scholarly journals Mitochondria deliver a gut check to intestinal stem cells

2017 ◽  
Vol 216 (8) ◽  
pp. 2231-2231
Author(s):  
Ben Short
Keyword(s):  
Stem Cells ◽  
Cell Proliferation ◽  
Stem Cell ◽  
Tissue Homeostasis ◽  
Intestinal Stem Cells ◽  
Stem Cell Proliferation ◽  
Mitochondrial Turnover

Mitochondrial turnover regulates stem cell proliferation and tissue homeostasis in Drosophila intestines.

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

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.

scholarly journals Mitochondria regulate intestinal stem cell proliferation and epithelial homeostasis through FOXO

2020 ◽  
Vol 31 (14) ◽  
pp. 1538-1549
Author(s):  
Fan Zhang ◽  
Mehdi Pirooznia ◽  
Hong Xu
Keyword(s):  
Stem Cells ◽  
Cell Proliferation ◽  
Transcription Factor ◽  
Stem Cell ◽  
Electron Transport Chain ◽  
Intestinal Stem Cell ◽  
Stem Cell Proliferation ◽  
Epithelial Homeostasis ◽  
Chain Complexes ◽  
Transport Chain

Deficiencies in electron transport chain complexes increase the activity of FOXO transcription factor in Drosophila midgut stem cells, which impairs stem cell proliferation and enterocyte specification.

EVALUATION OF HERBAL EXTRACTS SYNERGISTIC ACTIVITY USING TISSUE STEM CELLS

INDIAN DRUGS ◽  
2017 ◽  
Vol 54 (02) ◽  
pp. 73-75
Author(s):  
S. Priya ◽  
Keyword(s):  
Stem Cells ◽  
Cell Proliferation ◽  
Stem Cell ◽  
System Analysis ◽  
Cultured Cells ◽  
Well Being ◽  
Ocimum Sanctum ◽  
Synergistic Activity ◽  
Stem Cell Proliferation ◽  
Cell Proliferation And Differentiation

Herbal stem cell therapy promotes endogenous stem cell proliferation and differentiation and is ued in the treatment of various human diseases. At present, recommendations are warranted to support the consumption of foods rich in bioactive components. Stem cells and progenitor cells from organs form the basis for well-being of the mammalian system. Analysis based on these cultured cells would form a viable alternative to stem cell transplantation, and would facilitate to design approaches that stimulate endogenous stem cells through diet to promote healing and regeneration. In the present study, synergistic activity of selected herbs such as Phyllanthus amarus, Myristica fragrans, Ocimum sanctum and Withania somnifera were analysed for their stem cell proliferation enhancing activity using goat bone marrow derived stem cells.

scholarly journals Unveiling role of sphingosine-1-phosphate receptor 2 as a brake of epithelial stem cell proliferation and a tumor suppressor in colorectal cancer

2020 ◽  
Vol 39 (1) ◽  
Author(s):  
Luciana Petti ◽  
Giulia Rizzo ◽  
Federica Rubbino ◽  
Sudharshan Elangovan ◽  
Piergiuseppe Colombo ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Stem Cells ◽  
Cell Proliferation ◽  
Stem Cell ◽  
Tumor Suppressor ◽  
Normal Mucosa ◽  
Intestinal Stem Cells ◽  
Intestinal Epithelial ◽  
Sphingosine 1 Phosphate

Abstract Background Sphingosine-1-phosphate receptor 2 (S1PR2) mediates pleiotropic functions encompassing cell proliferation, survival, and migration, which become collectively de-regulated in cancer. Information on whether S1PR2 participates in colorectal carcinogenesis/cancer is scanty, and we set out to fill the gap. Methods We screened expression changes of S1PR2 in human CRC and matched normal mucosa specimens [N = 76]. We compared CRC arising in inflammation-driven and genetically engineered models in wild-type (S1PR2+/+) and S1PR2 deficient (S1PR2−/−) mice. We reconstituted S1PR2 expression in RKO cells and assessed their growth in xenografts. Functionally, we mimicked the ablation of S1PR2 in normal mucosa by treating S1PR2+/+ organoids with JTE013 and characterized intestinal epithelial stem cells isolated from S1PR2−/−Lgr5-EGFP- mice. Results S1PR2 expression was lost in 33% of CRC; in 55%, it was significantly decreased, only 12% retaining expression comparable to normal mucosa. Both colitis-induced and genetic Apc+/min mouse models of CRC showed a higher incidence in size and number of carcinomas and/or high-grade adenomas, with increased cell proliferation in S1PR2−/− mice compared to S1PR2+/+ controls. Loss of S1PR2 impaired mucosal regeneration, ultimately promoting the expansion of intestinal stem cells. Whereas its overexpression attenuated cell cycle progression, it reduced the phosphorylation of AKT and augmented the levels of PTEN. Conclusions In normal colonic crypts, S1PR2 gains expression along with intestinal epithelial cells differentiation, but not in intestinal stem cells, and contrasts intestinal tumorigenesis by promoting epithelial differentiation, preventing the expansion of stem cells and braking their malignant transformation. Targeting of S1PR2 may be of therapeutic benefit for CRC expressing high Lgr5. Graphical Abstract. Schematic drawing of the role of S1PR2 in normal mucosa and colorectal cancer. In the normal mucosa, S1PR2 is highly expressed by differentiated cells at the upper region of both colon and intestinal crypts (S1PR2 ON), but not by the undifferentiated stem cell at the base of the crypts (S1PR2 OFF), in which acts as a negative proliferative regulator promoting epithelial differentiation. Its loss leads to the expansion of stem cells and reduced levels of PTEN and Axin-2, two negative regulators respectively of PI3K/AKT and Wnt signaling that control β-catenin signaling. The translocation of β-catenin into the nucleus promotes the transcription of target genes involved in the proliferation and malignant transformation. Thereby, S1PR2 works in the intestine as a tumor suppressor

scholarly journals Microfluidic Enrichment of Mouse Epidermal Stem Cells and Validation of Stem Cell Proliferation In Vitro

2013 ◽  
Vol 19 (10) ◽  
pp. 765-773 ◽  
Author(s):  
Beili Zhu ◽  
James Smith ◽  
Martin L. Yarmush ◽  
Yaakov Nahmias ◽  
Brian J. Kirby ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cell Proliferation ◽  
Stem Cell ◽  
Epidermal Stem Cells ◽  
Stem Cell Proliferation ◽  
Proliferation In Vitro

Excessive Hematopoietic Stem Cell Proliferation Leads to Chromosomal Instability

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4772-4772
Author(s):  
Liliana Souza ◽  
Natalyn Hawk ◽  
Sweta Sengupta ◽  
Carlos Cabrera ◽  
Morgan L. McLemore
Keyword(s):  
Cell Cycle ◽  
Stem Cells ◽  
Cell Proliferation ◽  
Stem Cell ◽  
Chromosomal Instability ◽  
Wild Type ◽  
Dna Breaks ◽  
Hematopoietic Stem ◽  
Stem Cell Proliferation ◽  
Double Stranded Dna

Abstract Truncation mutations in the granulocyte colony stimulating factor receptor (G-CSFR), common in severe congenital neutropenia (SCN), lead to excessive stem cell proliferation in response to G-CSF. These G-CSFR mutants are (at least indirectly) implicated in the progression of these patients to acute leukemia. Since SCN patients require continuous G-CSF treatment throughout their lifespan, we hypothesize that excessive stem cell proliferation can lead to DNA damage. Stem cells are relatively quiescent and rarely enter the cell cycle under normal conditions. During the cell cycle cells generate approximately 5000 single strand DNA lesions per nucleus (Vilenchik and Knudson, 2003). Approximately 1% of these lesions are ultimately converted to double strand DNA breaks (DSBs). Hematopoietic stem cells are found within the Sca+ ckit+ Lin- (KLS) population. Wild type and mice bearing a mutant G-CSFR similar to that found in patients with SCN were treated with G-CSF. After 21 days of treatment with G-CSF (10 ug/kg/day), the KLS population in the bone marrow increased four-fold in wild type mice and eight-fold in mutant mice. We isolated Lin-Sca+ bone marrow cells from these G-CSF treated mice and evaluated for the presence of double stranded DNA breaks by staining with anti-phospho-H2AX by immunofluorescence. H2AX is a histone whose phosphorylated form localizes to the site of double stranded DNA breaks. The results showed that there is an 8-fold increase in the DSB in wild type Lin-Sca+ and 10-fold in mutant Lin-Sca+ when compared to cells from untreated mice. This data suggests that excessive proliferation can contribute to an increase in DSBs in hematopoietic stem cells. Investigation of potential mechanisms contributing to DSB formation are ongoing. Understanding the causes and trends of chromosomal instability would improve our understanding of leukemogenesis and potentially reveal novel treatment strategies.

scholarly journals Interleukin-3-stimulated haemopoietic stem cell proliferation. Evidence for activation of protein kinase C and Na+/H+ exchange without inositol lipid hydrolysis

1988 ◽  
Vol 256 (2) ◽  
pp. 585-592 ◽  
Author(s):  
A D Whetton ◽  
S J Vallance ◽  
P N Monk ◽  
E J Cragoe ◽  
T M Dexter ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cell Proliferation ◽  
Stem Cell ◽  
Protein Kinase C ◽  
Protein Kinase ◽  
Intracellular Ph ◽  
Stem Cell Proliferation ◽  
Interleukin 3 ◽  
Haemopoietic Stem Cell ◽  
Kinase C

Interleukin 3 (IL-3) is an important regulator of haemopoietic stem cell proliferation both in vivo and in vitro. Little is known about the possible mechanisms whereby this growth factor acts on stem cells to stimulate cell survival and proliferation. Here we have investigated the role of intracellular pH and the Na+/H+ antiport in stem cell proliferation using the multipotential IL-3-dependent stem cell line, FDCP-Mix 1. Evidence is presented that IL-3 can stimulate the activation of an amiloride-sensitive Na+/H+ exchange via protein kinase C activation. IL-3-mediated activation of the Na+/H+ exchange is not observed in FDCP-Mix 1 cells where protein kinase C levels have been down-modulated by treatment with phorbol esters. Also the protein kinase C inhibitor H7 can inhibit IL-3-mediated increases in intracellular pH. This activation of Na+/H+ exchange via protein kinase C has been shown to occur with no measurable effects of IL-3 on inositol lipid hydrolysis or on cytosolic Ca2+ levels. Evidence is also presented that this IL-3-stimulated alkalinization acts as a signal for cellular proliferation in stem cells.

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