diseases and aging. However, the effects of CA on adult stem cells remain largely unknown. Using the Drosophila midgut as a model, this study showed that oral administration with CA significantly delayed age-associated Drosophila gut dysplasia caused by the dysregulation of intestinal stem cells (ISCs) upon aging. Moreover, administering CA retarded the decline of intestinal functions in aged Drosophila and prevented hyperproliferation of age-associated ISC by suppressing oxidative stress-associated JNK signaling. On the other hand, CA supplementation significantly ameliorated the gut hyperplasia defect and reduced environmentally induced mortality, revealing the positive effects of CA on tolerance to stress responses. Taken together, our findings report a crucial role of CA in delaying age-related changes in ISCs of Drosophila.

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