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Nature 461, 537-541 (24 September 2009) | doi:10.1038/nature08313: d1 P# h$ i0 v' i4 g: I( z: v
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Reactive oxygen species prime Drosophila haematopoietic progenitors for differentiation
$ P* \1 U# E) Q, }2 d, ^( Y+ ?$ `$ R8 m) X
Edward Owusu-Ansah1,5 & Utpal Banerjee1,2,3,4
4 |7 y |- J( {( ^
( x. C2 t/ {; q F. K; n1 Department of Molecular, Cell and Developmental Biology,( N; J: l6 a8 g/ j2 v
2 Molecular Biology Institute,
7 b' s4 S6 w' l3 i- a% C3 Department of Biological Chemistry,
, [) I) s2 o* w2 k4 Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, California 90095, USA
0 H0 g4 c) K- s; p6 K5 Present address: Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA.; ?" o/ L E0 O P
6 Correspondence to: Utpal Banerjee1,2,3,4 Correspondence and requests for materials should be addressed to U.B.
% V7 _; r) ?& S. I' V7 J
4 P, ~5 R7 z: h5 h3 yReactive oxygen species (ROS), produced during various electron transfer reactions in vivo, are generally considered to be deleterious to cells1. In the mammalian haematopoietic system, haematopoietic stem cells contain low levels of ROS. However, unexpectedly, the common myeloid progenitors (CMPs) produce significantly increased levels of ROS2. The functional significance of this difference in ROS level in the two progenitor types remains unresolved2, 3. Here we show that Drosophila multipotent haematopoietic progenitors, which are largely akin to the mammalian myeloid progenitors4, display increased levels of ROS under in vivo physiological conditions, which are downregulated on differentiation. Scavenging the ROS from these haematopoietic progenitors by using in vivo genetic tools retards their differentiation into mature blood cells. Conversely, increasing the haematopoietic progenitor ROS beyond their basal level triggers precocious differentiation into all three mature blood cell types found in Drosophila, through a signalling pathway that involves JNK and FoxO activation as well as Polycomb downregulation. We conclude that the developmentally regulated, moderately high ROS level in the progenitor population sensitizes them to differentiation, and establishes a signalling role for ROS in the regulation of haematopoietic cell fate. Our results lead to a model that could be extended to reveal a probable signalling role for ROS in the differentiation of CMPs in mammalian haematopoietic development and oxidative stress response. |
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发表于 2009-9-24 10:09
发表于 2009-9-24 14:46
