The combination of valproic acid and lithium delays hematopoietic stem/progenitor cell differentiation
| Autor: | Albertina Ausema, Martha Ritsema, Gerald de Haan, Leonid Bystrykh, Ronald van Os, Sandra Olthof, Gerwin Huls, Vincent van den Boom, Marta A. Walasek |
|---|---|
| Přispěvatelé: | Faculteit Medische Wetenschappen/UMCG, Damage and Repair in Cancer Development and Cancer Treatment (DARE), Stem Cell Aging Leukemia and Lymphoma (SALL), Guided Treatment in Optimal Selected Cancer Patients (GUTS) |
| Jazyk: | angličtina |
| Rok vydání: | 2012 |
| Předmět: |
CHROMATIN
Time Factors Immunology FATE Drug Evaluation Preclinical Biology Cell fate determination Lithium Granulocyte-Macrophage Progenitor Cells Biochemistry Cell therapy 03 medical and health sciences Mice 0302 clinical medicine Translational research [ONCOL 3] Animals Drug Interactions Myeloid Cells Progenitor cell PLURIPOTENT Cells Cultured 030304 developmental biology Progenitor 0303 health sciences Valproic Acid PROLIFERATION Cell Differentiation IN-VITRO EXPANSION Cell Biology Hematology Hematopoietic Stem Cells GENE Cell biology Hematopoiesis Endothelial stem cell Mice Inbred C57BL SELF-RENEWAL Haematopoiesis Drug Combinations Phenotype 030220 oncology & carcinogenesis lipids (amino acids peptides and proteins) Female TRANSCRIPTION FACTOR GATA-2 Stem cell STEM-CELLS |
| Zdroj: | Blood Blood, 119(13), 3050-3059. AMER SOC HEMATOLOGY Blood; Vol 119 Blood, 119, 13, pp. 3050-9 Blood, 119, 3050-9 |
| ISSN: | 1528-0020 0006-4971 |
| DOI: | 10.1182/blood-2011-08-375386 |
| Popis: | Despite increasing knowledge on the regulation of hematopoietic stem/progenitor cell (HSPC) self-renewal and differentiation, in vitro control of stem cell fate decisions has been difficult. The ability to inhibit HSPC commitment in culture may be of benefit to cell therapy protocols. Small molecules can serve as tools to manipulate cell fate decisions. Here, we tested 2 small molecules, valproic acid (VPA) and lithium (Li), to inhibit differentiation. HSPCs exposed to VPA and Li during differentiation-inducing culture preserved an immature cell phenotype, provided radioprotection to lethally irradiated recipients, and enhanced in vivo repopulating potential. Anti-differentiation effects of VPA and Li were observed also at the level of committed progenitors, where VPA re-activated replating activity of common myeloid progenitor and granulocyte macrophage progenitor cells. Furthermore, VPA and Li synergistically preserved expression of stem cell–related genes and repressed genes involved in differentiation. Target genes were collectively co-regulated during normal hematopoietic differentiation. In addition, transcription factor networks were identified as possible primary regulators. Our results show that the combination of VPA and Li potently delays differentiation at the biologic and molecular levels and provide evidence to suggest that combinatorial screening of chemical compounds may uncover possible additive/synergistic effects to modulate stem cell fate decisions. |
| Databáze: | OpenAIRE |
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