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Blood, 15 September 2002, Vol. 100, No. 6, pp. 2063-2070
HEMATOPOIESIS
The cytoplasmic domain of Mpl receptor transduces exclusive
signals in embryonic and fetal hematopoietic cells
Cécile Challier,
Laurence Cocault,
Rolande Berthier,
Nadine Binart,
Isabelle Dusanter-Fourt,
Georges Uzan, and
Michèle Souyri
From the Institut National de la Santé et de la
Recherche Médicale (INSERM) U506, Hôpital Paul Brousse,
Villejuif, France; INSERM U238, Centre d'Etudes Atomique,
Grenoble, France; INSERM U363, Hôpital Cochin and INSERM U344,
Hôpital Necker, Paris, France.
The Mpl receptor plays an important role at the level of adult
hematopoietic stem cells, but little is known of its function in
embryonic and fetal hematopoiesis. We investigated the signals sent by
the MPL cytoplasmic domain in fetal liver hematopoietic progenitors and
during embryonic stem (ES) cell hematopoietic commitment. Mpl was found
to be expressed only from day 6 of ES cell differentiation into
embryoid bodies. Therefore, we expressed Mpl in undifferentiated ES
cells or in fetal progenitors and studied the effects on
hematopoietic differentiation. To avoid the inadvertent effect
of thrombopoietin, we used a chimeric receptor, PM-R,
composed of the extracellular domain of the prolactin receptor (PRL-R) and the transmembrane and cytoplasmic domains of Mpl. This allowed activation of the receptor with a hormone that is not involved in
hematopoietic differentiation and assessment of the specificity of responses to Mpl by comparing PM-R with another PRL-R chimeric receptor that includes the cytoplasmic domain of the erythropoietin receptor (EPO-R) ([PE-R]). We have shown that the cytoplasmic domain of the Mpl receptor transduces exclusive signals in fetal liver
hematopoietic progenitors as compared with that of EPO-R and that it
promotes hematopoietic commitment of ES cells. Our findings demonstrate
for the first time the specific role of Mpl in early embryonic
or fetal hematopoietic progenitors and stem cells.
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