Work

Author Response: Differential regulation by CD47 and thrombospondin-1 of extramedullary erythropoiesis in mouse spleen

Year: 2023

Type: peer-review

Abstract: Extramedullary erythropoiesis is not expected in healthy adult mice, but erythropoietic gene expression was elevated in lineage-depleted spleen cells from cd47 -/-mice.Expression of several genes associated with early stages of erythropoiesis was elevated in mice lacking CD47 or its signaling ligand thrombospondin-1, consistent with previous evidence that this signaling pathway inhibits expression of multipotent stem cell transcription factors in spleen.In contrast, cells expressing markers of committed erythroid progenitors were more abundant in cd47 -/-spleens but significantly depleted in thbs1 -/-spleens.Single cell transcriptome and flow cytometry analyses indicated that loss of CD47 is associated with accumulation and increased proliferation in spleen of Ter119 -CD34 + progenitors and Ter119 + CD34 -committed erythroid progenitors with elevated mRNA expression of Kit, Ermap, and Tfrc, Induction of committed erythroid precursors is consistent with the known function of CD47 to limit the phagocytic removal of aged erythrocytes.Conversely, loss of thrombospondin-1 delays the turnover of aged red blood cells, which may account for the suppression of committed erythroid precursors in thbs1 -/-spleens relative to basal levels in wild type mice.In addition to defining a role for CD47 to limit extramedullary erythropoiesis, these studies reveal a thrombospondin-1-dependent basal level of extramedullary erythropoiesis in adult mouse spleen. eLife assessmentThis study presents a valuable finding on the cell composition in mouse spleen depleted for the CD47 receptor and its signaling ligand Thrombospondin in hematopoietic differentiation.The supporting evidence is convincing with analytical improvements on the individual contributions of the signaling components and with functional studies.This work has implications for the role of CD47/Thsp in extramedullary erythropoiesis in mouse spleen and will be of interest to researchers in cell signaling, transfusion medicine, and cell therapy.

Source: eLife

DOI: 10.7554/elife.92679.1.sa3

Authors: Rajdeep Banerjee, Thomas J. Meyer, Margaret C. Cam, Sukhbir Kaur, David D. Roberts

Institutions: National Institutes of Health, National Cancer Institute, Center for Cancer Research, National Cancer Institute

Language: English

Topic: Phagocytosis and Immune Regulation

Subfield: Immunology

Field: Immunology and Microbiology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $2,500