Capability of relatively mature osteoblasts to shift bone forming osteoblasts

• Project/Area Number: 18K17258
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 57070:Developmental dentistry-related
• Research Institution: Hiroshima University
• Principal Investigator: Okita Saki 広島大学, 医系科学研究科(歯), 研究員 (20806674)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2020: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 骨芽細胞 / シングルセルRNA-Seq / 骨芽細胞の多様性 / 骨代謝

Outline of Final Research Achievements

Single-cell RNA-sequencing analysis was carried out in Venus-positive (Venus+) osteoblasts isolated from mice expressing the fluorescent protein Venus under the control of the 2.3kb Col1a1 promoter. Two hundred seventy-two Venus+ osteoblasts can be categorized into four clusters. Of these, one cluster uniquely expressed stem cell markers such as Cd34 (Cd34+ cluster) was focused , because cells in this cluster also expressed some of mature osteoblast marker genes relatively abundantly. Pseudotime ordering analyses showed that cells in the Cd34+ cluster were not distributed in the osteoblast differentiation lineage. These results suggest that a part of osteoblasts may have additional traits involved in bone metabolism.

Academic Significance and Societal Importance of the Research Achievements

骨芽細胞の多様性のメカニズムは，ほとんど解明されていない。これまでに我々は成熟骨芽細胞の一部に骨原生マーカー (Cd34) を発現する細胞集団を確認し，今回はこの細胞集団に着目して解析を進めた。その結果，Cd34+骨芽細胞は未分化な細胞ではなく，特殊な細胞集団であることが推察された。また，これまでに骨芽細胞において機能が明らかにされていない遺伝子が複数リストアップされた。これらはCd34+骨芽細胞の性質を理解する上で重要であると考えられる。本課題の期間内にそれらの機能解析には至らなかったものの，骨芽細胞の多様性のメカニズムを解明する足掛かりになったと考える。

Research Products

• [Journal Article] Single‐cell RNA‐sequencing reveals the breadth of osteoblast heterogeneity (2021)
  • Author(s): Yoshioka H, Okita S, Nakano M, Minamizaki T, Nubukiyo A, Sotomaru Y, Bonnelye E, Kozai K, Tanimoto K, Aubin JE, Yoshiko Y
  • Journal Title: JBMR Plus Volume: - Issue: 6
  • DOI: 10.1002/jbm4.10496
  • NAID: 120007183697
  • Peer Reviewed / Open Access / Int'l Joint Research