Study: Artery Regulates Colonization of Hematopoietic Stem/Progenitor Cells in Embryonic Bone Marrow

Hematopoietic stem cells (HSCs) have been transplanted for treating malignant blood disorders after radiotherapy and chemotherapy because of their capability to differentiate into any type of specialized blood cells. The knowledge regarding the engraftment of HSCs into the bone marrow (BM) and their development is beneficial to improving transplantation efficiency. 

HSCs mainly localize in BM of adult mammalian under a steady state. The behaviors of HSCs, including their maintenance and proliferation, are affected by the BM microenvironment. The crosstalk between HSCs and the adult BM niches has been investigated in the last decade. However, the cellular and molecular mechanisms regulating the behaviors of HSCs in the embryonic BM remain unclear.  

A collaborative research has discovered the essential role of artery mediating de novo colonization of HSCs in the fetal BM. 

The work was published in Nature Communications on March 14, with CHEN Qi, principal investigator from Guangzhou Institutes of Biomedicine and Health (GIBH) of the Chinese Academy of Sciences as the co-first author. 

“We combine single cell RNA sequencing, artery-specific genetic mouse models, fluorescence activated cell sorting, imaging and transplantation experiments to investigate the initial entry of HSCs into the fetal BM.” said CHEN. 

Such approaches uncovered that the fetal BM microenvironment was fundamentally different from its adult counterpart in the aspects of cell types, gene expressions and cell-cell crosstalk. The majority of HSCs and other hematopoietic stem/progenitor cells (HSPCs) stayed closely with the BM artery at embryonic day 16.5 of mice development, suggesting that artery-derived paracrine signal regulated the status of HSCs and HSPCs. 

Furthermore, the researchers detected that a genetic blockade of Wnt secretion from the artery prevented the expansion of HSPCs. Conversely, treatment of HSPCs with Wnt2 promoted their proliferation, colony formation ability and transplantation. 

This work provides new knowledge about mechanisms regulating initial HSCs’ colonization in the fetal BM. The results may shed light on boosting HSPCs’ ability of colonization after transplantation with the analysis of fetal artery derived signal. 

“Our work also raises multiple interesting questions that deserve further investigations. For example, do HSCs determine the feature of Lepr+ stromal cells, which are absent in the fetal BM?” said CHEN. 

　　Artery guides HSC and HSPC to enter fetal bone marrow