Dynamic changes in murine erythropoiesis from birth to adulthood: implications for the study of murine models of anemia

Abstract

Liver, spleen, and bone marrow are 3 key erythropoietic tissues in mammals. In the mouse, the liver is the predominant site of erythropoiesis during fetal development, the spleen responds to stress erythropoiesis, and the bone marrow is involved in maintaining homeostatic erythropoiesis in adults. However, the dynamic changes and respective contributions of the erythropoietic activity of these tissues from birth to adulthood are incompletely defined. Using C57BL/6 mice, we systematically examined the age-dependent changes in liver, spleen, and bone marrow erythropoiesis following birth. In addition to bone marrow, the liver and spleen of newborn mice sustain an active erythropoietic activity that is gradually lost during first few weeks of life. While the erythropoietic activity of the liver is lost 1 week after birth, that of the spleen is maintained for 7 weeks until the erythropoietic activity of the bone marrow is sufficient to sustain steady-state adult erythropoiesis. Measurement of the red cell parameters demonstrates that these postnatal dynamic changes are reflected by varying indices of circulating red cells. While the red cell numbers, hemoglobin concentration, and hematocrit progressively increase after birth and reach steady-state levels by week 7, reticulocyte counts decrease during this time period. Mean cell volume and mean cell hemoglobin progressively decrease and reach steady state by week 3. Our findings provide comprehensive insights into developmental changes of murine erythropoiesis postnatally and have significant implications for the appropriate interpretation of findings from the variety of murine models used in the study of normal and disordered erythropoiesis.

Differences in Steady-State Erythropoiesis in Different Mouse Bones and Postnatal Spleen

“…The role of the spleen in supporting erythropoiesis during the postnatal period has received little attention. While this paper was being revised Chen et al (2021) published a paper on spleen erythropoiesis in developing mice which supports our results. We have shown that in the spleen a significant decrease in erythroid precursors are seen at about 4 weeks of age.…”

Loss of Parathyroid Hormone Receptor Signaling in Osteoprogenitors Is Associated With Accumulation of Multiple Hematopoietic Lineages in the Bone Marrow

“…(71) In mice the spleen can support stress erythropoiesis in response to acute anemia, (72) and is an active site of erythropoiesis in the first weeks after birth until steady-state erythropoiesis is established in the BM. (73) The findings in the spleen are in striking contrast to the thymus, where T cell precursor differentiation appears to proceed normally in PTH1R-OsxKO mice. Early T cell precursors, derived from common lymphoid progenitors, differentiate in the thymus into mature CD4 and CD8 T cells.…”

Membrane Properties of Human Induced Pluripotent Stem Cell-Derived Cultured Red Blood Cells

“…As discussed in more detail below, cell size and Hb content might not only be influenced by the maturation stage of erythroid cells, but also by the developmental wave of human erythropoiesis [ 12 ]. Besides different growth kinetics and altered expression of transcription factors during erythropoiesis [ 32 , 33 ], fetal liver-derived RBCs like CB cells are described to have a higher volume and Hb content in comparison to BM-derived adult RBCs [ 10 , 11 ]. Interestingly, the Hb concentration in adult nRBCs was lower than in cRBC_iPSC and CB-derived nRETs, but comparable to cRBCs derived from adult HSPCs (cRBC_adult) [ 10 ].…”

“…Whereas CB cells originate from fetal liver erythropoiesis, PB cells originate from adult bone marrow (BM) erythropoiesis. There is increasing evidence that RBCs from different developmental waves differ in their cellular features like hemoglobin (Hb) composition, Hb content, and cell size [ 10 , 11 , 12 ].…”