MARIEKE ESSERS (HEIDELBERG)
INFLAMMATION OF HSCS AS A POTENTIAL DRIVER OF INEFFECTIVE HEMATOPOIESIS
1German Cancer Research Center (DKFZ), Heidelberg, Germany
2HI-STEM - Heidelberg Institute for Stem Cell Technologies and Experimental Medicine gGmbH, Germany
Mature blood and immune cells show broad inter- and intra-cell type-specific heterogeneity with
respect to their responsiveness to cytokines such as Interferons (IFNs). This diversity is of crucial
importance to maintain the capacity of the immune system to appropriately react to a wide range of
pathogenic insults, thereby mediating protective immunity.
Our data indicate that cellular heterogeneity is already established at the stem cell-level. Surprisingly,
when compared to other more mature hematopoietic cell types, HSCs display the highest expression
levels of IFN-stimulated genes (ISG), even under homeostatic conditions. Of particular note, ISG
expression analysis also confirmed significant heterogeneity within the HSC compartment itself as well
as within more differentiated defined cell populations. Thus our data suggest that part of the intra-cell
heterogeneity is already established at the stem cell-level and this IFN priming can be stably inherited
to mature blood and immune cells. Critically, under inflammatory stress, populations with high IFN-priming
mounted acute type-I IFN responses much more efficiently if compared to populations with
low IFN-priming, suggesting that not only homeostatic IFN-priming but also responsiveness to acute
IFNs is clonally determined at the stem cell level. This finding will likely have far-reaching implications
for the understanding of biological processes involved in antiviral responses, cancer
immunosurveillance as well as autoimmunity.
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# shared corresponding author
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