Kidney Week

Abstract: FR-PO094

Single-Cell Deconvolution of Macrophage Heterogeneity in Mouse Ischemia-Reperfusion Kidney Injury

Session Information

• AKI: Mechanisms - Inflammation/Sepsis/Remote Injury
  November 08, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Acute Kidney Injury

• 103 AKI: Mechanisms

Authors

• Yao, Weijian, Renal Division, Peking University First Hospital, Beijing, China

Weijian Yao,

• Jin, Shanzhao, Biomedical Pioneering Innovation Center (BIOPIC) ,School of Life Sciences, Peking University, Beijing, China

Shanzhao Jin,

• Li, Zehua, Renal Division, Peking University First Hospital, Beijing, China

Zehua Li,

• Bai, Fan, Biomedical Pioneering Innovation Center (BIOPIC) ,School of Life Sciences, Peking University, Beijing, China

Fan Bai,

• Yang, Li, Renal Division, Peking University First Hospital, Beijing, China

Li Yang,

Background

Acute kidney injury (AKI) is a clinically critical illness without effective treatment.It has been known that macrophage plays important roles in the repair and fibrosis after acute injury,whereas its heterogeneity in subtypes and the related pathophysiological functions during the progression of AKI have not been well established.

Methods

Unilateral ischemia reperfusion (uIRI) acute kidney injury model was set up in C57BL/6J male mice (37°C for 45minutes).Macrophages were collected from the injured kidney on day 1, 3,10,17 post surgery by flowcytometry cell sorting through costainting with F4/80 and Cd11b.Meanwhile,monocytes costaining with Ly6c and Cd11b were sorted from peripheral blood and spleen respectively.Single cell transcriptome sequencing was performed through 10X genomics method.

Results

Altogether eleven clusters of macrophages were discovered in the kidney.There were three subclusters of kidney resident macrophages in normal kidney and they almost disappeared after injury.On day 1 post uIRI surgery,S100a4^highand S100a8^highmacrophage took the majority of macrophage subtypes in the kidney,while Stmn1^highmacrophage was the major populations on day 3,which had a strong ability of proliferation.Cxcl2^highmacrophage and Gdf15^highmacrophage mainly existed in the chronic phase (day 17).According to Gene Oncology analysis,Cxcl2^highmacrophage exhibited inflammatory response and TNF signaling pathway activation,while Gdf15^highmacrophage had more repair related genes and thus might promote repair after injury.Through single-cell trajectory analysis on integrated datas,MHC-II^-Gpx3^highkidney resident macrophage developed into S100a4^highmacrophage through Stmn1^highmacrophage and S100a8^highmacrophage mainly derived from spleen in the acute phase.In the chronic phase,MHC-II⁺MMP13^highand MHC-II^- F13a1^highkidney resident macrophage developed into Cxcl2^high macrophage while Stmn1^highmacrophage proliferate and different into Hspa1a^highmacrophage and Gdf15^highmacrophage.

Conclusion

Macrophages have strong heterogeneity in AKI.S100a4^highand S100a8^highmacrophages might contribute to inflammation during acute injury phase.Gdf15^highmacrophage was likely to promote repair,while Cxcl2^highmacrophage could be involved in the chronic inflammation and fibrosis processes.Kidney resident macrophages and monocytes derived from spleen might play important role in AKI.

Funding

• Government Support - Non-U.S.