Inhibition of erythropoiesis by Smad6 in human cord blood hematopoietic stem cells
- Authors
- Kang, Young-Ju; Shin, Ji-woong; Yoon, Jeong-Hwan; Oh, Il-Hwan; Lee, Soon-Pyo; Kim, Suk-Young; Park, Seok Hee; Mamura, Mizuko
- Issue Date
- 13-Jul-2012
- Publisher
- ACADEMIC PRESS INC ELSEVIER SCIENCE
- Keywords
- Smad6; Human cord blood hematopoietic stem cells; Erythropoiesis; BMP
- Citation
- BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, v.423, no.4, pp.750 - 756
- Journal Title
- BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
- Volume
- 423
- Number
- 4
- Start Page
- 750
- End Page
- 756
- URI
- https://scholarworks.bwise.kr/gachon/handle/2020.sw.gachon/16281
- DOI
- 10.1016/j.bbrc.2012.06.031
- ISSN
- 0006-291X
- Abstract
- 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.
- Files in This Item
- There are no files associated with this item.
- Appears in
Collections - 의과대학 > 의학과 > 1. Journal Articles
![qrcode](https://api.qrserver.com/v1/create-qr-code/?size=55x55&data=https://scholarworks.bwise.kr/gachon/handle/2020.sw.gachon/16281)
Items in ScholarWorks are protected by copyright, with all rights reserved, unless otherwise indicated.