scholarly journals The Implications of Small Stem Cell Niche Sizes and the Distribution of Fitness Effects of New Mutations in Aging and Tumorigenesis

2015 ◽  
Author(s):  
Vincent L. Cannataro ◽  
Scott A. McKinley ◽  
Colette M. St. Mary
Keyword(s):  
Stem Cell ◽  
Stem Cell Niche ◽  
Simulation Analysis ◽  
Somatic Tissue ◽  
Stem Cell Population ◽  
Cell Populations ◽  
Regulatory Regime ◽  
Fitness Effects ◽  
Cell Niche ◽  
Stem Cell Populations

Somatic tissue evolves over a vertebrate's lifetime due to the accumulation of mutations in stem cell populations. Mutations may alter cellular fitness and contribute to tumorigenesis or aging. The distribution of mutational effects within somatic cells is not known. Given the unique regulatory regime of somatic cell division we hypothesize that mutational effects in somatic tissue fall into a different framework than whole organisms; one in which there are more mutations of large effect. Through simulation analysis we investigate the fit of tumor incidence curves generated using exponential and power law Distributions of Fitness Effects (DFE) to known tumorigenesis incidence. Modeling considerations include the architecture of stem cell populations, i.e., a large number of very small populations, and mutations that do and do not fix neutrally in the stem cell niche. We find that the typically quantified DFE in whole organisms is sufficient to explain tumorigenesis incidence. Further, due to the effects of small stem cell population sizes, i.e., strong genetic drift, deleterious mutations are predicted to accumulate, resulting in reduced tissue maintenance. Thus, despite there being a large number of stem cells throughout the intestine, its compartmental architecture leads to significant aging, a prime example of Muller's Ratchet.

scholarly journals The Adipose-derived Stem Cell: Looking Back and Looking Ahead

2010 ◽  
Vol 21 (11) ◽  
pp. 1783-1787 ◽  
Author(s):  
Patricia A. Zuk
Keyword(s):  
Stem Cell ◽  
Historical Perspective ◽  
Es Cells ◽  
Adult Stem Cell ◽  
Stem Cell Population ◽  
Cell Populations ◽  
Stem Cell Populations ◽  
New Applications ◽  
Adipose Derived Stem Cell ◽  
Looking Back

In 2002, researchers at UCLA published a manuscript in Molecular Biology of the Cell describing a novel adult stem cell population isolated from adipose tissue—the adipose-derived stem cell (ASC). Since that time, the ASC has gone on to be one of the most popular adult stem cell populations currently being used in the stem cell field. With multilineage mesodermal potential and possible ectodermal and endodermal potentials also, the ASC could conceivably be an alternate to pluripotent ES cells in both the lab and in the clinic. In this retrospective article, a historical perspective on the ASC is given together with exciting new applications for the stem cell being considered today.

scholarly journals Cellular and molecular characterization of the role of the flk-2/flt-3 receptor tyrosine kinase in hematopoietic stem cells

Blood ◽  
1994 ◽  
Vol 84 (8) ◽  
pp. 2422-2430 ◽  
Author(s):  
FC Zeigler ◽  
BD Bennett ◽  
CT Jordan ◽  
SD Spencer ◽  
S Baumhueter ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Tyrosine Kinase ◽  
Hematopoietic Stem Cell ◽  
Receptor Tyrosine Kinase ◽  
Lymphoid Cells ◽  
Stem Cell Population ◽  
Cell Populations ◽  
Hematopoietic Stem ◽  
Stem Cell Populations

The flk-2/flt-3 receptor tyrosine kinase was cloned from a hematopoietic stem cell population and is considered to play a potential role in the developmental fate of the stem cell. Using antibodies derived against the extracellular domain of the receptor, we show that stem cells from both murine fetal liver and bone marrow can express flk-2/flt-3. However, in both these tissues, there are stem cell populations that do not express the receptor. Cell cycle analysis shows that stem cells that do not express the receptor have a greater percentage of the population in G0 when compared with the flk-2/flt-3- positive population. Development of agonist antibodies to the receptor shows a proliferative role for the receptor in stem cell populations. Stimulation with an agonist antibody gives rise to an expansion of both myeloid and lymphoid cells and this effect is enhanced by the addition of kit ligand. These studies serve to further illustrate the importance of the flk-2/flt-3 receptor in the regulation of the hematopoietic stem cell.

scholarly journals The maize root stem cell niche: a partnership between two sister cell populations

Planta ◽  
2009 ◽  
Vol 231 (2) ◽  
pp. 411-424 ◽  
Author(s):  
Keni Jiang ◽  
Tong Zhu ◽  
Zhaoyan Diao ◽  
Haiyan Huang ◽  
Lewis J. Feldman
Keyword(s):  
Stem Cell ◽  
Stem Cell Niche ◽  
Maize Root ◽  
Cell Populations ◽  
Sister Cell ◽  
Root Stem Cell ◽  
Cell Niche

scholarly journals Cancer treatment in childhood and testicular function: the importance of the somatic environment

2018 ◽  
Vol 7 (2) ◽  
pp. R69-R87 ◽  
Author(s):  
Jan-Bernd Stukenborg ◽  
Kirsi Jahnukainen ◽  
Marsida Hutka ◽  
Rod T Mitchell
Keyword(s):  
Stem Cell ◽  
Cancer Treatment ◽  
Somatic Cell ◽  
Stem Cell Niche ◽  
Subsequent Development ◽  
Experimental Models ◽  
Cell Populations ◽  
Testicular Function ◽  
Future Fertility ◽  
Cell Niche

Testicular function and future fertility may be affected by cancer treatment during childhood. Whilst survival of the germ (stem) cells is critical for ensuring the potential for fertility in these patients, the somatic cell populations also play a crucial role in providing a suitable environment to support germ cell maintenance and subsequent development. Regulation of the spermatogonial germ-stem cell niche involves many signalling pathways with hormonal influence from the hypothalamo-pituitary-gonadal axis. In this review, we describe the somatic cell populations that comprise the testicular germ-stem cell niche in humans and how they may be affected by cancer treatment during childhood. We also discuss the experimental models that may be utilized to manipulate the somatic environment and report the results of studies that investigate the potential role of somatic cells in the protection of the germ cells in the testis from cancer treatment.

scholarly journals Self-Renewal, Multipotency, and the Existence of Two Cell Populations within an Epithelial Stem Cell Niche

Cell ◽  
2004 ◽  
Vol 118 (5) ◽  
pp. 635-648 ◽  
Author(s):  
Cedric Blanpain ◽  
William E. Lowry ◽  
Andrea Geoghegan ◽  
Lisa Polak ◽  
Elaine Fuchs
Keyword(s):  
Stem Cell ◽  
Stem Cell Niche ◽  
Cell Populations ◽  
Self Renewal ◽  
Epithelial Stem Cell ◽  
Cell Niche

scholarly journals Musashi regulates follicle stem cell maintenance and epithelial niche homeostasis in the Drosophila ovary

2020 ◽  
Author(s):  
Nicole A. Siddall ◽  
Franca Casagranda ◽  
Nicole Dominado ◽  
James Heaney ◽  
Jessie M. Sutherland ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Niche ◽  
Wnt Pathway ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Stem Cell Population ◽  
Stem Cell Maintenance ◽  
Lineage Differentiation ◽  
Cell Niche ◽  
Drosophila Ovary

AbstractThe Musashi (Msi) family of RNA-binding proteins regulate maintenance and differentiation of stem cells in multiple tissues of different species. Here, we use the powerful system of the Drosophila ovary to uncover an intrinsic requirement for Msi in both the maintenance of the follicle stem cell population and regulation of the architecture of the follicle stem cell niche. Further, we demonstrate an associated G2 lag of cycling somatic cells within the niche when Msi function is abrogated. Additionally, we show that Msi interaction with the Wnt pathway influences differentiation of anterior germarial escort cells from cells within the follicle stem cell niche region. This provides further evidence that escort cells can be derived from follicle stem/precursor cells and that Msi regulates lineage differentiation of follicle stem cell daughters.

G-CSF Potently Suppresses Osteoblast Activity in the Bone Marrow.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 591-591
Author(s):  
Matthew J. Christopher ◽  
Fulu Liu ◽  
Brenton Short ◽  
Paul J. Simmons ◽  
Ingrid Winkler ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
Stem Cell Niche ◽  
Hematopoietic Progenitor Cell ◽  
Cell Populations ◽  
Rt Pcr ◽  
Hematopoietic Progenitor ◽  
Double Labeling ◽  
Osteoblast Activity ◽  
Cell Niche

Abstract There is accumulating evidence that interaction of stromal cell derived factor-1 (SDF-1/CXCL12) with its cognate receptor, CXCR4, generates signals that regulate hematopoietic progenitor cell (HPC) trafficking in the bone marrow. During G-CSF induced HPC mobilization, SDF-1 protein expression in the bone marrow decreases, thereby attenuating CXCR4 signaling. We recently reported that G-CSF treatment induced a decrease in bone marrow SDF-1 mRNA that closely mirrored the fall in SDF-1 protein, suggesting that G-CSF targets one or more SDF-1 producing cell population in the bone marrow. However, the identity of cell populations in the bone marrow that express SDF-1 is controversial. In the present study, we address this issue by sorting cells into mature hematopoietic, hematopoietic progenitor, endothelial, and osteoblast cell populations. Real time RT-PCR analyses showed that osteoblasts and to a lesser degree endothelial cells are the major sources of SDF-1 production in the bone marrow. Surprisingly, on a per cell basis, SDF-1 expression per osteoblast was only modestly (less than two-fold) reduced in mice treated with G-CSF. These data raised the possibility that, rather than affecting SDF-1 expression per osteoblast, G-CSF regulated the number of osteoblasts in the bone marrow. To explore this possibility, osteoblast number in the bone marrow was measured by histomorphometry. Indeed, after 5 days of G-CSF treatment, a significant reduction in the number of endosteal osteoblasts was observed [number of osteoblasts per mm bone perimeter ± SEM: 74.8 ± 13.5 (untreated) versus 33.3 ± 3.8 (G-CSF)]. Moreover, expression of osteocalcin (a specific marker of mature osteoblasts) in the bone marrow was sharply reduced during G-CSF treatment: a 47 ± 12 fold reduction in osteocalcin mRNA (relative to b-actin mRNA) was observed in the bone marrow of G-CSF-treated mice compared with untreated mice. Finally, calcein double-labeling experiments showed that the mineral apposition rate was significantly reduced in G-CSF-treated mice. However, RT-PCR analyses showed that the G-CSF receptor is not expressed on osteoblasts. Accordingly, G-CSF had no direct effect on osteoblast activity in vitro. Collectively, these data show that G-CSF potently suppresses osteoblast number/activity in the bone marrow through an indirect mechanism. Since osteoblasts are thought to play a key role in establishing and maintaining the stem cell niche in the bone marrow, these data raise the possibility that G-CSF, by regulating osteoblast function (including SDF-1 expression), may have profound effects on the stem cell niche that ultimately contribute to HPC mobilization.

Role of c-mpl in Early Hematopoiesis

Blood ◽  
1998 ◽  
Vol 92 (1) ◽  
pp. 4-10 ◽  
Author(s):  
Gregg P. Solar ◽  
William G. Kerr ◽  
Francis C. Zeigler ◽  
Darren Hess ◽  
Christopher Donahue ◽  
...  
Keyword(s):  
Stem Cell ◽  
Fetal Liver ◽  
Cell Activity ◽  
Physiological Role ◽  
Human Bone ◽  
Stem Cell Population ◽  
Cell Populations ◽  
Human Cd34 ◽  
Stem Cell Populations

Recently, several lines of evidence have indicated an expanded role for thrombopoietin (TPO) and its receptor, c-mpl, in hematopoiesis. In addition to being the primary physiological regulator of platelet production, it is now apparent that TPO also acts during early hematopoiesis. To futher define the role of TPO in early hematopoiesis we have identified discrete murine and human stem cell populations with respect to c-mpl expression and evaluated their potential for hematopoietic engraftment. Fluorescence-activated cell sorter analysis of enriched stem cell populations showed the presence of c-mpl expressing subpopulations. Approximately 50% of the murine fetal liver stem cell–enriched population, AA4+Sca+c-kit+, expressed c-mpl. Analysis of the murine marrow stem cell population LinloSca+c-kit+ showed that 70% of this population expressed c-mpl. Expression of c-mpl was also detected within the human bone marrow CD34+CD38− stem cell progenitor pool and approximately 70% of that population expressed c-mpl. To rigorously evaluate the role of TPO/c-mpl in early hematopoiesis we compared the repopulation capacity of murine stem cell populations with respect to c-mpl expression in a competitive repopulation assay. When comparing the fetal liver progenitor populations, AA4+Sca+c-kit+c-mpl+and AA4+Sca+c-kit+c-mpl−, we found that stem cell activity segregates with c-mpl expression. This result is complemented by the observation that the LinloSca+ population of c-mplgene-deficient mice was sevenfold less potent than LinloSca+ cells from wild-type mice in repopulating activity. The engraftment potential of the human CD34+CD38−c-mpl+ population was evaluated in a severe combined immunodeficient-human bone model. In comparison to the CD34+CD38−c-mpl− population, the CD34+CD38−c-mpl+ cells showed significantly better engraftment. These results demonstrate a physiological role for TPO and its receptor, c-mpl, in regulating early hematopoiesis.

Sign in / Sign up

Export Citation Format

Share Document