Hematopoiesis, a dynamic and well-organized process, is maintained by a rare number of multipotent cells – hematopoietic stem cells (HSCs). HSCs can not only self-renew to sustain the stability of HSC pool, but also differentiate into different types of mature blood cells.

To illustrate the whole differentiation process of HSCs, the classical hematopoietic hierarchy roadmap was proposed in 2000. Since then, the roadmap has become a dogma to define the lineage relationship between HSCs and their descendants.

Recently, with the improvement of precision and throughput of HSC study, extensive evidence demonstrates that the classical roadmap needs to be updated to describe new features of HSC differentiation.

A research team led by LIU Feng from the Institute of Zoology (IOZ) of the Chinese Academy of Sciences reported an updated hematopoietic hierarchy roadmap in a review published online in Trends in Cell Biology.

Hematopoiesis is a continuous process, which means those previously pre-defined intermediate progenitors are transitory states of continuous process. Megakaryocyte (platelet) segregation occurs early, suggesting that megakaryocytes (platelets) can be differentiated directly from HSCs. HSCs is a heterogeneous population, which is reflected in molecular signature, cell fate and functional output.

The researchers mainly focused on the above recent advances in hematopoietic hierarchy. They pinpointed that hematopoiesis underwent distinct differentiation paths under different physiological conditions, which indicated that invasive or native experimental methods would generate different hematopoietic outcomes. They also proposed future directions/applications with the updated hierarchy roadmap.

This study was supported by the National Natural Science Foundation of China, the Ministry of Science and Technology of China, and the Strategic Priority Research Program of the Chinese Academy of Sciences.

Hematopoietic hierarchy. (A) Classical hematopoietic hierarchy. HSCs undergo a stepwise differentiation process to generate different types of mature blood cells. (B) Updated hematopoietic hierarchy. HSCs produce mature blood cells passing through series of transitory states (also known as differentiation continuum). Moreover, megakaryocytes (platelets) can be differentiated directly from HSCs (blue arrow). (Image by IOZ)