Molecular Signatures of Quiescent, Mobilized and Leukemia-Initiating Hematopoietic Stem Cells
Copyright policy )Molecular Signatures of Quiescent, Mobilized and Leukemia-Initiating Hematopoietic Stem Cells
Hematopoietic stem cells (HSC) are rare, multipotent cells capable of generating all specialized cells of the blood system. Appropriate regulation of HSC quiescence is thought to be crucial to maintain their lifelong function; however, the molecular pathways controlling stem cell quiescence remain poorly characterized. Likewise, the molecular events driving leukemogenesis remain elusive. In this study, we compare the gene expression profiles of steady-state bone marrow HSC to non-self-renewing multipotent progenitors; to HSC treated with mobilizing drugs that expand the HSC pool and induce egress from the marrow; and to leukemic HSC in a mouse model of chronic myelogenous leukemia. By intersecting the resulting lists of differentially regulated genes we identify a subset of molecules that are downregulated in all three circumstances, and thus may be particularly important for the maintenance and function of normal, quiescent HSC. These results identify potential key regulators of HSC and give insights into the clinically important processes of HSC mobilization for transplantation and leukemic development from cancer stem cells.
- JOSLIN DIABETES CENTER
- Harvard University United States
- University of California, San Francisco United States
- University of California San Francisco United States
- UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
Transcription, Genetic, Regenerative Medicine, Cell Transformation, Inbred C57BL, immunology, Mice, computational biology, leukocyte activation, Stem Cell Research - Nonembryonic - Human, Cardiovascular Medicine and Haematology, cell biology, bone marrow and stem cell transplantation, 2.1 Biological and endogenous factors, Chronic, Cancer, Leukemia, hematology, Reverse Transcriptase Polymerase Chain Reaction, Q, R, Nucleic Acid Hybridization, Hematology, Flow Cytometry, genetics and genomics, Blood, Cell Transformation, Neoplastic, oncology, Medicine, Stem Cell Research - Nonembryonic - Non-Human, Transcription, Research Article, 570, General Science & Technology, 1.1 Normal biological development and functioning, Science, 610, developmental biology, Rare Diseases, Genetic, stem cells, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Genetics, Animals, hematological malignancies, Transplantation, Neoplastic, Biomedical and Clinical Sciences, Animal, Inflammatory and immune system, Gene Expression Profiling, Stem Cell Research, Hematopoietic Stem Cells, hematopoiesis, Mice, Inbred C57BL, Disease Models, Animal, Gene Expression Regulation, Disease Models, BCR-ABL Positive, Generic health relevance, Myelogenous
Transcription, Genetic, Regenerative Medicine, Cell Transformation, Inbred C57BL, immunology, Mice, computational biology, leukocyte activation, Stem Cell Research - Nonembryonic - Human, Cardiovascular Medicine and Haematology, cell biology, bone marrow and stem cell transplantation, 2.1 Biological and endogenous factors, Chronic, Cancer, Leukemia, hematology, Reverse Transcriptase Polymerase Chain Reaction, Q, R, Nucleic Acid Hybridization, Hematology, Flow Cytometry, genetics and genomics, Blood, Cell Transformation, Neoplastic, oncology, Medicine, Stem Cell Research - Nonembryonic - Non-Human, Transcription, Research Article, 570, General Science & Technology, 1.1 Normal biological development and functioning, Science, 610, developmental biology, Rare Diseases, Genetic, stem cells, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Genetics, Animals, hematological malignancies, Transplantation, Neoplastic, Biomedical and Clinical Sciences, Animal, Inflammatory and immune system, Gene Expression Profiling, Stem Cell Research, Hematopoietic Stem Cells, hematopoiesis, Mice, Inbred C57BL, Disease Models, Animal, Gene Expression Regulation, Disease Models, BCR-ABL Positive, Generic health relevance, Myelogenous
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