Maternal IL-10 restricts fetal emergency myelopoiesis [scRNA-seq]
We investigated how late fetal liver (FL) mouse hematopoieitic stem and progenitor cells (HSPC) respond to inflammation, with the hypothesis that deficits in engagement of emergency myelopoiesis (EM) pathways could limit neutrophil output and contribute to perinatal neutropenia, ultimately explaining the susceptibility of neonates to inflammation and infection. We show that fetal HSPCs are biased toward erythroid and lymphoid cell production at steady state and fail to mount classical EM responses in vivo. Despite being capable of responding to EM-inducing stimuli in vitro, we find that maternal factors like interleukin-10 (IL-10) restrict fetal HSPCs from activating EM pathways in utero. Accordingly, we find that loss of maternal IL-10 restores EM activation in fetal HSPCs but at a cost of premature parturition. These results reveal the evolutionary trade-off inherent in maternal anti-inflammatory responses that maintain pregnancy but render the fetus susceptible to infection. Overall design: We sorted lineage negative, c-Kit positive cells from fetal liver of E18.5 mice and bone marrow of adult (8-12 weeks) mice. We compared wild-type fetuses to wild-type adults exposed to either PBS or LPS. We compared IL10+/- fetuses carried by wild-type mothers to IL10+/- fetuses carried by IL10-/- mothers, exposed to either PBS or LPS.