Academic Journal
Bone morphogenetic protein 4 differently promotes distinct VE-cadherin+ precursor stages during the definitive hematopoietic development from embryonic stem cell-derived mesodermal cells
العنوان: | Bone morphogenetic protein 4 differently promotes distinct VE-cadherin+ precursor stages during the definitive hematopoietic development from embryonic stem cell-derived mesodermal cells |
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المؤلفون: | 鶴田 真理子, 古賀 沙緒里, 小川 峰太郎, Mariko Tsuruda, Saori Morino-Koga, Minetaro Ogawa |
بيانات النشر: | International Society for Experimental Hematology |
سنة النشر: | 2021 |
المجموعة: | Kumamoto University Repository |
مصطلحات موضوعية: | Bone Morphogenetic Protein 4, VE-cadherin, Mouse Embryonic Stem Cells, Mesoderm, Hemogenic Endothelial Cells, Stromal Cells |
الوصف: | Definitive hematopoietic cells develop from the fetal liver kinase 1 (Flk1)+ mesodermal cells during the in vitro differentiation of mouse embryonic stem cells (ESCs). VE-cadherin+CD41-CD45- (V+41-45-) hemogenic endothelial cells (HECs) and VE-cadherin+CD41+CD45- (V+41+45-) cells mediate the definitive hematopoietic development from Flk1+ cells. Bone morphogenetic protein 4 (BMP4) is known to be essential for the formation of mesoderm. However, the role of BMP4 in the differentiation of the VE-cadherin+ definitive hematopoietic precursors from the mesoderm has been elusive. We addressed this issue using a co-aggregation culture of ESC-derived Flk1+ cells with OP9 stromal cells. This culture method induced V+41-45- cells, V+41+45- cells, and CD45+ cells from Flk1+ cells. V+41+45- cells possessed the potentials of erythromyeloid and T-lymphoid differentiation. When Flk1+ cells were cultured in the presence of a high concentration of BMP4, the generation of V+41-45- cells was enhanced. The increase of V+41-45- cells led to the subsequent increase of V+41+45- cells and CD45+ cells. The addition of BMP4 also increased hematopoietic colony-forming cells of various lineages. Furthermore, BMP4 promoted the expansion of V+41+45- cells independently of the preceding V+41-45- cell stage. These results suggest that BMP4 has promotive effects on the differentiation of V+41-45- HECs from Flk1+ mesodermal cells and the subsequent proliferation of V+41+45- hematopoietic precursors. These findings may provide insights for establishing a culture system to induce definitive hematopoietic stem cells from ESCs. |
نوع الوثيقة: | article in journal/newspaper |
اللغة: | English |
تدمد: | 0301-472X |
Relation: | https://kumadai.repo.nii.ac.jp/?action=repository_uri&item_id=34530; http://hdl.handle.net/2298/00045963; Experimental hematology, 103, 40-50.e7(2021-11-18); https://kumadai.repo.nii.ac.jp/?action=repository_action_common_download&item_id=34530&item_no=1&attribute_id=21&file_no=1 |
الاتاحة: | http://hdl.handle.net/2298/00045963 https://kumadai.repo.nii.ac.jp/?action=repository_uri&item_id=34530 https://kumadai.repo.nii.ac.jp/?action=repository_action_common_download&item_id=34530&item_no=1&attribute_id=21&file_no=1 |
Rights: | (C)2021 ISEH - Society for Hematology and Stem Cells.This manuscript version is made available under the CC-BY-NC-ND 4.0 License. http://creativecommons.org/licenses/by-nc-nd/4.0/. ; This is the accepted manuscript version. The formal published version is available at https://doi.org/10.1016/j.exphem.2021.08.008. |
رقم الانضمام: | edsbas.43BE6B2D |
قاعدة البيانات: | BASE |
تدمد: | 0301472X |
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