WASH is required for the differentiation commitment of hematopoietic stem cells in a c-Myc–dependent manner，Journal of Experimental Medicine，Sep.15, 2014
发布时间：2014年09月16日
Journal of Experimental Medicine，Published September 15, 2014 , doi: 10.1084/jem.20140169
WASH is required for the differentiation commitment of hematopoietic stem cells in a c-Myc–dependent manner
Pengyan Xia,1,2 Shuo Wang,1 Guanling Huang,1,2 Pingping Zhu,1 Man Li,1,2 Buqing Ye,1 Ying Du,1 and Zusen Fan1
Abstract
Hematopoiesis is fully dependent on hematopoietic stem cells (HSCs) that possess the capacity to self-renew and differentiate into all blood cell lineages. WASH, Wiskott–Aldrich syndrome protein (WASP) and SCAR homologue (WASH) is involved in endosomal sorting as an actin-nucleating protein. Here, we show that conditional WASH deletion in the hematopoietic system causes defective blood production of the host, leading to severe cytopenia and rapid anemia. WASH deficiency causes the accumulation of long-term (LT)-HSCs in bone marrow and perturbs their differentiation potential to mature blood lineages. Importantly, WASH is located in the nucleus of LT-HSCs and associates with the nucleosome remodeling factor (NURF) complex. WASH assists the NURF complex to the promoter of c-Myc gene through its VCA domain-dependent nuclear actin nucleation. WASH deletion suppresses the transcriptional activation of c-Myc gene and impairs the differentiation of LT-HSCs. WASH acts as an upstream regulator to modulate c-Myc transcription for hematopoietic regulation.
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WASH is required for the differentiation commitment of hematopoietic stem cells in a c-Myc–dependent manner，Journal of Experimental Medicine，Sep.15, 2014
Journal of Experimental Medicine，Published September 15, 2014 , doi: 10.1084/jem.20140169
WASH is required for the differentiation commitment of hematopoietic stem cells in a c-Myc–dependent manner
Pengyan Xia,1,2 Shuo Wang,1 Guanling Huang,1,2 Pingping Zhu,1 Man Li,1,2 Buqing Ye,1 Ying Du,1 and Zusen Fan1
Abstract
Hematopoiesis is fully dependent on hematopoietic stem cells (HSCs) that possess the capacity to self-renew and differentiate into all blood cell lineages. WASH, Wiskott–Aldrich syndrome protein (WASP) and SCAR homologue (WASH) is involved in endosomal sorting as an actin-nucleating protein. Here, we show that conditional WASH deletion in the hematopoietic system causes defective blood production of the host, leading to severe cytopenia and rapid anemia. WASH deficiency causes the accumulation of long-term (LT)-HSCs in bone marrow and perturbs their differentiation potential to mature blood lineages. Importantly, WASH is located in the nucleus of LT-HSCs and associates with the nucleosome remodeling factor (NURF) complex. WASH assists the NURF complex to the promoter of c-Myc gene through its VCA domain-dependent nuclear actin nucleation. WASH deletion suppresses the transcriptional activation of c-Myc gene and impairs the differentiation of LT-HSCs. WASH acts as an upstream regulator to modulate c-Myc transcription for hematopoietic regulation.
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文章链接：http://jem.rupress.org/content/early/2014/09/10/jem.20140169.full