HEMATOPOIESIS AND STEM CELLS| AUGUST 27, 2020
Megakaryocyte TGFβ1 partitions erythropoiesis into immature progenitor/stem cells and maturing precursorsSilvana Di Giandomenico, Pouneh Kermani, Nicole Mollé, Maria Mia Yabut, Ghaith Abu-Zeinah, Thomas Stephens, Nassima Messali, Ryan Schreiner, Fabienne Brenet, Shahin Rafii, Joseph M. Scandura
Blood (2020) 136 (9): 1044–1054.
https://doi.org/10.1182/blood.2019003276
Key PointsAbstractErythropoietin (EPO) provides the major survival signal to maturing erythroid precursors (EPs) and is essential for terminal erythropoiesis. Nonetheless, progenitor cells can irreversibly commit to an erythroid fate well before EPO acts, risking inefficiency if these progenitors are unneeded to maintain red blood cell (RBC) counts. We identified a new modular organization of erythropoiesis and, for the first time, demonstrate that the pre-EPO module is coupled to late EPO-dependent erythropoiesis by megakaryocyte (Mk) signals. Disrupting megakaryocytic transforming growth factor β1 (Tgfb1) disorganized hematopoiesis by expanding the pre-EPO pool of progenitor cells and consequently triggering significant apoptosis of EPO-dependent EPs. Similarly, pharmacologic blockade of TGFβ signaling in normal mice boosted the pre-EPO module, leading to apoptosis of EPO-sensitive EPs. Subsequent treatment with low-dose EPO triggered robust RBC production in both models. This work reveals modular regulation of erythropoiesis and offers a new strategy for overcoming chronic anemias.
Subjects:
Hematopoiesis and Stem Cells, Red Cells, Iron, and Erythropoiesis
Topics:
apoptosis, electrophysiological studies, erythroid progenitor cells, erythropoiesis, erythropoietin, flow cytometry, megakaryocytes, mice, stem cells, transforming growth factors
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