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Prof. Weijun Pan’s group revealed usher cells guide homing of HSPCs to a vascular niche

 

Prof. Weijun Pan’s group published a research article in Nature about the homing of Hematopoietic Stem and Progenitor Cells (HSPCs) (Dantong Li, Wenzhi Xue, Mei Li, Mei Dong, Jianwei Wang, Xianda Wang, Xiyue Li, Kai Chen, Wenjuan Zhang, Shuang Wu, Yingqi Zhang, Lei Gao, Yujie Chen, Jianfeng Chen, Bo O. Zhou, Yi Zhou, Xuebiao Yao, Lin Li, Dianqing Wu & Weijun Pan. VCAM-1+ macrophages guide the homing of HSPCs to a vascular niche. Nature 564, 119–124, December 6, 2018).)

Hematopoietic Stem and Progenitor Cells (HSPCs) give rise to all blood lineages that support people’s daily life. HSPCs, like seeds, need suitable microenvironment to maintain their function.

Homing allows the HSPCs to anchor in their niches for further expansion and differentiation. Unique niche microenvironments, composed of various blood vessels and other niche components, including stromal cells, regulate this process.

To study the detailed architecture of the microenvironment and the regulation mechanism of homing, the group at Shanghai Institute of Nutrition and Health of Chinese Academy of Sciences used zebrafish model to analyze the entire dynamic process of HSPC homing in vivo. By using a combination of advanced live imaging and cell labeling-tracing system, researchers performed a high-resolution analysis of the HSPC homing in zebrafish caudal hematopoietic tissue (CHT, equivalent to the fetal liver in mammals). Compared to itga4 mutants with homing defects, researchers defined a successful HSPC retention in the CHT as the lodgement of HSPCs for more than 30 min. They also found HSPCs preferred to stay at retention ‘hotspots’ associated with venous capillaries, which largely localized at the venous capillary confluence points that are connected to the caudal vein plexus.

Further study identified that VCAM-1+ macrophage patrolling the inner surface of venous plexus, interacts with HSPCs via an ITGA4-dependent manner, and directs HSPCs retention.

These cells, named as “Usher cells”, guide HSCPs homing to two types of vascular niche. Usher cells, together with endothelial cells, help HSPCs homing through distinct mechanisms.

Fig. Schematic diagrams show the HSPC retention model with accurate percentage and classification

This study dissects the temporal-spatial rules of HSPCs retention, provides new insights into the mechanism for HSPC homing and reveals the essential role of a VCAM-1+ macrophage population with patrolling behavior in HSPC retention.

Dantong Li, Wenzhi Xue, Mei Li, PhD students are co-first authors of the paper. Prof. Weijun Pan is the corresponding author of the study. The study was funded by grants from Chinese Academy of Sciences, Ministry of Science and Technology, National Natural Science Foundation of China, etc.