Hmgb3: an HMG-box family member expressed in primitive hematopoietic cells that inhibits myeloid and B-cell differentiation
Autor: | Nancy E. Seidel, David J. Curtis, David M. Bodine, Michael J. Nemeth, Martha Kirby, Amanda P. Cline, Lisa Garrett-Beal |
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Rok vydání: | 2003 |
Předmět: |
Male
DNA Complementary Myeloid Cellular differentiation Genetic Vectors Immunology Down-Regulation Mice Transgenic Biology Biochemistry Mice HMGB3 Protein medicine Animals RNA Messenger Lymphopoiesis Myeloid Progenitor Cells Interleukin 3 B-Lymphocytes Stem Cell Factor Gene Transfer Techniques Bone Marrow Stem Cell Cell Differentiation Cell Biology Hematology Hematopoietic Stem Cells Molecular biology Hematopoiesis Mice Inbred C57BL Haematopoiesis Retroviridae medicine.anatomical_structure Bone marrow Stem cell |
Zdroj: | Blood. 102:1298-1306 |
ISSN: | 1528-0020 0006-4971 |
Popis: | Hmgb3 is a member of a family of chromatin-binding proteins that can alter DNA structure to facilitate transcription factor binding. We identified the Hmgb3 cDNA in a subtractive hybridization screen for transcripts that are preferentially expressed in hematopoietic stem cells. We inserted an internal ribosomal entry site–green fluorescence protein cassette into the 3′ untranslated region of the X-linked Hmgb3 locus to identify Hmgb3-expressing cells. In adult mice, Hmgb3 mRNA is detected in bone marrow cells, primitive Lin–, c-kit+, Sca-1+, IL-7Rα– cells, and Ter119+ erythroid cells. We observed that long-term repopulating ability is entirely contained in the subpopulation of Lin–, c-kitHI cells that express Hmgb3. Most common lymphoid and myeloid progenitors express Hmgb3. Introduction of a retrovirus containing the Hmgb3 cDNA into mouse bone marrow stem cells demonstrated that enforced expression of Hmgb3 inhibited B-cell and myeloid differentiation. We conclude that down-regulation of Hmgb3 protein levels is an important step for myeloid and B-cell differentiation. |
Databáze: | OpenAIRE |
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