scholarly journals Gene expression fluctuations in murine hematopoietic stem cells with cell cycle progression

2007 ◽  
Vol 214 (3) ◽  
pp. 786-795 ◽  
Author(s):  
Gerri J. Dooner ◽  
Gerald A. Colvin ◽  
Mark S. Dooner ◽  
Kevin W. Johnson ◽  
Peter J. Quesenberry
Keyword(s):  
Gene Expression ◽  
Cell Cycle ◽  
Stem Cells ◽  
Hematopoietic Stem Cells ◽  
Cell Cycle Progression ◽  
Cycle Progression ◽  
Hematopoietic Stem

scholarly journals Expression of Cell Cycle–Related Genes With Cytokine-Induced Cell Cycle Progression of Primitive Hematopoietic Stem Cells

2010 ◽  
Vol 19 (4) ◽  
pp. 453-460 ◽  
Author(s):  
Peter J. Quesenberry ◽  
Gerri J. Dooner ◽  
Michael Del Tatto ◽  
Gerald A. Colvin ◽  
Kevin Johnson ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Stem Cells ◽  
Hematopoietic Stem Cells ◽  
Cell Cycle Progression ◽  
Cycle Progression ◽  
Hematopoietic Stem

CCND1–CDK4–mediated cell cycle progression provides a competitive advantage for human hematopoietic stem cells in vivo

2015 ◽  
Vol 210 (2) ◽  
pp. 2102OIA144
Author(s):  
Nicole Mende ◽  
Erika E Kuchen ◽  
Mathias Lesche ◽  
Tatyana Grinenko ◽  
Konstantinos D Kokkaliaris ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Stem Cells ◽  
Hematopoietic Stem Cells ◽  
Competitive Advantage ◽  
Cell Cycle Progression ◽  
Cycle Progression ◽  
Hematopoietic Stem

scholarly journals Stroma-Derived Connective Tissue Growth Factor Maintains Cell Cycle Progression and Repopulation Activity of Hematopoietic Stem Cells In Vitro

2015 ◽  
Vol 5 (5) ◽  
pp. 702-715 ◽  
Author(s):  
Rouzanna Istvánffy ◽  
Baiba Vilne ◽  
Christina Schreck ◽  
Franziska Ruf ◽  
Charlotta Pagel ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Stem Cells ◽  
Growth Factor ◽  
Connective Tissue ◽  
Hematopoietic Stem Cells ◽  
Cell Cycle Progression ◽  
Tissue Growth ◽  
Cycle Progression ◽  
Hematopoietic Stem

Prolonged Expression of c-fos Suppresses Cell Cycle Entry of Dormant Hematopoietic Stem Cells

Blood ◽  
1999 ◽  
Vol 93 (3) ◽  
pp. 816-825 ◽  
Author(s):  
Seiji Okada ◽  
Tetsuya Fukuda ◽  
Kunimasa Inada ◽  
Takeshi Tokuhisa
Keyword(s):  
Cell Cycle ◽  
Stem Cells ◽  
Hematopoietic Stem Cells ◽  
Colony Formation ◽  
Cell Cycle Progression ◽  
Fetal Liver ◽  
Cycle Progression ◽  
Hematopoietic Stem ◽  
Fetal Liver Cells ◽  
Deficient Mice

The proto-oncogene c-fos was transiently upregulated in primitive hematopoietic stem (Lin−Sca-1+) cells stimulated with stem cell factor, interleukin-3 (IL-3), and IL-6. To investigate a role of the c-fos in hematopoietic stem cells, we used bone marrow (BM) cells from transgenic mice carrying the c-fos gene under the control of the interferon-/β–inducible Mx-promoter (Mx–c-fos), and fetal liver cells from c-fos–deficient mice. Prolonged expression of the c-fos in Lin−Sca-1+ BM cells inhibited factor-dependent colony formation and hematopoiesis on a stromal cell layer by keeping them at G0/G1 phase of the cell cycle. These Lin−Sca-1+ BM cells on a stromal layer entered into the cell cycle whenever exogenous c-fos was downregulated. However, ectopic c-fos did not perturb colony formation by Lin−Sca-1+ BM cells after they entered the cell cycle. Furthermore, endogenous c-fos is not essential to cell cycle progression of hematopoietic stem cells because the factor-dependent and the stroma-dependent hematopoiesis by Lin−Sca-1+ fetal liver cells from c-fos–deficient mice was not impaired. These results suggest that the c-fos induced in primitive hematopoietic stem cells negatively controls cell cycle progression and maintains them in a dormant state.

Cell cycle progression and fate decisions in hematopoietic stem cells

2017 ◽  
Vol 53 ◽  
pp. S102
Author(s):  
Tatyana Grinenko ◽  
Anne Eugster ◽  
Lars Thielecke ◽  
Ingmar Glauche ◽  
Onur Basak ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Stem Cells ◽  
Hematopoietic Stem Cells ◽  
Cell Cycle Progression ◽  
Cycle Progression ◽  
Hematopoietic Stem

Prolonged Expression of c-fos Suppresses Cell Cycle Entry of Dormant Hematopoietic Stem Cells

Blood ◽  
1999 ◽  
Vol 93 (3) ◽  
pp. 816-825 ◽  
Author(s):  
Seiji Okada ◽  
Tetsuya Fukuda ◽  
Kunimasa Inada ◽  
Takeshi Tokuhisa
Keyword(s):  
Cell Cycle ◽  
Stem Cells ◽  
Hematopoietic Stem Cells ◽  
Colony Formation ◽  
Cell Cycle Progression ◽  
Fetal Liver ◽  
Cycle Progression ◽  
Hematopoietic Stem ◽  
Fetal Liver Cells ◽  
Deficient Mice

Abstract The proto-oncogene c-fos was transiently upregulated in primitive hematopoietic stem (Lin−Sca-1+) cells stimulated with stem cell factor, interleukin-3 (IL-3), and IL-6. To investigate a role of the c-fos in hematopoietic stem cells, we used bone marrow (BM) cells from transgenic mice carrying the c-fos gene under the control of the interferon-/β–inducible Mx-promoter (Mx–c-fos), and fetal liver cells from c-fos–deficient mice. Prolonged expression of the c-fos in Lin−Sca-1+ BM cells inhibited factor-dependent colony formation and hematopoiesis on a stromal cell layer by keeping them at G0/G1 phase of the cell cycle. These Lin−Sca-1+ BM cells on a stromal layer entered into the cell cycle whenever exogenous c-fos was downregulated. However, ectopic c-fos did not perturb colony formation by Lin−Sca-1+ BM cells after they entered the cell cycle. Furthermore, endogenous c-fos is not essential to cell cycle progression of hematopoietic stem cells because the factor-dependent and the stroma-dependent hematopoiesis by Lin−Sca-1+ fetal liver cells from c-fos–deficient mice was not impaired. These results suggest that the c-fos induced in primitive hematopoietic stem cells negatively controls cell cycle progression and maintains them in a dormant state.

scholarly journals CCND1–CDK4–mediated cell cycle progression provides a competitive advantage for human hematopoietic stem cells in vivo

2015 ◽  
Vol 212 (8) ◽  
pp. 1171-1183 ◽  
Author(s):  
Nicole Mende ◽  
Erika E. Kuchen ◽  
Mathias Lesche ◽  
Tatyana Grinenko ◽  
Konstantinos D. Kokkaliaris ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Stem Cells ◽  
Hematopoietic Stem Cells ◽  
Competitive Advantage ◽  
Cell Cycle Progression ◽  
Cycle Phase ◽  
Cycle Progression ◽  
Hematopoietic Stem ◽  
Human Hscs

Maintenance of stem cell properties is associated with reduced proliferation. However, in mouse hematopoietic stem cells (HSCs), loss of quiescence results in a wide range of phenotypes, ranging from functional failure to extensive self-renewal. It remains unknown whether the function of human HSCs is controlled by the kinetics of cell cycle progression. Using human HSCs and human progenitor cells (HSPCs), we report here that elevated levels of CCND1–CDK4 complexes promoted the transit from G0 to G1 and shortened the G1 cell cycle phase, resulting in protection from differentiation-inducing signals in vitro and increasing human leukocyte engraftment in vivo. Further, CCND1–CDK4 overexpression conferred a competitive advantage without impacting HSPC numbers. In contrast, accelerated cell cycle progression mediated by elevated levels of CCNE1–CDK2 led to the loss of functional HSPCs in vivo. Collectively, these data suggest that the transition kinetics through the early cell cycle phases are key regulators of human HSPC function and important for lifelong hematopoiesis.

Valproic Acid Accelerates Cell Cycle Progression of Hematopoietic Stem Cells Via the Activation of GSK3beta-Dependent Signaling Pathways.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 1708-1708
Author(s):  
Gesine Bug ◽  
Hilal Gul ◽  
Kerstin Schwarz ◽  
Manuela Kampfmann ◽  
Xiaomin Zheng ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Stem Cells ◽  
Valproic Acid ◽  
Wnt Signaling ◽  
Cell Cycle Progression ◽  
Beta Catenin ◽  
Cycle Progression ◽  
Hematopoietic Stem ◽  
Cd34 Cells ◽  
Colony Assays

Abstract Histone deacetylase inhibitors (HDI) have attracted considerable attention because of their ability to overcome the differentiation block in leukemic blasts either alone, or in combination with differentiating agents such as all-trans retinoic acid (ATRA). We have previously reported favorable effects of the potent HDI valproic acid (VPA) in combination with ATRA in a small subset of patients with advanced acute myeloid leukemia (AML) leading to blast cell reduction and improvement of hemoglobin. This effect was accompanied by hypergranulocytosis most likely due to an enhancement of non-leukemic myelopoiesis and suppression of malignant hematopoiesis rather than enforced differentiation of leukemic cells. These data prompted us to investigate the impact of VPA on normal hematopoietic stem cells (HSC). Differentiation of cord blood-derived, purified CD34+ cells was assessed by FACS analysis after a 7-days suspension culture in presence of early acting cytokines and 30–150μg/mL VPA. VPA prevented differentation of CD34+ cells in a dose-dependent manner: concomitant with an increase of CD34+ cells from 17 to 47%, the proportion of monocytic CD14+ cells decreased from 27 to 3% (n=3). In addition, VPA induced a 30-fold amplification of CD34+ bone marrow (BM) cells within 10 days as determined by colony assays (n=3). To evaluate the functional capacity of VPA-treated HSC, murine Sca1+/lin−s cells were harvested from colony assays and replated. VPA treatment allowed up to four cycles of replating in contrast to VPA-naïve control cells. Further analysis demonstrated that the stimulatory effect of VPA on the in vitro growth and colony formation capacity of HSC was mainly due to accelerated cell cycle progression. VPA strongly increased the proportion of cells in S phase compared to untreated controls (38 vs. 17%, resp.), as detected by propidium iodid staining and BRDU incorporation as well as reduced expression of the CDK-inhibitor p21cip-1/waf using murine HSC after 7 days of culture. Downregulation of p21cip-1/waf was confirmed in CD34+ BM cells showing maximum inhibition after 48 hours of VPA treatment and no recovery thereafter. Recent results indicate that VPA exerts inhibitory activity on GSK3beta by phosphorylation on Ser-9 and stimulates Akt in human neuroblastoma cells. GSK3beta is an effector of the Wnt-signaling pathway located upstream of beta-catenin. Wnt-signaling can directly stimulate the proliferation of HSC, expand the HSC pool and lead to upregulation of HoxB4. Here we show that VPA increased the inhibition-associated phosphorylation of GSK3beta on Ser-9 in human CD34+ BM cells after 48 hours as well as in murine Sca1+/lin− cells after 7 days. Exposure to VPA enhanced beta-catenin and Akt activity not only in CD34+ HSC but also in KG-1 and TF-1 cells with maximum activation after 48 hours of VPA stimulation. Moreover, VPA lead to an 8-fold increase of the HoxB4 level in CD34+ BM cells as determined by real time PCR at 48 hours. In conclusion, we show that VPA i.) expands HSC as assesed by phenotype and function; ii.) accelerates cell cycle progression of HSC accompanied by the down-regulation of p21cip-1waf; iii.) activates the GSK3beta depending beta-catenin pathway and Akt and iv.) up-regulates HoxB4. Our data strongly suggest that VPA is able to influence some of the signaling pathway considered relevant for proliferation and self-renewal which might request reconsideration of their employment for the treatment of AML.

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