scholarly journals A matrix metalloproteinase mediates long-distance attenuation of stem cell proliferation

2014 ◽  
Vol 206 (7) ◽  
pp. 923-936 ◽  
Author(s):  
Xiaoxi Wang ◽  
Andrea Page-McCaw
Keyword(s):  
Stem Cells ◽  
Cell Proliferation ◽  
Stem Cell ◽  
Long Range ◽  
Wing Disc ◽  
Negative Regulator ◽  
Long Distance ◽  
Spatial Control ◽  
Stem Cell Proliferation ◽  
Follicle Stem Cells

Ligand-based signaling can potentiate communication between neighboring cells and between cells separated by large distances. In the Drosophila melanogaster ovary, Wingless (Wg) promotes proliferation of follicle stem cells located ∼50 µm or five cell diameters away from the Wg source. How Wg traverses this distance is unclear. We find that this long-range signaling requires Division abnormally delayed (Dally)-like (Dlp), a glypican known to extend the range of Wg ligand in the wing disc by binding Wg. Dlp-mediated spreading of Wg to follicle stem cells is opposed by the extracellular protease Mmp2, which cleaved Dlp in cell culture, triggering its relocalization such that Dlp no longer contacted Wg protein. Mmp2-deficient ovaries displayed increased Wg distribution, activity, and stem cell proliferation. Mmp2 protein is expressed in the same cells that produce Wg; thus, niche cells produce both a long-range stem cell proliferation factor and a negative regulator of its spreading. This system could allow for spatial control of Wg signaling to targets at different distances from the source.

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.

scholarly journals Extracellular spreading of Wingless is required for Drosophila oogenesis

PLoS Genetics ◽  
2021 ◽  
Vol 17 (4) ◽  
pp. e1009469
Author(s):  
Xiaoxi Wang ◽  
Kimberly S. LaFever ◽  
Indrayani Waghmare ◽  
Andrea Page-McCaw
Keyword(s):  
Stem Cells ◽  
Wnt Signaling ◽  
Long Range ◽  
Wing Disc ◽  
Secreted Protein ◽  
Loss Of Function ◽  
Drosophila Oogenesis ◽  
Central Source ◽  
Follicle Stem Cells

Recent studies have investigated whether the Wnt family of extracellular ligands can signal at long range, spreading from their source and acting as morphogens, or whether they signal only in a juxtacrine manner to neighboring cells. The original evidence for long-range Wnt signaling arose from studies of Wg, a Drosophila Wnt protein, which patterns the wing disc over several cell diameters from a central source of Wg ligand. However, the requirement of long-range Wg for patterning was called into question when it was reported that replacing the secreted protein Wg with a membrane-tethered version, NRT-Wg, results in flies with normally patterned wings. We and others previously reported that Wg spreads in the ovary about 50 μm or 5 cell diameters, from the cap cells to the follicle stem cells (FSCs) and that Wg stimulates FSC proliferation. We used the NRT-wg flies to analyze the consequence of tethering Wg to the cap cells. NRT-wg homozygous flies are sickly, but we found that hemizygous NRT-wg/null flies, carrying only one copy of tethered Wingless, were significantly healthier. Despite their overall improved health, these hemizygous flies displayed dramatic reductions in fertility and in FSC proliferation. Further, FSC proliferation was nearly undetectable when the wg locus was converted to NRT-wg only in adults, and the resulting germarium phenotype was consistent with a previously reported wg loss-of-function phenotype. We conclude that Wg protein spreads from its source cells in the germarium to promote FSC proliferation.

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 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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