Unexpected role of inflammatory signaling in hematopoietic stem cell development: its role beyond inflammation

Inflammatory signaling under pathological conditions like infection and inflammation has been extensively studied. Whether inflammatory signaling plays a role in physiology and development remains elusive. The review summarizes recent advances in inflammatory signaling with particular focus on how distinct inflammatory signaling regulates hematopoietic stem cell (HSC) development. Understanding the underlying mechanism of inflammatory signaling on HSC development may help to generate and/or expand a large number of functional HSCs for clinical application.

Like the hematopoietic progenitors, HSCs can be the first responders to infection. An unexpected observation is that genes involved in innate immunity and inflammatory signaling are enriched in emerging HSCs and their niche during embryogenesis. Thus, inflammatory signaling may also play a role in HSC development in the absence of infection and inflammation.

Inflammatory signaling is not only an important regulator of HSCs in response to infection, but also plays a previously unrecognized role in HSC development in the absence of infection and inflammation. The baseline inflammatory signaling can be activated to promote HSC development in cell autonomous and noncell autonomous manners. However, direct response of HSCs to inflammatory stimuli is not always advantageous and excessive chronic signaling can have negative effects on HSC regulation and function.