Stress Hematopoiesis Is Regulated by the Krüppel-Like Transcription Factor ZBP-89
Copyright policy )Stress Hematopoiesis Is Regulated by the Krüppel-Like Transcription Factor ZBP-89
Abstract Previous studies have shown that ZBP-89 (Zfp148) plays a critical role in erythroid lineage development, with its loss at the embryonic stage causing lethal anemia and thrombocytopenia. Its role in adult hematopoiesis has not been described. We now show that conditional deletion of ZBP-89 in adult mouse hematopoietic stem/progenitor cells (HSPC) causes anemia and thrombocytopenia that are transient in the steady state, but readily uncovered following chemically induced erythro/megakaryopoietic stress. Unexpectedly, stress induced by bone marrow transplantation of ZBP89−/− HSPC also resulted in a myeloid-to-B lymphoid lineage switch in bone marrow recipients. The erythroid and myeloid/B lymphoid lineage anomalies in ZBP89−/− HSPC are reproduced in vitro in the ZBP-89-silenced multipotent hematopoietic cell line FDCP-Mix A4, and are associated with the upregulation of PU.1 and downregulation of SCL/Tal1 and GATA-1 in ZBP89-deficient cells. Chromatin immunoprecipitation and luciferase reporter assays show that ZBP-89 is a direct repressor of PU.1 and activator of SCL/Tal1 and GATA-1. These data identify an important role for ZBP-89 in regulating stress hematopoiesis in adult mouse bone marrow. Stem Cells 2014;32:791–801
- Harvard University United States
- Massachusetts General Hospital United States
- University of Michigan–Flint United States
- Harvard Stem Cell Institute, Cambridge, MA, USA United States
- University of Michigan United States
Aging, Cell Count, Stress Hematopoiesis, Immunophenotyping, Mice, Bone Marrow, Cell Line, Tumor, Health Sciences, Basic Helix-Loop-Helix Transcription Factors, Animals, Cell Lineage, Erythropoiesis, GATA1 Transcription Factor, Gene Silencing, Cellular and Developmental Biology, Transplantation, B-Lymphocytes, Base Sequence, Molecular, Anemia, Hematopoietic Stem Cells, Hematopoiesis, DNA-Binding Proteins, Erythroid Progenitors, Gene Expression Regulation, Gene Deletion, Transcription Factors
Aging, Cell Count, Stress Hematopoiesis, Immunophenotyping, Mice, Bone Marrow, Cell Line, Tumor, Health Sciences, Basic Helix-Loop-Helix Transcription Factors, Animals, Cell Lineage, Erythropoiesis, GATA1 Transcription Factor, Gene Silencing, Cellular and Developmental Biology, Transplantation, B-Lymphocytes, Base Sequence, Molecular, Anemia, Hematopoietic Stem Cells, Hematopoiesis, DNA-Binding Proteins, Erythroid Progenitors, Gene Expression Regulation, Gene Deletion, Transcription Factors
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