Analysis on cellular fate decision of mesenchymal cells during bone and bone marrow development

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K08417
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 54010:Hematology and medical oncology-related
• Research Institution: The University of Tokyo (2022-2023); Kyushu University (2021)
• Principal Investigator: Sumiya Eriko 東京大学, 医学部附属病院, 特別研究員 (50724754)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 骨髄ストローマ細胞 / 骨髄発生 / RANKL

Outline of Final Research Achievements

Bone marrow is the major hematopoietic tissue in postnatal mammalian animals. Bone marrow is known to be formed along with bone development. However, the origin and cellular lineage of bone marrow-composing cells have not been fully elucidated. In the present study, cellular lineages of murine embryonic mesenchymal cells of the bone and bone marrow were analyzed. A portion of mesenchymal cells in the early bone marrow were found to be already committed to osteoblastic or bone marrow stromal lineages, and these nascent cells further matured as the developmental stage proceeded. Furthermore, fetal septoclasts were identified at the chondro-osseous junction of the developing bone marrow. Altogether this study provides new insights into the cellular populations which participate in the development of early hematopoietic tissue.

Free Research Field

骨発生学

Academic Significance and Societal Importance of the Research Achievements

抗がん剤による化学療法に伴う骨髄抑制や、加齢による造血機能の低下に起因する貧血などに対して骨髄機能を賦活化する治療法の開発が必要とされている。機能的な骨髄の再建には、造血幹細胞の移植のみならず、同時にそれ支持する微小環境を再構築することの重要性が指摘されているが、その方法は確立されていない。本研究によって発生期の幼若骨髄を構成する細胞群の由来や性状の一端が明らかとなり、生体にプログラムされた造血環境の構築メカニズムに対する理解が進んだという学術的な意義に加え、同定した幼若細胞群に関する知見は将来的には人工的に骨髄を再建する技術の開発に資する可能性がある。