Single-cell RNA sequencing-guided fate-mapping toolkit delineates the contribution of yolk sac erythro-myeloid progenitors
Y.X. Zhao,
J.Y. Song,
X.W. Bao,
J.L. Zhang,
J.C. Wu,
L.Y. Wang,
C. He,
W. Shao,
X.L. Bai,
T.B. Liang,
J.P. Sheng
Affiliations
Y.X. Zhao
Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310002, China; Zhejiang Provincial Key Laboratory of Pancreatic Disease, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310002, China; Zhejiang University Cancer Center, Zhejiang University, Hangzhou 310002, China
J.Y. Song
Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310002, China; Zhejiang Provincial Key Laboratory of Pancreatic Disease, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310002, China; Zhejiang University Cancer Center, Zhejiang University, Hangzhou 310002, China
X.W. Bao
Department of Medical Oncology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310002, China
J.L. Zhang
Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310002, China; Zhejiang Provincial Key Laboratory of Pancreatic Disease, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310002, China; Zhejiang University Cancer Center, Zhejiang University, Hangzhou 310002, China
J.C. Wu
Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310002, China; Zhejiang Provincial Key Laboratory of Pancreatic Disease, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310002, China; Zhejiang University Cancer Center, Zhejiang University, Hangzhou 310002, China
L.Y. Wang
Eye Center, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, Zhejiang, China
C. He
Infinity Scope Biotechnology Co., Ltd., Hangzhou 311200, China
W. Shao
College of Computer Science and Technology, Nanjing University of Aeronautics and Astronautics, Nanjing 210000, China; Corresponding author
X.L. Bai
Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310002, China; Zhejiang Provincial Key Laboratory of Pancreatic Disease, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310002, China; Zhejiang University Cancer Center, Zhejiang University, Hangzhou 310002, China; Corresponding author
T.B. Liang
Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310002, China; Zhejiang Provincial Key Laboratory of Pancreatic Disease, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310002, China; Zhejiang University Cancer Center, Zhejiang University, Hangzhou 310002, China; Corresponding author
J.P. Sheng
Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310002, China; Zhejiang Provincial Key Laboratory of Pancreatic Disease, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310002, China; Zhejiang University Cancer Center, Zhejiang University, Hangzhou 310002, China; Corresponding author
Summary: Erythro-myeloid progenitors of the yolk sac that originates during early embryo development has been suggested to generate tissue-resident macrophage, mast cell, and even endothelial cell populations from fetal to adult stages. However, the heterogeneity of erythro-myeloid progenitors (EMPs) is not well characterized. Here, we adapt single-cell RNA sequencing to dissect the heterogeneity of EMPs and establish several fate-mapping tools for each EMP subset to trace the contributions of different EMP subsets. We identify two primitive and one definitive EMP subsets from the yolk sac. In addition, we find that primitive EMPs are decoupled from definitive EMPs. Furthermore, we confirm that primitive and definitive EMPs give rise to microglia and other tissue-resident macrophages, respectively. In contrast, only Kit+ Csf1r− primitive EMPs generate endothelial cells transiently during early embryo development. Overall, our results delineate the contribution of yolk sac EMPs more clearly based on the single-cell RNA sequencing (scRNA-seq)-guided fate-mapping toolkit.
