Retrotransposons are transposable DNA elements that in hematopoietic stem cells (HSC) can be activated by aging, irradiation or chemotherapy. In Science, Phan et al. report the upregulation of retrotransposons, including endogenous retroviruses and long interspersed nuclear elements and the induction of IFN-regulated genes in spleen, but not bone marrow HSCs, as well as phosphorylation of STING and expression of Ifna in spleen and bone marrow HSCs in pregnant, but not non-pregnant, mice. Retrotransposons and IFN-regulated genes were also induced in spleen HSCs by serial bleeding and estradiol treatment. Genomic regions that encode the upregulated retroposons were more accessible in spleen HSCs from pregnant or estrogen-treated mice compared with bone marrow HSCs (spleen HSCs were too rare) from non-pregnant or non-treated mice reverse transcriptase inhibitors and STING or cGAS deficiency reduced the frequency of spleen HSCs and spleen and bone marrow erythroid progenitors, and red blood cell counts in pregnant, but not non-pregnant, mice. STING was required for the expression of Ifna and IFN-regulated genes in spleen HSCs during pregnancy. Compared with non-pregnant women, blood HSCs from pregnant women exhibited increased retrotransposon transcription and changes in the expression of IFN-regulated genes, and pregnant, but not non-pregnant, women who took reverse transcriptase inhibitors became anemic, which suggests a conservation of these mechanisms.

Original reference: Science https://doi.org/10.1126/science.ado6836 (2024)