HSP70 regulates lipid metabolism of decidual macrophages to maintain normal pregnancy

Abstract

Dysfunction of decidual macrophages (dMs) are closely associated with recurrent pregnancy loss (RPL) which brings great suffering to patients. Metabolism is essential for regulating macrophage function. Identifying molecules that regulate metabolism and function of dMs is important to revealing the pathogenesis of RPL. Single-cell sequencing data of decidual immune cells from control and RPL patients were downloaded from the GSA database and converted into feature-barcode matrices by Cell Ranger. After quality control, removal of double cell and clustering of all cells, 3579 macrophages were extracted for normalisation, scaling and re-clustering. Function and metabolism analyses were performed by R packages AddMoudleScore, scMetabolism and AUCell. Metabolism clustering based on metabolism-related genes to clarify the metabolic characteristics of macrophages clusters. These results indicated that macrophage characterised by lipid metabolism were reduced in RPL and differential expression genes analysis found that HSP70 was significantly decreased in the RPL group. Furthermore, immunofluorescence staining demonstrated that HSP70 was significantly downregulated in dMs of RPL patients compared to controls. In conclusion, HSP70 may maintain normal pregnancy by regulating lipid metabolism of dMs. This study provides new insights into the molecular mechanisms regulating the function of dMs and provides a theoretical basis for the development of new therapies for RPL.