Analysis of Radiation‐Induced Changes in Cell Cycle and DNA Damage of Murine Hematopoietic Stem Cells by Multi‐Color Flow Cytometry

2021 ◽  
Vol 1 (8) ◽  
Author(s):  
Debajyoti Majumdar ◽  
Eric M. Pietras ◽  
Snehalata A. Pawar
Keyword(s):  
Cell Cycle ◽  
Stem Cells ◽  
Flow Cytometry ◽  
Dna Damage ◽  
Hematopoietic Stem Cells ◽  
Color Flow ◽  
Hematopoietic Stem ◽  
Radiation Induced ◽  
Induced Changes

scholarly journals Quiescent Hematopoietic Stem Cells Accumulate DNA Damage during Aging that Is Repaired upon Entry into Cell Cycle

2014 ◽  
Vol 15 (1) ◽  
pp. 37-50 ◽  
Author(s):  
Isabel Beerman ◽  
Jun Seita ◽  
Matthew A. Inlay ◽  
Irving L. Weissman ◽  
Derrick J. Rossi
Keyword(s):  
Cell Cycle ◽  
Stem Cells ◽  
Dna Damage ◽  
Hematopoietic Stem Cells ◽  
Hematopoietic Stem

scholarly journals DNA-damage response gene GADD45A induces differentiation in hematopoietic stem cells without inhibiting cell cycle or survival

Stem Cells ◽  
2016 ◽  
Vol 34 (3) ◽  
pp. 699-710 ◽  
Author(s):  
Susanne Wingert ◽  
Frederic B. Thalheimer ◽  
Nadine Haetscher ◽  
Maike Rehage ◽  
Timm Schroeder ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Stem Cells ◽  
Dna Damage ◽  
Hematopoietic Stem Cells ◽  
Dna Damage Response ◽  
Response Gene ◽  
Hematopoietic Stem ◽  
Damage Response

Deregulated Gene Expression Pathways in Myelodysplastic Syndrome Hematopoietic Stem Cells.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 735-735 ◽  
Author(s):  
Andrea Pellagatti ◽  
Mario Cazzola ◽  
Aristoteles Giagounidis ◽  
Janet Perry ◽  
Luca Malcovati ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Cycle ◽  
Stem Cells ◽  
Dna Damage ◽  
Gene Ontology ◽  
Hematopoietic Stem Cells ◽  
Molecular Pathogenesis ◽  
Beta Catenin ◽  
Trisomy 8 ◽  
Hematopoietic Stem

Abstract Abstract 735 The myelodysplastic syndromes (MDS) are a heterogeneous group of clonal hematopoietic stem cell malignancies that are characterized by ineffective hematopoiesis resulting in peripheral cytopenias and a hypercellular bone marrow. In order to gain insight into the molecular pathogenesis of the MDS, we have determined the transcriptome of the hematopoietic stem cells (HSC) of 183 MDS patients and 17 healthy controls. The CD34+ cells obtained from MDS patients and healthy individuals were analyzed using Affymetrix U133 Plus2.0 arrays. Global pathway analysis using the Ingenuity software and the DAVID database has identified critical deregulated gene pathways and gene ontology (functional) groups perturbed in MDS HSC compared with normal HSC. The most significantly deregulated pathways in MDS include interferon signaling, thrombopoietin signaling and the Wnt pathway. Moreover, we have identified multiple pathways that are deregulated in specific MDS karyotypic groups and between early (subtype RA) and advanced MDS (subtype RAEB2). Among the most significantly deregulated gene pathways and ontology groups in early MDS are immunodeficiency, apoptosis and chemokine signaling, whereas advanced MDS is characterized by deregulation of the cell cycle, DNA damage response and checkpoint pathways. The clinical behavior of patients with del(5q), +8 or–7/del(7q) is different and we have identified distinct gene expression profiles and deregulated gene pathways for MDS defined by these major karyotypic groups. The most significantly deregulated gene pathways in del(5q) MDS include primary immunodeficiency signaling, Wnt/beta-catenin signaling, integrin signaling, cell cycle regulation and Huntington's disease signaling. Patients with the 5q- syndrome also show deregulation of the p53 pathway. Moreover, chromatin assembly and translation are among the most significant gene ontology groups in del(5q) MDS. We have found that MDS with the–7/del(7q) is characterized by deregulation of multiple pathways involved in cell survival, differentiation, apoptosis and growth, and include SAPK/JNK, NF-kB, PI3K/AKT and ceramide signaling pathways. Strikingly, all of the most significantly deregulated gene pathways in trisomy 8 MDS in our study concern or are associated with the immune response, and include B-cell receptor signaling, antigen presentation and CTLA4 signaling in Cytotoxic T lymphocytes pathways. These data are consistent with an immune system role in the pathogenesis of MDS with trisomy 8. Importantly, much of the deregulated pathway data generated in this study is in accord with the known biology of MDS. On the basis of our observations, we suggest a model for MDS in which immune deregulation and activation of apoptosis pathways in early MDS cells, consistent with clinically observed ineffective hematopoiesis, functions as a barrier to prevent leukemic transformation. Disruption of the DNA damage check points in advanced MDS results in an increase in the error rate of DNA repair with a concomitant increase in genomic instability, leading to evolution to AML. This is the first study to determine deregulated gene pathways and ontology groups in the HSC compartment of a large group of patients with MDS. The deregulated pathways identified are likely to be critical to the MDS HSC phenotype, provide important new insights into the molecular pathogenesis of this disorder, and may represent new targets for therapeutic intervention. Disclosures: No relevant conflicts of interest to declare.

scholarly journals MicroRNA 34a promotes ionizing radiation–induced DNA damage repair in murine hematopoietic stem cells

2019 ◽  
Vol 33 (7) ◽  
pp. 8138-8147 ◽  
Author(s):  
Hao Zeng ◽  
Mengjia Hu ◽  
Yukai Lu ◽  
Zihao Zhang ◽  
Yang Xu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Dna Damage ◽  
Ionizing Radiation ◽  
Hematopoietic Stem Cells ◽  
Dna Damage Repair ◽  
Hematopoietic Stem ◽  
Damage Repair ◽  
Radiation Induced

scholarly journals ¬¬Attenuated DNA Damage Responses and Increased Apoptosis Characterize Human Hematopoietic Stem Cells Exposed to Irradiation

2018 ◽  
Vol 64 ◽  
pp. S87
Author(s):  
Michael Milyavsky ◽  
Shahar Biechonski ◽  
Leonid Olender ◽  
Adi Zipin-Roitman ◽  
Muhammad Yassin ◽  
...  
Keyword(s):  
Stem Cells ◽  
Dna Damage ◽  
Hematopoietic Stem Cells ◽  
Hematopoietic Stem ◽  
Dna Damage Responses

scholarly journals Single-cell RNA-seq reveals a concomitant delay in differentiation and cell cycle of aged hematopoietic stem cells

BMC Biology ◽  
2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Léonard Hérault ◽  
Mathilde Poplineau ◽  
Adrien Mazuel ◽  
Nadine Platet ◽  
Élisabeth Remy ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Stem Cells ◽  
Hematopoietic Stem Cells ◽  
Cell Cycle Regulators ◽  
Potential Mechanism ◽  
Rna Seq ◽  
Hematopoietic Stem ◽  
Age Related ◽  
Undifferentiated State ◽  
Reference Map

Abstract Background Hematopoietic stem cells (HSCs) are the guarantor of the proper functioning of hematopoiesis due to their incredible diversity of potential. During aging, heterogeneity of HSCs changes, contributing to the deterioration of the immune system. In this study, we revisited mouse HSC compartment and its transcriptional plasticity during aging at unicellular scale. Results Through the analysis of 15,000 young and aged transcriptomes, we identified 15 groups of HSCs revealing rare and new specific HSC abilities that change with age. The implantation of new trajectories complemented with the analysis of transcription factor activities pointed consecutive states of HSC differentiation that were delayed by aging and explained the bias in differentiation of older HSCs. Moreover, reassigning cell cycle phases for each HSC clearly highlighted an imbalance of the cell cycle regulators of very immature aged HSCs that may contribute to their accumulation in an undifferentiated state. Conclusions Our results establish a new reference map of HSC differentiation in young and aged mice and reveal a potential mechanism that delays the differentiation of aged HSCs and could promote the emergence of age-related hematologic diseases.

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
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