| Item type |
デフォルトアイテムタイプ_（フル）(1) |
| 公開日 |
2023-03-18 |
| タイトル |
|
|
タイトル |
Single-Cell RNA-Sequencing Reveals the Breadth of Osteoblast Heterogeneity |
|
言語 |
en |
| 作成者 |
Yoshioka, Hirotaka
Okita, Saki
Nakano, Masashi
Minamizaki, Tomoko
Nubukiyo, Asako
Sotomaru, Yusuke
Bonnelye, Edith
Kozai, Katsuyuki
Tanimoto, Kotaro
Aubin, Jane E
Yoshiko, Yuji
|
| アクセス権 |
|
|
アクセス権 |
open access |
|
アクセス権URI |
http://purl.org/coar/access_right/c_abf2 |
| 権利情報 |
|
|
権利情報 |
© 2021 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research. |
| 主題 |
|
|
主題Scheme |
Other |
|
主題 |
HETEROGENEITY |
| 主題 |
|
|
主題Scheme |
Other |
|
主題 |
OSTEOBLAST |
| 主題 |
|
|
主題Scheme |
Other |
|
主題 |
RNA SEQUENCING |
| 主題 |
|
|
主題Scheme |
Other |
|
主題 |
SINGLE-CELL |
| 内容記述 |
|
|
内容記述 |
The current paradigm of osteoblast fate is that the majority undergo apoptosis, while some further differentiate into osteocytes and others flatten and cover bone surfaces as bone lining cells. Osteoblasts have been described to exhibit heterogeneous expression of a variety of osteoblast markers at both transcriptional and protein levels. To explore further this heterogeneity and its biological significance, Venus-positive (Venus+) cells expressing the fluorescent protein Venus under the control of the 2.3-kb Col1a1 promoter were isolated from newborn mouse calvariae and subjected to single-cell RNA sequencing. Functional annotation of the genes expressed in 272 Venus+ single cells indicated that Venus+ cells are osteoblasts that can be categorized into four clusters. Of these, three clusters (clusters 1 to 3) exhibited similarities in their expression of osteoblast markers, while one (cluster 4) was distinctly different. We identified a total of 1920 cluster-specific genes and pseudotime ordering analyses based on established concepts and known markers showed that clusters 1 to 3 captured osteoblasts at different maturational stages. Analysis of gene co-expression networks showed that genes involved in protein synthesis and protein trafficking between endoplasmic reticulum (ER) and Golgi are active in these clusters. However, the cells in these clusters were also defined by extensive heterogeneity of gene expression, independently of maturational stage. Cells of cluster 4 expressed Cd34 and Cxcl12 with relatively lower levels of osteoblast markers, suggesting that this cell type differs from actively bone-forming osteoblasts and retain or reacquire progenitor properties. Based on expression and machine learning analyses of the transcriptomes of individual osteoblasts, we also identified genes that may be useful as new markers of osteoblast maturational stages. Taken together, our data show much more extensive heterogeneity of osteoblasts than previously documented, with gene profiles supporting diversity of osteoblast functional activities and developmental fates. |
|
言語 |
en |
| 内容記述 |
|
|
内容記述タイプ |
Other |
|
内容記述 |
HY, SO, and YY were supported in part by the JSPS KAKENHI, Grants-in-Aid for Scientific Research (17K11613 [HY]; 18K17258 [SO]; 18K19647 [YY]). YY was also supported by the Ono Pharmaceutical Foundation. Part of this work was carried out at the Analysis Center of Life Science, Natural Science Center for Basic Research and Development, Hiroshima University. |
| 出版者 |
|
|
出版者 |
American Society for Bone and Mineral Research |
| 言語 |
|
|
言語 |
eng |
| 資源タイプ |
|
|
資源タイプ識別子 |
http://purl.org/coar/resource_type/c_6501 |
|
資源タイプ |
journal article |
| 出版タイプ |
|
|
出版タイプ |
VoR |
|
出版タイプResource |
http://purl.org/coar/version/c_970fb48d4fbd8a85 |
| 関連情報 |
|
|
|
識別子タイプ |
DOI |
|
|
関連識別子 |
10.1002/jbm4.10496 |
| 関連情報 |
|
|
|
識別子タイプ |
DOI |
|
|
関連識別子 |
https://doi.org/10.1002/jbm4.10496 |
| 収録物識別子 |
|
|
収録物識別子タイプ |
ISSN |
|
収録物識別子 |
2473-4039 |
| 開始ページ |
|
|
開始ページ |
e10496 |
| 書誌情報 |
JBMR Plus
JBMR Plus
巻 5,
号 6,
p. e10496,
発行日 2021-03-30
|
| 旧ID |
51676 |
JBMRP_5_e10496.pdf (4.7 MB)
