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.

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 Mammalian Homeobox B6 Expression Can Be Correlated With Erythropoietin Production Sites and Erythropoiesis During Development, But Not With Hematopoietic or Nonhematopoietic Stem Cell Populations

Blood ◽  
1997 ◽  
Vol 89 (8) ◽  
pp. 2723-2735 ◽  
Author(s):  
Frank Zimmermann ◽  
Ivan N. Rich
Keyword(s):  
Gene Expression ◽  
Stem Cell ◽  
Hox Genes ◽  
Fetal Liver ◽  
Single Gene ◽  
Lymphoid Cells ◽  
Cell Populations ◽  
Hematopoietic Stem ◽  
Hox Gene ◽  
Stem Cell Populations

Abstract There has been increasing interest in the involvement of mammalian homeobox (HOX) genes in hematopoietic regulation. The HOX genes are clustered in 4 chromosomes in mice and humans. In general, 5′ end HOX gene expression is predominant in hematopoietic stem cell populations, whereas 3′ end HOX gene expression are primarily found in committed progenitor cells. Furthermore, HOX genes of the A cluster are generally found in myelomonocytic cells, B cluster genes in erythropoietic cells, and C cluster genes in lymphoid cells. The results presented here concentrate on a single gene, namely HOX B6. Preliminary observations using whole mount in situ hybridization showed that both HOX B6 and erythropoietin (EPO) gene expression occurred in exactly the same areas of the 8.5-day mouse embryo. As a consequence, we studied the expression of HOX B6 and EPO gene expression from 6.5 to 19.5 days of gestation, in the neonate, and in the adult. It was found that the sequential transfer of erythropoiesis in different organs during development was followed by a similar transfer of HOX B6 and EPO gene expression. Between days 16.5 and 17.5, both HOX B6 and EPO gene expression decrease in the fetal liver, even though hepatic erythropoiesis continues to decline and is transferred to the fetal spleen. Precisely at this time point, HOX B6 and EPO gene expression are transferred to both the fetal spleen and fetal kidney. However, surprisingly, expression of both genes increases again in the fetal liver just before birth. HOX B6 is expressed in cells from in vitro erythropoietic colonies (colony-forming unit-erythroid and burst-forming unit-erythroid) and TER-119+ erythroid cells but not in hematopoietic or nonhematopoietic stem cell populations. When the latter two populations are allowed to differentiate into erythropoietic cells, HOX B6 and erythroid-relevant markers are expressed. The results indicate that HOX B6 is intimately involved in the regulation of the erythropoietic system and could be a marker for this lineage.

scholarly journals CD146/MCAM defines functionality of human bone marrow stromal stem cell populations

2016 ◽  
Vol 7 (1) ◽  
Author(s):  
Linda Harkness ◽  
Walid Zaher ◽  
Nicholas Ditzel ◽  
Adiba Isa ◽  
Moustapha Kassem
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
Human Bone ◽  
Human Bone Marrow ◽  
Cell Populations ◽  
Stromal Stem Cell ◽  
Stem Cell Populations

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.

Abstract LB-102: Role of HOX genes in regulation of stem cell populations in normal and malignant colon tissue

2012 ◽  
Author(s):  
Seema Bhatlekar ◽  
Kirk Czymmek ◽  
Vignesh Viswanathan ◽  
Greg Gonye ◽  
Bruce Boman
Keyword(s):  
Stem Cell ◽  
Hox Genes ◽  
Cell Populations ◽  
Colon Tissue ◽  
Stem Cell Populations

scholarly journals Genotype-restricted growth and aging patterns in hematopoietic stem cell populations of allophenic mice.

1990 ◽  
Vol 171 (5) ◽  
pp. 1547-1565 ◽  
Author(s):  
G Van Zant ◽  
B P Holland ◽  
P W Eldridge ◽  
J J Chen
Keyword(s):  
Stem Cells ◽  
Cell Proliferation ◽  
Stem Cell ◽  
Blood Cell ◽  
Cell Population ◽  
Stromal Cell ◽  
Stem Cell Population ◽  
Cell Populations ◽  
Stem Cell Proliferation ◽  
Stem Cell Populations

We have studied contributions to hematopoiesis of genetically distinct stem cell populations in allophenic mice. Chimeras were made by aggregating embryos of inbred strains known to differ with respect to stem cell population kinetics. One partner strain (DBA/2) has previously been shown to normally have a stem cell (CFU-S) population of which 24% are in S-phase of the cell cycle, whereas the homologous population of the other partner strain (C57BL/6) was characterized by having only 2.6% in cycle (7). Contributions of the chimeric stem cell population to mature blood cell pools were studied throughout the life of the mice and intrinsic differences in stem cell function and aging were reflected in dynamic patterns of blood cell composition. The DBA/2 stem cell population was eclipsed by stem cells of the C57BL/6 genotype and, after 1.5-3 yr, the hemato-lymphoid composition of 22 of 27 mice studied for this long had shifted by at least 25 percentage points toward the C57BL/6 genotype. 8 of the 27 had hematolymphoid populations solely of C57BL/6 origin. To test whether or not a population of stem cells with an inherently higher cycling rate (DBA/2) might have a competitive advantage during repopulation, we engrafted allophenic marrow into lethally irradiated (C57BL/6 x DBA/2)F1 recipients. DBA/2 hematopoiesis was predominant early, far outstripping its representation in the marrow graft. Perhaps as a consequence of inherently greater DBA/2 stem cell proliferation, the populations of developmentally more restricted precursor populations (CFU-E, BFU-E, CFU-GM, CFU-GEMM) showed an overwhelming DBA/2 bias in the first 2-3 mo after engraftment. However, as in the allophenic mice themselves during the aging process, the C57BL/6 genotypic representation was ascendant over the subsequent months. The shift toward C57BL/6 genotype was first documented in the marrow and spleen precursor cell populations and was subsequently reflected in the circulating, mature blood cells. Bone marrow-derived stromal cell cultures from engrafted mice were studied and genotypic analyses showed donor representation in stromal cell populations that reflected donor hematopoietic contributions in the same recipient. Results from these studies involving two in vivo settings (allophenic mice and engraftment by allophenic marrow) are consistent with the notion that a cell autonomous difference in stem cell proliferation confers on one population a competitive repopulating advantage, but at the expense of longevity.

scholarly journals Heterogeneity and ‘memory’ in stem cell populations

2020 ◽  
Author(s):  
Patrick S. Stumpf ◽  
Fumio Arai ◽  
Ben D. MacArthur
Keyword(s):  
Stem Cell ◽  
Stem Cell Population ◽  
Cell Populations ◽  
Cell Numbers ◽  
Stem Cell Proliferation ◽  
Pure Cell ◽  
Age Structured ◽  
Stem Cell Populations ◽  
Age Structured Model ◽  
Population Function

ABSTRACTModern single cell experiments have revealed unexpected heterogeneity in apparently functionally ‘pure’ cell populations. However, we are still lacking a conceptual framework to understand this heterogeneity. Here, we propose that cellular memories – the ability of individual cells to record their developmental past and adapt their response to their environment accordingly – are an essential ingredient in any such theory. We illustrate this idea by considering a simple age-structured model of stem cell proliferation. Using this model we argue that heterogeneity is central to stem cell population function, and memories naturally explain why stem cell numbers increase through life, yet regenerative potency simultaneously declines.

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