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bioRxiv · 10.1101/2022.07.18.500483

Basal type I interferon signaling has only modest effects on neonatal and juvenile hematopoiesis

Li, Y.·Yang, W.·Wang, H. C.·Patel, R. M.·Casey, E. B.·Denby, E.·Magee, J. A.
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Abstract

Type I interferon (IFN-1) regulates gene expression and hematopoiesis both during development and in response to inflammatory stress. We previously showed that during development, hematopoietic stem cells (HSCs) and multipotent progenitors (MPPs) induce IFN-1 target genes shortly before birth in mice. This coincides with the onset of a transition to adult hematopoiesis, and it drives expression of genes associated with antigen presentation. However, it is not clear whether perinatal IFN-1 modulates hematopoietic output, as has been observed in contexts of inflammation. We have characterized hematopoiesis at several different stages of blood formation, from HSCs to mature blood cells, and found that loss of the IFN-1 receptor (IFNAR1) leads to depletion of several phenotypic HSC and MPP subpopulations in neonatal and juvenile mice. Committed lymphoid and myeloid progenitor populations simultaneously expand. These changes had surprisingly little effect on production of more differentiated blood cells. Cellular Indexing of Transcriptomes and Epitopes by sequencing (CITE-seq) resolved the discrepancy between the extensive changes in progenitor numbers and modest changes in hematopoiesis, revealing stability in most MPP populations in Ifnar1-deficient neonates when the populations were identified based on gene expression rather than surface marker phenotype. Thus, basal IFN-1 signaling has only modest effects on hematopoiesis. Discordance between transcriptionally- and phenotypically-defined MPP populations may impact interpretations of how IFN-1 shapes hematopoiesis in other contexts, such as aging or inflammation. KEY POINTSO_LILoss of type I Interferon signaling in neonatal mice depletes immature blood progenitors without compromising postnatal hematopoiesis C_LIO_LIProgenitor populations remain intact when measured by single cell transcriptomes rather than surface marker phenotypes C_LI

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Li, Y., Yang, W., Wang, H. C., Patel, R. M., Casey, E. B., Denby, E., Magee, J. A.. 2022-07-18. Basal type I interferon signaling has only modest effects on neonatal and juvenile hematopoiesis. https://doi.org/10.1101/2022.07.18.500483

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