Absence of cytokine receptor-dependent specificity in red blood cell differentiation in vivo

Absence of cytokine receptor-dependent specificity in red blood cell differentiation in vivo

^*Gladstone Institute of Virology and Immunology, and ^†Department of Medicine, School of Medicine, University of California, San Francisco, San Francisco, CA 94141; ^‡Departments of Medicine and Cell Biology, Washington University School of Medicine, St. Louis, MO 63110, and ^§Ralph H. Johnson Department of Veterans Affairs Medical Center and Department of Medicine, Medical University of South Carolina, Charleston, SC 29401

Communicated by Philip W. Majerus, Washington University School of Medicine, St. Louis, MO (received for review February 12, 1998)

Abstract

Erythropoietin (EPO) is required for red blood cell development, but whether EPO-specific signals directly instruct erythroid differentiation is unknown. We used a dominant system in which constitutively active variants of the EPO receptor were introduced into erythroid progenitors in mice. Chimeric receptors were constructed by replacing the cytoplasmic tail of constitutively active variants of the EPO receptor with tails of diverse cytokine receptors. Receptors linked to granulocyte or platelet production supported complete erythroid development in vitro and in vivo, as did the growth hormone receptor, a nonhematopoietic receptor. Therefore, EPOR-specific signals are not required for terminal differentiation of erythrocytes. Furthermore, we found that cellular context can influence cytokine receptor signaling.

Footnotes

↵ ¶ To whom reprint requests should be addressed.
A commentary on this article begins on page 6573.
ABBREVIATIONS:

EPO,

erythropoietin;

EPOR,

EPO receptor;

cEPOR,

constitutively active variants of the EPOR;

BFU-D,

blast-forming unit-erythroid;

CFU-E,

colony-forming unit-erythroid;

G-CSFR,

granulocyte colony-stimulating factor receptor;

STAT,

signal transducer and activator of transcription;

SFFV,

spleen focus-forming virus;

GHR,

growth hormone receptor