Adult bone marrow erythropoiesis is primarily homeostatic, constantly producing new erythrocytes throughout adult life. However, during fetal development and in response to acute anemia in adults the situation is dramatically different. At these times stress erythropoiesis predominates, which rapidly produces large numbers of new erythrocytes. Little is known about the mechanisms that regulate stress erythropoiesis in humans. My laboratory utilizes a murine model for stress erythropoiesis and has demonstrated that BMP4 dependent signals are required for the rapid expansion of a specialized population of stress erythroid progenitors during the recovery from acute anemia. These progenitors have greater potential to rapidly generate large numbers of new erythrocytes than bone marrow steady state progenitors. In this proposal we will further characterize the BMP4 dependent stress erythropoiesis pathway by taking advantage of a robust experimental system that utilizes erythroid recovery during the period immediately following bone marrow transplant. Our preliminary data show that this recovery is mediated by erythroid short-term radioprotective cells, which utilize the BMP4 dependent stress erythropoiesis pathway. In the first aim, we will examine the mechanisms that regulate BMP4 expression in the spleen during the recovery from bone marrow transplant. In the second aim, we will examine the role of Hedgehog and BMP4 signaling in the specification and expansion of stress erythroid progenitors in the spleen. While in the third aim, we will examine the regulation of Scl, Gata2 and Gata1 by Hedgehog, BMP4 and hypoxia. These studies will provide key basic information concerning the regulation of stress erythropoiesis, which can be built upon to develop new therapies to treat anemia.

Public Health Relevance

This project outlines experiments designed to investigate the mechanisms that regulate the rapid production of new red blood cells at times of acute need. The information gathered from this work will provide key basic information for the development of new therapies for anemia and other blood diseases.

National Institute of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Research Project (R01)
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Hematopoiesis Study Section (HP)
Program Officer
Bishop, Terry Rogers
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Pennsylvania State University
Veterinary Sciences
Schools of Earth Sciences/Natur
University Park
United States
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Liao, Chang; Carlson, Bradley A; Paulson, Robert F et al. (2018) The intricate role of selenium and selenoproteins in erythropoiesis. Free Radic Biol Med 127:165-171
Liao, Chang; Prabhu, K Sandeep; Paulson, Robert F (2018) Monocyte-derived macrophages expand the murine stress erythropoietic niche during the recovery from anemia. Blood 132:2580-2593
Liao, Chang; Hardison, Ross C; Kennett, Mary J et al. (2018) Selenoproteins regulate stress erythroid progenitors and spleen microenvironment during stress erythropoiesis. Blood 131:2568-2580
Xiang, Jie; Wu, Dai-Chen; Chen, Yuanting et al. (2015) In vitro culture of stress erythroid progenitors identifies distinct progenitor populations and analogous human progenitors. Blood 125:1803-12
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Paulson, Robert F; Shi, Lei; Wu, Dai-Chen (2011) Stress erythropoiesis: new signals and new stress progenitor cells. Curr Opin Hematol 18:139-45
Kaushal, Naveen; Hegde, Shailaja; Lumadue, Jeanne et al. (2011) The regulation of erythropoiesis by selenium in mice. Antioxid Redox Signal 14:1403-12

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