scholarly journals The Cyclin-Dependent Kinase Inhibitor p27kip1Regulates Radial Stem Cell Quiescence and Neurogenesis in the Adult Hippocampus

Stem Cells ◽  
2014 ◽  
Vol 33 (1) ◽  
pp. 219-229 ◽  
Author(s):  
Zoraida Andreu ◽  
Muhammad Amir Khan ◽  
Pilar González-Gómez ◽  
Santiago Negueruela ◽  
Rafael Hortigüela ◽  
...  
Keyword(s):  
Stem Cell ◽  
Kinase Inhibitor ◽  
Cyclin Dependent Kinase ◽  
Cyclin Dependent Kinase Inhibitor ◽  
Stem Cell Quiescence ◽  
Cell Quiescence ◽  
Adult Hippocampus

scholarly journals Identification of novel regulators of hematopoietic stem cell development through refinement of stem cell localization and expression profiling

Blood ◽  
2009 ◽  
Vol 114 (21) ◽  
pp. 4645-4653 ◽  
Author(s):  
Maria I. Mascarenhas ◽  
Aimée Parker ◽  
Elaine Dzierzak ◽  
Katrin Ottersbach
Keyword(s):  
Gene Expression ◽  
Stem Cell ◽  
Expression Profiling ◽  
Gene Expression Analysis ◽  
Kinase Inhibitor ◽  
Cyclin Dependent Kinase ◽  
Hematopoietic Stem ◽  
Cyclin Dependent Kinase Inhibitor ◽  
Cell Localization ◽  
Before And After

Abstract The first adult-repopulating hematopoietic stem cells (HSCs) are detected starting at day 10.5 of gestation in the aorta-gonads-mesonephros (AGM) region of the mouse embryo. Despite the importance of the AGM in initiating HSC production, very little is currently known about the regulators that control HSC emergence in this region. We have therefore further defined the location of HSCs in the AGM and incorporated this information into a spatial and temporal comparative gene expression analysis of the AGM. The comparisons included gene expression profiling (1) in the newly identified HSC-containing region compared with the region devoid of HSCs, (2) before and after HSC emergence in the AGM microenvironment, and (3) on populations enriched for HSCs and their putative precursors. Two genes found to be up-regulated at the time and place where HSCs are first detected, the cyclin-dependent kinase inhibitor p57Kip2/Cdkn1c and the insulin-like growth factor 2, were chosen for further analysis. We demonstrate here that they play a novel role in AGM hematopoiesis. Interestingly, many genes involved in the development of the tissues surrounding the dorsal aorta are also up-regulated during HSC emergence, suggesting that the regulation of HSC generation occurs in coordination with the development of other organs.

scholarly journals Cyclin-Dependent Kinase Inhibitor p21 Controls Adult Neural Stem Cell Expansion by Regulating Sox2 Gene Expression

2013 ◽  
Vol 12 (1) ◽  
pp. 88-100 ◽  
Author(s):  
M. Ángeles Marqués-Torrejón ◽  
Eva Porlan ◽  
Ana Banito ◽  
Esther Gómez-Ibarlucea ◽  
Andrés J. Lopez-Contreras ◽  
...  
Keyword(s):  
Gene Expression ◽  
Stem Cell ◽  
Neural Stem Cell ◽  
Cell Expansion ◽  
Kinase Inhibitor ◽  
Cyclin Dependent Kinase ◽  
Adult Neural Stem Cell ◽  
Stem Cell Expansion ◽  
Cyclin Dependent Kinase Inhibitor ◽  
Sox2 Gene

scholarly journals Id4 Downstream of Notch2 Maintains Neural Stem Cell Quiescence in the Adult Hippocampus

Cell Reports ◽  
2019 ◽  
Vol 28 (6) ◽  
pp. 1485-1498.e6 ◽  
Author(s):  
Runrui Zhang ◽  
Marcelo Boareto ◽  
Anna Engler ◽  
Angeliki Louvi ◽  
Claudio Giachino ◽  
...  
Keyword(s):  
Stem Cell ◽  
Neural Stem Cell ◽  
Stem Cell Quiescence ◽  
Cell Quiescence ◽  
Adult Hippocampus

scholarly journals Hepatic leukemia factor is a novel leukemic stem cell regulator in DNMT3A, NPM1, and FLT3-ITD triple-mutated AML

Blood ◽  
2019 ◽  
Vol 134 (3) ◽  
pp. 263-276 ◽  
Author(s):  
Swati Garg ◽  
Armando Reyes-Palomares ◽  
Lixiazi He ◽  
Anne Bergeron ◽  
Vincent-Philippe Lavallée ◽  
...  
Keyword(s):  
Stem Cell ◽  
Cell Sorting ◽  
Myeloid Leukemia ◽  
Kinase Inhibitor ◽  
Cyclin Dependent Kinase ◽  
Poor Survival ◽  
Transcription Start ◽  
Leukemia Stem Cell ◽  
Cyclin Dependent Kinase Inhibitor ◽  
Enhancer Of Split

Abstract FLT3, DNMT3A, and NPM1 are the most frequently mutated genes in cytogenetically normal acute myeloid leukemia (AML), but little is known about how these mutations synergize upon cooccurrence. Here we show that triple-mutated AML is characterized by high leukemia stem cell (LSC) frequency, an aberrant leukemia-specific GPR56highCD34low immunophenotype, and synergistic upregulation of Hepatic Leukemia Factor (HLF). Cell sorting based on the LSC marker GPR56 allowed isolation of triple-mutated from DNMT3A/NPM1 double-mutated subclones. Moreover, in DNMT3A R882-mutated patients, CpG hypomethylation at the HLF transcription start site correlated with high HLF mRNA expression, which was itself associated with poor survival. Loss of HLF via CRISPR/Cas9 significantly reduced the CD34+GPR56+ LSC compartment of primary human triple-mutated AML cells in serial xenotransplantation assays. HLF knockout cells were more actively cycling when freshly harvested from mice, but rapidly exhausted when reintroduced in culture. RNA sequencing of primary human triple-mutated AML cells after shRNA-mediated HLF knockdown revealed the NOTCH target Hairy and Enhancer of Split 1 (HES1) and the cyclin-dependent kinase inhibitor CDKN1C/p57 as novel targets of HLF, potentially mediating these effects. Overall, our data establish HLF as a novel LSC regulator in this genetically defined high-risk AML subgroup.

scholarly journals CHD7 Maintains Neural Stem Cell Quiescence and Prevents Premature Stem Cell Depletion in the Adult Hippocampus

Stem Cells ◽  
2014 ◽  
Vol 33 (1) ◽  
pp. 196-210 ◽  
Author(s):  
Kieran M. Jones ◽  
Nemanja Sarić ◽  
John P. Russell ◽  
Cynthia L. Andoniadou ◽  
Peter J. Scambler ◽  
...  
Keyword(s):  
Stem Cell ◽  
Neural Stem Cell ◽  
Cell Depletion ◽  
Stem Cell Quiescence ◽  
Cell Quiescence ◽  
Adult Hippocampus

Stem-cell ageing modified by the cyclin-dependent kinase inhibitor p16INK4a

Nature ◽  
2006 ◽  
Vol 443 (7110) ◽  
pp. 421-426 ◽  
Author(s):  
Viktor Janzen ◽  
Randolf Forkert ◽  
Heather E. Fleming ◽  
Yoriko Saito ◽  
Michael T. Waring ◽  
...  
Keyword(s):  
Stem Cell ◽  
Kinase Inhibitor ◽  
Cyclin Dependent Kinase ◽  
Cyclin Dependent Kinase Inhibitor

scholarly journals Notch2 signaling regulates Id4 and cell cycle genes to maintain neural stem cell quiescence in the adult hippocampus

2018 ◽  
Author(s):  
Runrui Zhang ◽  
Marcelo Boareto ◽  
Anna Engler ◽  
Angeliki Louvi ◽  
Claudio Giachino ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Stem Cells ◽  
Stem Cell ◽  
Hippocampal Dentate Gyrus ◽  
Cell Cycle Genes ◽  
Stem Cell Quiescence ◽  
Activated State ◽  
Cell Quiescence ◽  
Age Dependent ◽  
Adult Hippocampus

SummaryNeural stem cells (NSCs) in the adult hippocampal dentate gyrus (DG) can be quiescent or proliferative, but how they are maintained is largely unknown. With age DG NSCs become increasingly dormant, which impinges on neuron generation. We addressed how NSC activity is controlled and found that Notch2 promotes quiescence by regulating their transition to the activated state. Notch2-ablation induces cell cycle genes and markers of active NSCs. Conversely, quiescent NSC-associated genes, including Id4, are down regulated after Notch2 deletion. We found that Notch2 binds the Id4 promoter and positively regulates transcription. Similar to Notch2, Id4 overexpression promotes DG NSC quiescence and Id4 knockdown rescues proliferation, even when Notch2 signaling is activated. We show that Notch2 regulates age-dependent DG NSC dormancy and Notch2 inhibition rejuvenates neurogenesis in the DG of aged mice. Our data indicate that a Notch2-Id4 axis promotes adult DG NSC quiescence and dormancy.

Sign in / Sign up

Export Citation Format

Share Document