Bibliographic Details
| Title: |
Next-generation proteomics of serum extracellular vesicles combined with single-cell RNA sequencing identifies MACROH2A1 associated with refractory COVID-19 |
| Authors: |
Takahiro Kawasaki, Yoshito Takeda, Ryuya Edahiro, Yuya Shirai, Mari Nogami-Itoh, Takanori Matsuki, Hiroshi Kida, Takatoshi Enomoto, Reina Hara, Yoshimi Noda, Yuichi Adachi, Takayuki Niitsu, Saori Amiya, Yuta Yamaguchi, Teruaki Murakami, Yasuhiro Kato, Takayoshi Morita, Hanako Yoshimura, Makoto Yamamoto, Daisuke Nakatsubo, Kotaro Miyake, Takayuki Shiroyama, Haruhiko Hirata, Jun Adachi, Yukinori Okada, Atsushi Kumanogoh |
| Source: |
Inflammation and Regeneration, Vol 42, Iss 1, Pp 1-19 (2022) |
| Publisher Information: |
BMC, 2022. |
| Publication Year: |
2022 |
| Collection: |
LCC:Pathology |
| Subject Terms: |
COVID-19, SARS-CoV-2, Exosome, MACROH2A1, Multi-omics, Liquid biopsy, Pathology, RB1-214 |
| More Details: |
Abstract Background The coronavirus disease 2019 (COVID-19) pandemic is widespread; however, accurate predictors of refractory cases have not yet been established. Circulating extracellular vesicles, involved in many pathological processes, are ideal resources for biomarker exploration. Methods To identify potential serum biomarkers and examine the proteins associated with the pathogenesis of refractory COVID-19, we conducted high-coverage proteomics on serum extracellular vesicles collected from 12 patients with COVID-19 at different disease severity levels and 4 healthy controls. Furthermore, single-cell RNA sequencing of peripheral blood mononuclear cells collected from 10 patients with COVID-19 and 5 healthy controls was performed. Results Among the 3046 extracellular vesicle proteins that were identified, expression of MACROH2A1 was significantly elevated in refractory cases compared to non-refractory cases; moreover, its expression was increased according to disease severity. In single-cell RNA sequencing of peripheral blood mononuclear cells, the expression of MACROH2A1 was localized to monocytes and elevated in critical cases. Consistently, single-nucleus RNA sequencing of lung tissues revealed that MACROH2A1 was highly expressed in monocytes and macrophages and was significantly elevated in fatal COVID-19. Moreover, molecular network analysis showed that pathways such as “estrogen signaling pathway,” “p160 steroid receptor coactivator (SRC) signaling pathway,” and “transcriptional regulation by STAT” were enriched in the transcriptome of monocytes in the peripheral blood mononuclear cells and lungs, and they were also commonly enriched in extracellular vesicle proteomics. Conclusions Our findings highlight that MACROH2A1 in extracellular vesicles is a potential biomarker of refractory COVID-19 and may reflect the pathogenesis of COVID-19 in monocytes. |
| Document Type: |
article |
| File Description: |
electronic resource |
| Language: |
English |
| ISSN: |
1880-8190 |
| Relation: |
https://doaj.org/toc/1880-8190 |
| DOI: |
10.1186/s41232-022-00243-5 |
| Access URL: |
https://doaj.org/article/77f6618fb474472ab013b5ae1a42c451 |
| Accession Number: |
edsdoj.77f6618fb474472ab013b5ae1a42c451 |
| Database: |
Directory of Open Access Journals |
