Table 2.

Major unanswered questions.

Do HSCs differentially respond to signals transmitted through MyD88 versus TRIF, or even through the individual TLRs?

Memory T cells and memory B cells share with HSCs the properties of quiescence, periodic reactivation, and a return to quiescence. Do TLRs signals or inflammatory signals similarly influence integrity of these long-lived memory compartments, including proliferation and exhaustion?

What are the implications of concerted stimulation of TLRs on the HSCs and their downstream progeny?

Do therapeutic TLR agonists affect long-term HSC potential including self-renewal and multi-lineage differentiation?