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An autocrine role for erythropoietin in mouse hematopoietic cell differentiation
1Department of Biochemistry and Molecular Biology, University of Chicago, IL 60637.
Abstract:
Erythropoietin (epo) is the primary regulator of the rate of red blood cell formation in mammals. Because it is formed in the kidney and acts on the bone marrow, its action is classically endocrine. We have shown by PCR that marrow cells contain epo mRNA and that antisense oligodeoxynucleotides, to both epo and its receptor, act on multipotent hematopoietic cells to cause a decrease in mixed erythroid:nonerythroid colonies. The antisense oligonucleotides also cause an increase in mixed nonerythroid colonies with no effect on erythroid burst formation. Sense oligonucleotides have no effect. The antisense suppression is not due to adherent cells, cycling late differentiated cells or lymphocytes, and not reversed by exogenous epo. We conclude that normal erythroid differentiation may have an early phase that is dependent on an internal autocrine mechanism involving epo and its receptor.
Insights
Normal red blood cell formation may rely on an early autocrine mechanism. Erythropoietin (EPO) and its receptor within bone marrow cells suggest an internal signaling pathway for erythroid differentiation.
Area of Science:
- Hematology
- Cell Biology
- Molecular Biology
Background:
- Erythropoietin (EPO) is the primary regulator of red blood cell production.
- EPO is classically considered an endocrine hormone produced by the kidney and acting on the bone marrow.
Purpose of the Study:
- To investigate the potential autocrine role of EPO in erythroid differentiation.
- To determine if bone marrow cells express EPO and its receptor, and if they are involved in regulating red blood cell formation.
Main Methods:
- Polymerase Chain Reaction (PCR) was used to detect EPO mRNA in marrow cells.
- Antisense oligodeoxynucleotides targeting EPO and its receptor were applied to multipotent hematopoietic cells.
- The effects of antisense oligonucleotides on colony formation were assessed.
Main Results:
- Antisense suppression of EPO and its receptor decreased mixed erythroid:nonerythroid colonies.
- Antisense oligonucleotides increased nonerythroid colonies without affecting erythroid burst formation.
- The observed suppression was not reversed by exogenous EPO and was independent of other cell types.
Conclusions:
- Normal erythroid differentiation may involve an early, autocrine-dependent phase.
- This phase appears to be regulated by an internal mechanism involving EPO and its receptor within hematopoietic cells.