Expression of Pitx2 in stromal cells is required for normal hematopoiesis
| Autor: | Bernard G. Forget, Nicole Navarro, Anne Dubart-Kupperschmitt, Georges Uzan, Brigitte Izac, Philip J. Gage, Cécile Kerdudo, Aurélie Kieusseian, Philippe E. Mangeot, Jalila Chagraoui |
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| Přispěvatelé: | Garcia, Marie, Institut Cochin (UMR_S567 / UMR 8104), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Human Genetics, University of Michigan [Ann Arbor], University of Michigan System-University of Michigan System, Medicine/Genetics, Yale School of Medicine [New Haven, Connecticut] (YSM), Ontogenese de l'Hematopoiese, Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5), Yale University School of Medicine, Université Paris Descartes - Paris 5 (UPD5) - Institut National de la Santé et de la Recherche Médicale (INSERM) - Centre National de la Recherche Scientifique (CNRS), Yale School of Medicine, Université Paris-Sud - Paris 11 (UP11) - Institut National de la Santé et de la Recherche Médicale (INSERM) |
| Jazyk: | angličtina |
| Rok vydání: | 2006 |
| Předmět: |
[SDV.BIO]Life Sciences [q-bio]/Biotechnology
MESH : Transcription Factors MESH: Hematopoiesis MESH : RNA Small Interfering Biochemistry MESH: Mice Knockout Mice 0302 clinical medicine MESH: RNA Small Interfering MESH: Gene Expression Regulation Developmental MESH: Animals MESH : Homeodomain Proteins RNA Small Interfering [INFO.INFO-BT]Computer Science [cs]/Biotechnology Cells Cultured MESH: Lentivirus Mice Knockout 0303 health sciences PITX2 Stem Cells Homozygote Gene Expression Regulation Developmental Nuclear Proteins Hematology MESH: Transcription Factors MESH : Fetus Cell biology Haematopoiesis medicine.anatomical_structure MESH : Lentivirus Liver 030220 oncology & carcinogenesis MESH : Stem Cells MESH : Transfection MESH : Colony-Forming Units Assay MESH: Cells Cultured MESH: Homozygote congenital hereditary and neonatal diseases and abnormalities Stromal cell Ratón Immunology MESH : Mice Inbred C57BL MESH: Stem Cells Biology Transfection Colony-Forming Units Assay 03 medical and health sciences Fetus MESH : Homozygote stomatognathic system MESH: Mice Inbred C57BL MESH : Cells Cultured MESH : Mice MESH: Homeodomain Proteins Lymph node stromal cell medicine Animals MESH: Colony-Forming Units Assay Progenitor cell MESH: Mice 030304 developmental biology Homeodomain Proteins MESH: Transfection Lentivirus MESH : Nuclear Proteins MESH : Liver MESH: Fetus Cell Biology Hematopoiesis [SDV.BIO] Life Sciences [q-bio]/Biotechnology Mice Inbred C57BL MESH : Hematopoiesis stomatognathic diseases [INFO.INFO-BT] Computer Science [cs]/Biotechnology MESH : Stromal Cells MESH : Mice Knockout Bone marrow MESH : Animals MESH : Gene Expression Regulation Developmental sense organs Stromal Cells MESH: Stromal Cells MESH: Nuclear Proteins Transcription Factors MESH: Liver |
| Zdroj: | Blood Blood, 2006, 107 (2), pp.492-500. ⟨10.1182/blood-2005-02-0529⟩ Blood, American Society of Hematology, 2006, 107 (2), pp.492-500. ⟨10.1182/blood-2005-02-0529⟩ Blood, American Society of Hematology, 2006, 107 (2), pp.492-500. 〈10.1182/blood-2005-02-0529〉 |
| ISSN: | 0006-4971 1528-0020 |
| DOI: | 10.1182/blood-2005-02-0529⟩ |
| Popis: | Although the expression of Pitx2, a bicoid family homeodomain transcription factor, is highly regulated during hematopoiesis, its function during this process was not documented; we thus studied hematopoiesis in Pitx2-null mice. We found that Pitx2–/– embryos display hypoplastic livers with reduced numbers of hematopoietic cells, but these cells had normal hematopoietic potential, as evidenced by colony-forming assays, immature progenitor cell assays, and long-term repopulation assays. Because the microenvironment is also crucial to the development of normal hematopoiesis, we established Pitx2–/– and Pitx2+/+ stromas from fetal liver and studied their hematopoietic supportive capacity. We showed that the frequency of cobblestone area-forming cells was 4-fold decreased when using Pitx2–/– stromal cells compared with Pitx2+/+ stromal cells, whatever the Pitx2 genotype of hematopoietic cells tested in this assay. This defect was rescued by expression of Pitx2 into Pitx2–/– fetal liver stromal cells, demonstrating a major and direct role of Pitx2 in the hematopoietic supportive capacity of fetal liver stroma. Finally, we showed a reduced capacity of MS5 stromal cells expressing Pitx2 RNAi to support human hematopoiesis. Altogether these data showed that Pitx2 has major functions in the hematopoietic supportive capacity of fetal liver and adult bone marrow stromal cells. |
| Databáze: | OpenAIRE |
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