MicroRNAs play a role in the development of human hematopoietic stem cells

Journal of Cellular Biochemistry - Tập 104 Số 3 - Trang 805-817 - 2008
Rongxia Liao1, Jianguo Sun2, Liang Zhang3,4, Guiyu Lou1, Min Chen1, Zhou Du-jin1,5,6, Zhengtang Chen2,5,6, Shaoxiang Zhang7
1Department of Biochemistry and Molecular Biology, Third Military Medical University, Chongqing 400038, China
2Cancer Institute of PLA, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China
3Capitalbio Corporation
4National Engineering Research Center for Beijing Biochip Technology, Beijing 102206, China
5Dujin Zhou, Department of Biochemistry and Molecular Biology, Third Military Medical University, Chongqing 400038, China.
6Zhengtang Chen, Cancer Institute of PLA, Xinqiao Hospital, Third Military Medical University, Chongqing, 400037.
7Department of Anatomy, College of Medicine, Third Military Medical University, Chongqing 400038, China

Tóm tắt

AbstractMicroRNAs (miRNAs) are a class of recently discovered noncoding RNA genes that post‐transcriptionally regulate gene expression. It is becoming clear that miRNAs play an important role in the regulation of gene translation during development. However, in mammals, expression data are principally based on whole tissue analysis and are still very incomplete. We isolated CD34+CD38− hematopoietic stem cells (HSCs) from human umbilical cord blood, on the basis of cell‐surface markers using fluorescence‐activated cell sorting (FACS). Also, CD34+ subpopulation was FACS isolated as the control. Next, using microarray containing oligonucleotides corresponding to 517 miRNAs from human, mouse, and rat genomes, we obtained miRNA gene expression profiles of both subpopulations. We focused on the HSCs correlative miRNAs with comparison to the control. The miRNAs of particular interest were confirmed by real‐time RT‐PCR. HSCs‐overexpressed hsa‐miR‐520h and underexpressed hsa‐miR‐129 were selected for target prediction and analysis. The result showed that EIF2C3 and CAMTA1, genes related to miRNAs processing or transcription regulation, were proved to be real targets for hsa‐miR‐129. And ABCG2, involved in stemness maintaining, a real target for hsa‐miR‐520h. Finally, we chose hsa‐miR‐520h, enriched in HSCs but low in CD34+ cells, for functional characterization, because of its possible role in differentiation of HSCs by regulating ABCG2. As a result, hsa‐miR‐520h transduction into CD34+ cells greatly increased number of different progenitor colonies in Colony‐Forming‐Cell assays, suggesting that hsa‐miR‐520h may promote differentiation of HSCs into progenitor cells by inhibiting ABCG2 expression. This study paves the way for identifying HSC‐specific miRNAs and their roles in HSC development. J. Cell. Biochem. 104: 805–817, 2008. © 2008 Wiley‐Liss, Inc.

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Tài liệu tham khảo

10.1016/S0092-8674(03)00428-8

10.1016/j.febslet.2005.09.040

10.1074/jbc.M510275200

10.1073/pnas.242606799

10.1073/pnas.0404432101

10.1126/science.1091903

10.1093/nar/gni178

10.1634/stemcells.2004-0093

10.1073/pnas.0610983104

10.1073/pnas.0703037104

10.1097/01.moh.0000231422.00407.be

10.1016/j.tibs.2004.07.001

10.1016/S1534-5807(03)00227-2

10.2174/1573406410602060555

10.1002/jnr.20994

10.1074/jbc.M313599200

10.1002/gcc.10316

Nakatani K, 2004, Cell cycle‐dependent transcriptional regulation of calmodulin‐binding transcription activator 1 in neuroblastoma cells, Int J Oncol, 24, 1407

10.1158/0008-5472.CAN-05-0626

10.1016/j.leukres.2005.09.001

10.1016/S0888-7543(03)00129-0

10.1038/nmeth704

10.1038/nature03441

Thông tin
Thông tin xuất bản

Journal of Cellular Biochemistry

Tập 104 Số 3

805-817

Thông tin tác giả