Novel Roles for the Homeobox Gene, HoxA1, and Its Truncated Form, HoxA1-T, in the Regulation of Hematopoietic Stem Cell Self-Renewal

التفاصيل البيبلوغرافية
العنوان: Novel Roles for the Homeobox Gene, HoxA1, and Its Truncated Form, HoxA1-T, in the Regulation of Hematopoietic Stem Cell Self-Renewal
المؤلفون: Paul J. Simmons, Louise E. Purton, Seb Dworkin, Stewart A. Fabb, Gemma Haines, Lorraine J. Gudas
المصدر: Blood. 104:1706-1706
بيانات النشر: American Society of Hematology, 2004.
سنة النشر: 2004
مصطلحات موضوعية: Immunology, Hematopoietic stem cell, Cell Biology, Hematology, Biology, Biochemistry, Molecular biology, Green fluorescent protein, Haematopoiesis, medicine.anatomical_structure, medicine, Homeobox, Progenitor cell, Stem cell, Hox gene, Gene
الوصف: There is increasing evidence that homeobox (Hox) genes play critical roles in the regulation of hematopoiesis. We found that both forms of the earliest HoxA gene, HoxA1 and its alternatively spliced transcript, HoxA1-T, which lacks the homeobox domain, are expressed in immature populations of hematopoietic stem cells (HSCs) and progenitor cells. In more mature bone marrow cell (BM) populations the levels of HoxA1-T increases relative to HoxA1 with both transcripts absent in mature peripheral blood (PB) cells. Roles for either of these Hox transcripts in hematopoiesis have not yet been described. We overexpressed either HoxA1 or HoxA1-T in BM using a modified GFP-containing MSCV vector (MXIE). Overexpression of either HoxA1 transcript did not affect expression levels of other Hox genes relative to control (empty vector). Overexpression of HoxA1-T significantly reduced the numbers of colony-forming cells (CFCs) produced by 500 GFP+ BM compared to control GFP+ BM (mean±SEM control 73±6.4; HoxA1 57±6.8; HoxA1-T 26.7±5.4; n=6; P75% donor cells (CD45.1+, GFP+/−) in their PB at 3 months post-transplant. The average %GFP+ cells in recipients were similar for control (24.5±7.0%) and HoxA1 cells (20.8±2.5%). Strikingly, HSCs overexpressing HoxA1-T had markedly reduced repopulating ability (3.5±0.6% GFP+, P
تدمد: 1528-0020
0006-4971
URL الوصول: https://explore.openaire.eu/search/publication?articleId=doi_________::4c22ddaf6413fc1ce78568dac0a4c2e8
https://doi.org/10.1182/blood.v104.11.1706.1706
رقم الأكسشن: edsair.doi...........4c22ddaf6413fc1ce78568dac0a4c2e8
قاعدة البيانات: OpenAIRE