期刊
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
卷 423, 期 4, 页码 750-756出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2012.06.031
关键词
Smad6; Human cord blood hematopoietic stem cells; Erythropoiesis; BMP
资金
- Mochida Memorial Foundation for Medical and Pharmaceutical Research, Japan
- Association for Preventive Medicine of Japan
- Kwang-dong Pharmaceutical Co., Republic of Korea
- Korea Foundation for Cancer Research [KFCR-2009-004]
- National Research Foundation of Korea [2011-0019638]
- Bio Technology R&D Program, Republic of Korea [20090081756]
- National Research Foundation of Korea [2009-0081756, 2011-0019638] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
Bone morphogenetic proteins (BMPs) that belong to the transforming growth factor-beta (TGF-beta) superfamily cytokines, play crucial roles in hematopoiesis. However, roles of Smad6 in hematopoiesis remained unknown in contrast to the other inhibitory Smad (I-Smad), Smad7. Here we show that Smad6 inhibits erythropoiesis in human CD34(+) cord blood hematopoietic stem cells (HSCs). Smad6 was specifically expressed in CD34(+) cord blood HSCs, which was correlated with the expression of BMP2/4/6/7 and BMP type I receptor (BMPRI). BMP-specific receptor-regulated Smads (R-Smads), Smad1 and Smad5 in cooperation with Smad4 induced transcription of the Smad6 gene. Instead of affecting cell cycle, apoptosis, self-renewal, and stemness of CD34(+) cells. Smad6 knockdown enhanced, whereas Smad6 overexpression suppressed erythropoiesis in stem cell culture and colony formation assay. Consistently, Smad6 suppressed the expression of the genes essential for erythropoiesis, such as Kruppel-like factor 1 (erythroid) (KLF1/EKLF) and GATA binding protein 2 (GATA-2). Promoter analyses showed that Smad6 repressed Smad5/4-induced transcription of the Klf1 gene. Thus, our data suggest that Smad6 indirectly maintains stemness by preventing spontaneous erythropoiesis in HSCs. (C) 2012 Elsevier Inc. All rights reserved.
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