Mesenchymal stem cell treatment restores liver macrophages homeostasis to alleviate mouse acute liver injury revealed by single-cell analysis
Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved..
Acute liver injury (ALI) is characterized by massive hepatocyte necrosis and subsequent recruitment of myeloid cells to liver. Mesenchymal stem cells (MSCs) have therapeutic potential for ALI through their immunoregulation on macrophages, but the mechanism is not completely clear due to the heterogeneity and controversy of liver macrophages. Here, we detected the survival rate, biochemical indexes, histopathology, and inflammatory chemokine levels to assess the efficacy of MSC treatment on CCl4-induced ALI of C57BL/6 mice. Furthermore, flow cytometry and single-cell RNA sequencing (scRNA-Seq) were used to precisely distinguish macrophage populations and reveal the immunoregulation of MSCs. MSC treatment could effectively alleviate ALI and mitigate the recruitment of mononuclear phagocytes. Flow cytometry and scRNA-Seq analyses collectively indicated that there were monocytes with high Ly6C expression and heterogeneous monocyte-derived macrophages (MoMF) with low Ly6C expression in liver. Ly6Chi pro-inflammatory monocytes and Ly6Clo MoMF with powerful phagocytosis dominated during the acute injury period. MSC treatment promoted the transition from Ly6Chi to Ly6Clo population, inhibit the proinflammatory function of monocytes and promote the lysosomal function of MoMF. Furthermore, MSCs attenuated the recruitment of neutrophils by reducing the expression of CXCL2 of MoMF. MoMF with high expression of arginase 1 appeared during the recovery period, and MSCs could increase their expression of arginase 1, which may promote liver repair. To sum up, we demonstrated the characteristics of distinct MoMF during different periods of ALI and revealed their functional changes after MSC treatment, providing immunotherapeutic targets for MSC treatment of ALI.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2022 |
|---|---|
| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:179 |
|---|---|
| Enthalten in: |
Pharmacological research - 179(2022) vom: 20. Mai, Seite 106229 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Zhou, Jiahang [VerfasserIn] |
|---|
| Links: |
|---|
| Anmerkungen: |
Date Completed 24.05.2022 Date Revised 07.06.2022 published: Print-Electronic Citation Status MEDLINE |
|---|
| doi: |
10.1016/j.phrs.2022.106229 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM339991194 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM339991194 | ||
| 003 | DE-627 | ||
| 005 | 20231226004134.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231226s2022 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1016/j.phrs.2022.106229 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1133.xml |
| 035 | |a (DE-627)NLM339991194 | ||
| 035 | |a (NLM)35470065 | ||
| 035 | |a (PII)S1043-6618(22)00174-8 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Zhou, Jiahang |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Mesenchymal stem cell treatment restores liver macrophages homeostasis to alleviate mouse acute liver injury revealed by single-cell analysis |
| 264 | 1 | |c 2022 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 24.05.2022 | ||
| 500 | |a Date Revised 07.06.2022 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved. | ||
| 520 | |a Acute liver injury (ALI) is characterized by massive hepatocyte necrosis and subsequent recruitment of myeloid cells to liver. Mesenchymal stem cells (MSCs) have therapeutic potential for ALI through their immunoregulation on macrophages, but the mechanism is not completely clear due to the heterogeneity and controversy of liver macrophages. Here, we detected the survival rate, biochemical indexes, histopathology, and inflammatory chemokine levels to assess the efficacy of MSC treatment on CCl4-induced ALI of C57BL/6 mice. Furthermore, flow cytometry and single-cell RNA sequencing (scRNA-Seq) were used to precisely distinguish macrophage populations and reveal the immunoregulation of MSCs. MSC treatment could effectively alleviate ALI and mitigate the recruitment of mononuclear phagocytes. Flow cytometry and scRNA-Seq analyses collectively indicated that there were monocytes with high Ly6C expression and heterogeneous monocyte-derived macrophages (MoMF) with low Ly6C expression in liver. Ly6Chi pro-inflammatory monocytes and Ly6Clo MoMF with powerful phagocytosis dominated during the acute injury period. MSC treatment promoted the transition from Ly6Chi to Ly6Clo population, inhibit the proinflammatory function of monocytes and promote the lysosomal function of MoMF. Furthermore, MSCs attenuated the recruitment of neutrophils by reducing the expression of CXCL2 of MoMF. MoMF with high expression of arginase 1 appeared during the recovery period, and MSCs could increase their expression of arginase 1, which may promote liver repair. To sum up, we demonstrated the characteristics of distinct MoMF during different periods of ALI and revealed their functional changes after MSC treatment, providing immunotherapeutic targets for MSC treatment of ALI | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a 4', 6-Diamidino-2-phenylindole (PubChem CID: 2954) | |
| 650 | 4 | |a Acute liver injury | |
| 650 | 4 | |a Carbon tetrachloride (PubChem CID: 5943) | |
| 650 | 4 | |a Dimethyl sulfoxide (PubChem CID: 679) | |
| 650 | 4 | |a Mesenchymal stem cells | |
| 650 | 4 | |a Monocyte | |
| 650 | 4 | |a Monocyte-derived macrophages | |
| 650 | 4 | |a Single-cell RNA sequencing | |
| 650 | 7 | |a Arginase |2 NLM | |
| 650 | 7 | |a EC 3.5.3.1 |2 NLM | |
| 700 | 1 | |a Feng, Xudong |e verfasserin |4 aut | |
| 700 | 1 | |a Zhu, Jiaqi |e verfasserin |4 aut | |
| 700 | 1 | |a Feng, Bing |e verfasserin |4 aut | |
| 700 | 1 | |a Yao, Qigu |e verfasserin |4 aut | |
| 700 | 1 | |a Pan, Qiaoling |e verfasserin |4 aut | |
| 700 | 1 | |a Yu, Jiong |e verfasserin |4 aut | |
| 700 | 1 | |a Yang, Jinfeng |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Lanjuan |e verfasserin |4 aut | |
| 700 | 1 | |a Cao, Hongcui |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Pharmacological research |d 1992 |g 179(2022) vom: 20. Mai, Seite 106229 |w (DE-627)NLM012597384 |x 1096-1186 |7 nnns |
| 773 | 1 | 8 | |g volume:179 |g year:2022 |g day:20 |g month:05 |g pages:106229 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1016/j.phrs.2022.106229 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 179 |j 2022 |b 20 |c 05 |h 106229 | ||