scholarly journals Assessing Cell Cycle Progression of Neural Stem and Progenitor Cells in the Mouse Developing Brain after Genotoxic Stress

10.3791/51209 ◽  
2014 ◽  
Author(s):  
Olivier Etienne ◽  
Amandine Bery ◽  
Telma Roque ◽  
Chantal Desmaze ◽  
François D. Boussin
Keyword(s):  
Cell Cycle ◽  
Progenitor Cells ◽  
Cell Cycle Progression ◽  
Genotoxic Stress ◽  
Developing Brain ◽  
Cycle Progression ◽  
Stem And Progenitor Cells

scholarly journals Developmental HCN channelopathy results in decreased neural progenitor proliferation and microcephaly in mice

2021 ◽  
Author(s):  
Anna Katharina Schlusche ◽  
Sabine Ulrike Vay ◽  
Niklas Kleinenkuhnen ◽  
Steffi Sandke ◽  
Rafael Campos-Martin ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Division ◽  
Membrane Potential ◽  
Cell Cycle Progression ◽  
Cortical Development ◽  
General Mechanism ◽  
Hcn Channel ◽  
Cycle Progression ◽  
Channel Function ◽  
Stem And Progenitor Cells

ABSTRACTThe development of the cerebral cortex relies on the controlled division of neural stem and progenitor cells. The requirement for precise spatiotemporal control of proliferation and cell fate places a high demand on the cell division machinery, and defective cell division can cause microcephaly and other brain malformations. Cell-extrinsic and intrinsic factors govern the capacity of cortical progenitors to produce large numbers of neurons and glia within a short developmental time window. In particular, ion channels shape the intrinsic biophysical properties of precursor cells and neurons and control their membrane potential throughout the cell cycle. We found that hyperpolarization-activated cyclic nucleotide-gated cation (HCN)-channel subunits are expressed in mouse, rat, and human neural progenitors. Loss of HCN-channel function in rat neural stem cells impaired their proliferation by affecting the cell-cycle progression, causing G1 accumulation and dysregulation of genes associated with human microcephaly. Transgene-mediated, dominant-negative loss of HCN-channel function in the embryonic mouse telencephalon resulted in pronounced microcephaly. Together, our findings suggest a novel role for HCN-channel subunits as a part of a general mechanism influencing cortical development in mammals.Significance StatementImpaired cell cycle regulation of neural stem and progenitor cells can affect cortical development and cause microcephaly. During cell cycle progression, the cellular membrane potential changes through the activity of ion channels and tends to be more depolarized in proliferating cells. HCN channels, which mediate a depolarizing current in neurons and cardiac cells, are linked to neurodevelopmental diseases, also contribute to the control of cell-cycle progression and proliferation of neuronal precursor cells. In this study, HCN-channel deficiency during embryonic and fetal brain development resulted in marked microcephaly of mice designed to be deficient in HCN-channel function in dorsal forebrain progenitors. The findings suggest that HCN-channel subunits are part of a general mechanism influencing cortical development in mammals.

scholarly journals Activation of Evi1 inhibits cell cycle progression and differentiation of hematopoietic progenitor cells

Leukemia ◽  
2012 ◽  
Vol 27 (5) ◽  
pp. 1127-1138 ◽  
Author(s):  
O S Kustikova ◽  
A Schwarzer ◽  
M Stahlhut ◽  
M H Brugman ◽  
T Neumann ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Progenitor Cells ◽  
Cell Cycle Progression ◽  
Hematopoietic Progenitor Cells ◽  
Hematopoietic Progenitor ◽  
Cycle Progression

Cell cycle progression is required for nuclear migration of neural progenitor cells

2006 ◽  
Vol 1088 (1) ◽  
pp. 57-67 ◽  
Author(s):  
Masaki Ueno ◽  
Kei-ichi Katayama ◽  
Hirofumi Yamauchi ◽  
Hiroyuki Nakayama ◽  
Kunio Doi
Keyword(s):  
Cell Cycle ◽  
Progenitor Cells ◽  
Cell Cycle Progression ◽  
Neural Progenitor Cells ◽  
Nuclear Migration ◽  
Neural Progenitor ◽  
Cycle Progression

scholarly journals Nucleophosmin Regulates Cell Cycle Progression and Stress Response in Hematopoietic Stem/Progenitor Cells

2006 ◽  
Vol 281 (24) ◽  
pp. 16536-16545 ◽  
Author(s):  
June Li ◽  
Daniel P. Sejas ◽  
Reena Rani ◽  
Tara Koretsky ◽  
Grover C. Bagby ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Stress Response ◽  
Progenitor Cells ◽  
Cell Cycle Progression ◽  
Cycle Progression ◽  
Hematopoietic Stem

scholarly journals The CWI Pathway: A Versatile Toolbox to Arrest Cell-Cycle Progression

2021 ◽  
Vol 7 (12) ◽  
pp. 1041
Author(s):  
Inma Quilis ◽  
Mercè Gomar-Alba ◽  
Juan Carlos Igual
Keyword(s):  
Cell Cycle ◽  
Cell Wall ◽  
Cellular Response ◽  
Cell Cycle Progression ◽  
Genetic Material ◽  
Regulatory System ◽  
Genotoxic Stress ◽  
Dna Integrity ◽  
Cycle Progression ◽  
Reciprocal Regulation

Cell-signaling pathways are essential for cells to respond and adapt to changes in their environmental conditions. The cell-wall integrity (CWI) pathway of Saccharomyces cerevisiae is activated by environmental stresses, compounds, and morphogenetic processes that compromise the cell wall, orchestrating the appropriate cellular response to cope with these adverse conditions. During cell-cycle progression, the CWI pathway is activated in periods of polarized growth, such as budding or cytokinesis, regulating cell-wall biosynthesis and the actin cytoskeleton. Importantly, accumulated evidence has indicated a reciprocal regulation of the cell-cycle regulatory system by the CWI pathway. In this paper, we describe how the CWI pathway regulates the main cell-cycle transitions in response to cell-surface perturbance to delay cell-cycle progression. In particular, it affects the Start transcriptional program and the initiation of DNA replication at the G1/S transition, and entry and progression through mitosis. We also describe the involvement of the CWI pathway in the response to genotoxic stress and its connection with the DNA integrity checkpoint, the mechanism that ensures the correct transmission of genetic material and cell survival. Thus, the CWI pathway emerges as a master brake that stops cell-cycle progression when cells are coping with distinct unfavorable conditions.

Nucleophosmin Regulates Differentiation, Cell Cycle Progression, and Stress Response in Hematopoietic Progenitor Cells.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 312-312
Author(s):  
June Li ◽  
Daniel P. Sejas ◽  
Qishen Pang
Keyword(s):  
Cell Cycle ◽  
Bone Marrow ◽  
Stress Response ◽  
Progenitor Cells ◽  
Cell Cycle Progression ◽  
Proliferative Potential ◽  
Hematopoietic Progenitors ◽  
Cycle Progression ◽  
Hematopoietic Stem ◽  
Empty Vector

Abstract Nucleophosmin (NPM) is a multifunctional protein frequently overexpressed in actively proliferating cells including tumor and hematopoietic stem cells. Strong evidence indicates that NPM is involved in hematopoiesis and leukemic development. Here we report that NPM enhances the proliferative potential of hematopoietic stem/progenitor cells and increases cell survival upon stress challenge. Specifically, lin-Sca1+c-kit+ bone marrow cells transduced with retroviral vector expressing NPM exhibited higher proliferative rates in both short-term liquid culture and clonogenic progenitor cell assays, compared to the cells transduced with empty vector. Interestingly, NPM overexpression appears to inhibit differentiation of myeloid progenitors. Hematopoietic stem/progenitor cells infected with the NPM retrovirus expressed significantly lower levels of mature cell markers Gr-1 and Mac-1 compared to empty vector transduced cells, and majority of the NPM-overexpressing cells remained Sca1+C-Kit+ during the 5-day culture. Bone marrow transplantation experiments demonstrated that NPM overexpression increases long-term multi-lineage repopulating capacity of hematopoietic progenitors. We have not observed any evidence of proliferative disorders or leukemia in recipients transplanted with NPM-expressing progenitors thus far (4 months posttransplantation). Through cell-cycle profile analysis and single-cell division experiments, we showed that NPM overexpression induces rapid entry of hematopoietic progenitors into the cell cycle, probably via promoting G0/G1 to S transition. Furthermore, immunocytochemical and Western-blot analyses demonstrated that NPM-transduced cells expressed higher level of cyclin A compared to vector-transduced cells. Finally, overexpression of NPM significantly increased the survival of hematopoietic progenitors exposed to mitomycin C or hydrogen peroxide, suggesting that NPM can protect cells from DNA damage and oxidative stress. Together, these results indicate that NPM plays an important role in hematopoiesis via mechanisms involving modulation of progenitor differentiation, cell cycle progression, and stress response.

Induction of CABLES1 by the TKI Inhibits the Cell Cycle Progression and Induces Apoptosis In CML Cell.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 1199-1199
Author(s):  
Tomonari Takemura ◽  
Satoki Nakamura ◽  
Yasuyuki Nagata ◽  
Daisuke Yokota ◽  
Isao Hirano ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Bone Marrow ◽  
Cell Proliferation ◽  
Progenitor Cells ◽  
Cell Lines ◽  
Cell Cycle Progression ◽  
Kinase Inhibitors ◽  
Cycle Progression ◽  
Abl Kinase ◽  
Abl Kinase Inhibitors

Abstract Abstract 1199 [Background and Aims] CABLES1 (cyclin-dependent kinase (CDK)-5 and ABL enzyme 1) is a regulator of cell proliferation, apoptosis, and cell cycle, and it has been reported to be lost in a variety cancers. It has been also reported that knockout of the Cable1 gene has minimal to no effect on hematopoietic stem cells. However, we found that the expression of Cables1 gene and CABLES1 protein was suppressed in CML cells, and its function is little known in CML. In this study, we have investigated the function of CABLES1 in CML cell proliferation. [Methods] The cells used in this study were human CML cell lines, K562, Meg01 and SHG3 cells. Primary CML cells (ALDHhi cells) were obtained from the bone marrow of CML (CP) patients (n=12). Human normal ALDHhi cells were isolated from bone marrow of healthy volunteers after obtaining informed consents. For analysis of Cables1 mRNA expression, quantitative RT-PCR was performed in all cell lines treated with Abl kinase inhibitors (STI571, AMN107, and BMS354825). For cell survival analysis and the levels of p53 and some CDKIs in CML cells, MTT assays, western blot and cell cycle analysis were performed in all cell lines transfected with Cables1 shRNA or cDNA. For colony analysis, the colonies of CFU-GEMM, CFU-GM, and BFU-E were counted in CML stem/progenitor cells transfected with Cables1 cDNA or shiRNA, or treated with Abl kinase inhibitors. [Results] In CML cell lines, the expressions of Cables1 mRNA and CABLES1 protein were significantly increased by treatment with Abl kinase inhibitors or transfection with Bcr-Abl shRNA. In CML cells transfected with the Cables1 cDNA, it is shown that CML cell proliferation was inhibited, and the phosphorylation levels of p53, and the expression of BAX and p21 protein were markedly increased compared to the untransfected cells. In addition, the overexpression of CABLES1 induced G1 cell cycle arrest and reduced the DiOC6 fluorescence, indicating breakdown of the mitochondrial membrane potential in CML cells. On the other hand, the changes of p73 and p27 protein expression were not detected. Moreover, in CML cells transfected with Cables1 shRNA, the inhibition of CML cell proliferation by the Abl kinase inhibitors were weakened. In CML stem/progenitor cells (ALDHhi cells) obtained from patients with CML, the expression of Cables1 mRNA was suppressed, and the transfection with Bcr-Abl shRNA or treatment with Abl kinase inhibitors increased the expression of Cables1 mRNA and CABLES1 protein, and decreased the counts of CFU-GEMM, CFU-GM and BFU-E. [Conclusion] Our results demonstrated that the Bcr-Abl suppressed the expression of CABLES1, and the depletion of CABLES1 promotes cell cycle progression and p53-dependent apoptosis. Moreover, the induction of CABLES1 expression has the potentiality to eradicate CML stem/progenitor cells. Disclosures: No relevant conflicts of interest to declare.

Sign in / Sign up

Export Citation Format

Share Document