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Abstract: TH-PO657

Inflammation-Induced Alterations in Erythropoiesis at the Single Cell Level

Session Information

  • Anemia and Iron Metabolism
    November 03, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
    Abstract Time: 10:00 AM - 12:00 PM

Category: Anemia and Iron Metabolism

  • 200 Anemia and Iron Metabolism

Authors

  • Thomas, Jane Joy, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States
  • Courbon, Guillaume, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States
  • Martin, Aline, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States
  • David, Valentin, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States
Background

Inflammation is a common determinant of anemia in patients with chronic kidney disease (CKD). Inflammation restricts bone marrow (BM) erythropoiesis, due to hepcidin-mediated hypoferremia, and increases erythrophagocytosis. In addition, pro-inflammatory cytokines act on erythroid cells to suppress erythroid differentiation. Splenic hematopoiesis helps maintain erythroid homeostasis in inflammation, but the exact mechanisms are poorly understood.

Methods

To investigate the immediate effects of inflammation on BM and on the spleen (SP), we injected 6 week-old mice with a single dose of saline (Ctr) or 250 ng/g IL-1β (IF) and performed single cell RNA sequencing on BM and SP cells from Ctr and IF mice collected 4 hours post-injection. We examined the hematopoietic progenitors and terminally differentiated cells response to IF using differentiation-specific molecular markers.

Results

Compared to Ctr, IF rapidly led to an increased recruitment of precursors to myeloid progenitors in BM. In addition, IF increased the number of lymphoid and megakaryocytic progenitors at the expense of the erythroid lineage in BM. In contrast, IF increased the number of terminally differentiated cells detected in SP. Indeed, while the number of lymphoid progenitors and precursors increased in BM, the number of terminally differentiated B, T and NK cells increased in SP in response to IF. A similar effect was seen in the megakaryocytic lineage resulting in an increased number of megakaryocytes in SP during IF. Interestingly, we further found that SP-differentiated erythroid cells were identical to BM erythroblasts, suggesting that trafficking of BM erythroid progenitors to the SP, rather than de novo recruitment of splenic precursors, maintains extramedullary erythropoiesis. However, in addition to mature reticulocytes, we found an alternate cluster of cells differentiating from orthochromatic erythroblasts in SP that was quasi-absent in BM. This cluster increased in response to IF, and shows a reduction in apoptotic markers and an increase in mature reticulocyte markers compared to steady state reticulocytes.

Conclusion

In aggregate, our results suggest that IF leads to increased trafficking of erythroid progenitors from the BM to the SP. Further maturing of erythroid progenitors in the SP results in reticulocytes that might be functionally distinct from BM cells.

Funding

  • NIDDK Support