Signaling via Smad2 and Smad3 is dispensable for adult murine hematopoietic stem cell function in vivo

2017 ◽  
Vol 55 ◽  
pp. 34-44.e2 ◽  
Author(s):  
Matilda Billing ◽  
Emma Rörby ◽  
Maria Dahl ◽  
Ulrika Blank ◽  
Silja Andradottír ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell ◽  
Cell Function ◽  
Hematopoietic Stem ◽  
Murine Hematopoietic Stem Cell

Loss of FancC Function Results in Decreased Hematopoietic Stem Cell Repopulating Ability

Blood ◽  
1999 ◽  
Vol 94 (1) ◽  
pp. 1-8 ◽  
Author(s):  
Laura S. Haneline ◽  
Troy A. Gobbett ◽  
Rema Ramani ◽  
Madeleine Carreau ◽  
Manuel Buchwald ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell ◽  
Cell Function ◽  
Genetic Disorder ◽  
Test Cell ◽  
Hematopoietic Stem ◽  
Murine Homologue ◽  
Complex Genetic Disorder

Fanconi anemia (FA) is a complex genetic disorder characterized by progressive bone marrow (BM) aplasia, chromosomal instability, and acquisition of malignancies, particularly myeloid leukemia. We used a murine model containing a disruption of the murine homologue ofFANCC (FancC) to evaluate short- and long-term multilineage repopulating ability of FancC −/− cells in vivo. Competitive repopulation assays were conducted where “test”FancC −/− or FancC +/+ BM cells (expressing CD45.2) were cotransplanted with congenic competitor cells (expressing CD45.1) into irradiated mice. In two independent experiments, we determined that FancC −/− BM cells have a profound decrease in short-term, as well as long-term, multilineage repopulating ability. To determine quantitatively the relative production of progeny cells by each test cell population, we calculated test cell contribution to chimerism as compared with 1 × 105 competitor cells. We determined that FancC −/− cells have a 7-fold to 12-fold decrease in repopulating ability compared with FancC +/+cells. These data indicate that loss of FancC function results in reduced in vivo repopulating ability of pluripotential hematopoietic stem cells, which may play a role in the development of the BM failure in FA patients. This model system provides a powerful tool for evaluation of experimental therapeutics on hematopoietic stem cell function.

scholarly journals New genetic tools for the in vivo study of hematopoietic stem cell function

2018 ◽  
Vol 61 ◽  
pp. 26-35 ◽  
Author(s):  
Samik Upadhaya ◽  
Boris Reizis ◽  
Catherine M. Sawai
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell ◽  
Cell Function ◽  
In Vivo Study ◽  
Hematopoietic Stem ◽  
Genetic Tools

Regulation of murine hematopoietic stem cell proliferation in vivo

2000 ◽  
Vol 28 (7) ◽  
pp. 118
Author(s):  
Y. Zhao ◽  
Y. Zhan ◽  
Y. Lin ◽  
J. Yang ◽  
D.E. Harrison ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Stem Cell ◽  
Hematopoietic Stem Cell ◽  
Hematopoietic Stem ◽  
Stem Cell Proliferation ◽  
Murine Hematopoietic Stem Cell

scholarly journals ZFP521 regulates murine hematopoietic stem cell function and facilitates MLL-AF9 leukemogenesis in mouse and human cells

Blood ◽  
2017 ◽  
Vol 130 (5) ◽  
pp. 619-624 ◽  
Author(s):  
Brian S. Garrison ◽  
Adrian P. Rybak ◽  
Isabel Beerman ◽  
Balthasar Heesters ◽  
Francois E. Mercier ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell ◽  
Cell Function ◽  
Human Cells ◽  
Self Renewal ◽  
Hematopoietic Stem ◽  
Key Points ◽  
Murine Hematopoietic Stem Cell

Key Points ZFP521 regulates HSC self-renewal and differentiation. ZFP521 facilitates leukemogenesis in an MLL-AF9–mediated leukemia model.

scholarly journals Hedgehog Signaling Is Dispensable for Adult Murine Hematopoietic Stem Cell Function and Hematopoiesis

2009 ◽  
Vol 4 (6) ◽  
pp. 559-567 ◽  
Author(s):  
Inga Hofmann ◽  
Elizabeth H. Stover ◽  
Dana E. Cullen ◽  
Junhao Mao ◽  
Kelly J. Morgan ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell ◽  
Hedgehog Signaling ◽  
Cell Function ◽  
Hematopoietic Stem ◽  
Murine Hematopoietic Stem Cell

Characterization of Hematopoietic Stem Cell Function and Sensitivity in the Homologous Recombination Deficient Exonuclease1mut Mouse Model

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 1293-1293
Author(s):  
Amar Desai ◽  
Yulan Qing ◽  
Stanton L. Gerson
Keyword(s):  
Dna Repair ◽  
Stem Cell ◽  
Homologous Recombination ◽  
Hematopoietic Stem Cell ◽  
Cell Function ◽  
Conflicts Of Interest ◽  
Strand Break ◽  
Hematopoietic Stem ◽  
Quiescent Hscs

Abstract Abstract 1293 Hematopoietic stem cell (HSC) maintenance is essential for sustained longevity and tissue function. The HSC population has lifelong self-renewing capabilities and gives rise to subsets of multipotent progenitor cells, and in turn a progeny of terminally differentiated mature cells consisting of all subtypes of the myeloid and lymphoid lineages. Long term reconstituting HSCs are necessary to replace these differentiated cells after losses caused by normal degradation or damage accumulation, with failure to replenish these stores being linked to a variety of human pathogeneses as well as aging phenotypes. HSC populations require functional DNA repair pathways in order to maintain their reconstitution capabilities but little is known about the pathways involved or the mechanism of regulation. While the majority of HSCs are quiescent at steady state, endogenous or exogenous stress can force these cells into proliferation, and previous evidence has suggested that the HSC reliance on DNA repair changes with this mobilization. Quiescent HSCs are believed to depend on non-homologous end joining (NHEJ) for repair but prior literature has shown that once forced into cycle, the DNA repair dependency shifts and is shared between homologous recombination (HR) and NHEJ. We use Exo1 deficiency as a model for homologous recombination loss in mice and demonstrate in vivo that HR is dispensable in quiescent HSCs. This is in contrast to loss of the complementary double strand break repair pathway NHEJ which has been shown to result in severe defects in HSC function. However when we force mobilize HSCs into cycle in vivo using the anti metabolite 5-fluorouracil we are able to demonstrate that the HR defects become detrimental to the animal as shown by increased cellular IR sensitivity and subsequent animal death. Additionally we use competitive repopulation studies to show that indeed the Exo1mut HSC population is more radiation sensitive after forced mobilization. This work begins to elucidate the consequences of the loss of homologous recombination in hematopoietic stem cells as well as the interplay between cell cycle status and DNA repair dependency. Disclosures: No relevant conflicts of interest to declare.

Regulation of murine hematopoietic stem cell proliferation in vivo

2000 ◽  
Vol 28 (7) ◽  
pp. 122
Author(s):  
Y. Zhao ◽  
Y. Zhan ◽  
Y. Lin ◽  
J. Yang ◽  
D.E. Harrison ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Stem Cell ◽  
Hematopoietic Stem Cell ◽  
Hematopoietic Stem ◽  
Stem Cell Proliferation ◽  
Murine Hematopoietic Stem Cell

scholarly journals Osteomacs interact with megakaryocytes and osteoblasts to regulate murine hematopoietic stem cell function

2017 ◽  
Vol 1 (26) ◽  
pp. 2520-2528 ◽  
Author(s):  
Safa F. Mohamad ◽  
Linlin Xu ◽  
Joydeep Ghosh ◽  
Paul J. Childress ◽  
Irushi Abeysekera ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell ◽  
Cell Function ◽  
Hematopoietic Stem ◽  
Key Points ◽  
Murine Hematopoietic Stem Cell

Key Points OM, osteoblast, and megakaryocyte interactions regulate HSC function in the niche. OMs differ functionally and phenotypically from BM-derived macrophages.

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