NfκB signaling dynamics and their target genes differ between mouse blood cell types and induce distinct cell behavior.

ABSTRACT

Cells can use signaling pathway activity over time (ie, dynamics) to control cell fates. However, little is known about the potential existence and function of signaling dynamics in primary hematopoietic stem and progenitor cells (HSPCs). Here, we use time-lapse imaging and tracking of single murine HSPCs from green fluorescent protein-p65/H2BmCherry reporter mice to quantify their nuclear factor κB (NfκB) activity dynamics in response to tumor necrosis factor α and interleukin 1ß. We find response dynamics to be heterogeneous between individual cells, with cell type-specific dynamics distributions. Transcriptome sequencing of single cells physically isolated after live dynamics quantification shows activation of different target gene programs in cells with different dynamics. Finally, artificial induction of oscillatory NfκB activity causes changes in granulocyte/monocyte progenitor behavior. Thus, HSPC behavior can be influenced by signaling dynamics, which are tightly regulated during hematopoietic differentiation and enable cell type-specific responses to the same signaling inputs.