TY - JOUR
T1 - SOCS3 is essential in the regulation of fetal liver erythropoiesis
AU - Marine, Jean Christophe
AU - McKay, Catriona
AU - Wang, Demin
AU - Topham, David J.
AU - Parganas, Evan
AU - Nakajima, Hideaki
AU - Pendeville, Hélène
AU - Yasukawa, Hideo
AU - Sasaki, Atsuo
AU - Yoshimura, Akihiko
AU - Ihle, James N.
N1 - Funding Information:
We would like to thank Irv Weismann (Stanford) for providing the pSP65-H2K-I-LTR vector for the transgenic studies. The authors would also like to thank Suzette Wingo for her excellent technical assistance. The ES cell line used in these studies was kindly provided by Jan van Deursen. This work is supported by the Cancer Center CORE grant CA21765, by the grant RO1 DK42932 to J. N. I., by grant PO1 HL53749, and by the American Lebanese Syrian Associated Charities (ALSAC).
PY - 1999/9/3
Y1 - 1999/9/3
N2 - SOCS3 (CIS3/JAB2) is an SH2-containing protein that binds to the activation loop of Janus kinases, inhibiting kinase activity, and thereby suppressing cytokine signaling. During embryonic development, SOCS3 is highly expressed in erythroid lineage cells and is Epo independent. Transgene- mediated expression blocks fetal erythropoiesis, resulting in embryonic lethality. SOCS3 deletion results in an embryonic lethality at 12-16 days associated with marked erythrocytosis. Moreover, the in vitro proliferative capacity of progenitors is greatly increased. SOCS3-deficient fetal liver stem cells can reconstitute hematopoiesis in lethally irradiated adults, indicating that its absence does not disturb bone marrow erythropoiesis. Reconstitution of lymphoid lineages in JAK3-deficient mice also occurs normally. The results demonstrate that SOCS3 is critical in negatively regulating fetal liver hematopoiesis.
AB - SOCS3 (CIS3/JAB2) is an SH2-containing protein that binds to the activation loop of Janus kinases, inhibiting kinase activity, and thereby suppressing cytokine signaling. During embryonic development, SOCS3 is highly expressed in erythroid lineage cells and is Epo independent. Transgene- mediated expression blocks fetal erythropoiesis, resulting in embryonic lethality. SOCS3 deletion results in an embryonic lethality at 12-16 days associated with marked erythrocytosis. Moreover, the in vitro proliferative capacity of progenitors is greatly increased. SOCS3-deficient fetal liver stem cells can reconstitute hematopoiesis in lethally irradiated adults, indicating that its absence does not disturb bone marrow erythropoiesis. Reconstitution of lymphoid lineages in JAK3-deficient mice also occurs normally. The results demonstrate that SOCS3 is critical in negatively regulating fetal liver hematopoiesis.
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U2 - 10.1016/S0092-8674(00)80049-5
DO - 10.1016/S0092-8674(00)80049-5
M3 - Article
C2 - 10490101
AN - SCOPUS:0033520389
VL - 98
SP - 617
EP - 627
JO - Cell
JF - Cell
SN - 0092-8674
IS - 5
ER -