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Nature Cover Story: HSPC “Seeds” Reveal VCAM-1+ Macrophage Role in Homing Process

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

A process called “homing” allows HSPCs to anchor in their niches in order to expand and differentiate. 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, Prof. PAN Weijun’s group at the Shanghai Institute of Nutrition and Health, of the Chinese Academy of Sciences used a zebrafish model to analyze the entire dynamic process of HSPC homing in vivo. The results entitled “VCAM-1+ macrophages guide the homing of HSPCs to a vascular niche” was published in Nature on Nov. 19, 2018 and was selected as cover story of the journal's 6 December 2018 issue. (DOI: https://doi.org/10.1038/s41586-018-0709-7)

 The cover of Nature's 6 December 2018 issue 
(Image from Nature)

By using a combination of advanced live imaging and a cell labeling-tracing system, researchers performed a high-resolution analysis of HSPC homing in zebrafish caudal hematopoietic tissue (CHT, equivalent to the fetal liver in mammals).

Compared to itga4 mutants with homing defects, successful HSPC retention was defined in CHT as the lodgement of HSPCs for more than 30 minutes.

The researchers also found that HSPCs preferred to stay at retention “hotspots” associated with venous capillaries, which are largely localized at the venous capillary confluence points connected to the caudal vein plexus.

HSPCs preferentially stayed in the retention hotspots marked by red arrows.
(Image by Prof. PanWeijun's Group)

Further study showed that VCAM-1+ macrophages patrolling the inner surface of the venous plexus interact with HSPCs in an ITGA4-dependent manner and direct HSPC retention.

These cells, named “usher cells,” guide HSCP homing to two types of vascular niches. Usher cells, together with endothelial cells, help HSPC homing through distinct mechanisms.

This study dissects the temporal-spatial rules of HSPC 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.

The study was funded by grants from the Chinese Academy of Sciences, the Ministry of Science and Technology, and the National Natural Science Foundation of China, among others.



Schematic diagrams show how usher cells guide HSPCs into their vascular niche. Magenta cells: "usher cells"; VC: venous capillary; green lines: vessels.
(Image by Prof. PAN Weijun's Group)

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