Functional Network Reconstruction Reveals Somatic Stemness Genetic Maps and Dedifferentiation‐Like Transcriptome Reprogramming Induced by GATA2

Somatic stem cell transplantation holds great promise in regenerative medicine. The best‐characterized adult stem cells are mesenchymal stem cells (MSCs), neural stem cells (NSCs), and CD133+ hematopoietic stem cells (HSCs). The applications of HSCs are hampered since these cells are difficult to ma...

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Published in:Stem cells (Dayton, Ohio) Ohio), 2008-05, Vol.26 (5), p.1186-1201
Main Authors: Huang, Tse‐Shun, Hsieh, Jui‐Yu, Wu, Yu‐Hsuan, Jen, Chih‐Hung, Tsuang, Yang‐Hwei, Chiou, Shih‐Hwa, Partanen, Jukka, Anderson, Heidi, Jaatinen, Taina, Yu, Yau‐Hua, Wang, Hsei‐Wei
Format: Article
Language:English
Subjects:
AC133 Antigen
Antigens, CD - metabolism
Antigens, CD34 - metabolism
CD133+ stem cell
Cell Dedifferentiation
Cell Line
Cell Separation
Cellular Reprogramming
Chromosome Mapping
Cluster Analysis
Dedifferentiation
Embryonic Stem Cells - cytology
Embryonic Stem Cells - metabolism
Endothelial Cells - cytology
Endothelial Cells - metabolism
GATA2
GATA2 Transcription Factor - genetics
GATA2 Transcription Factor - metabolism
Gene Expression Profiling
Gene Expression Regulation
Gene Regulatory Networks
Glycoproteins - metabolism
Hematopoietic Stem Cells - cytology
Hematopoietic Stem Cells - metabolism
Humans
Mesenchymal Stromal Cells - cytology
Mesenchymal Stromal Cells - metabolism
Neurons - cytology
Neurons - metabolism
Oligonucleotide Array Sequence Analysis
Peptides - metabolism
Somatic stem cell
Stem Cells - cytology
Stem Cells - metabolism
Systems biology
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Summary:Somatic stem cell transplantation holds great promise in regenerative medicine. The best‐characterized adult stem cells are mesenchymal stem cells (MSCs), neural stem cells (NSCs), and CD133+ hematopoietic stem cells (HSCs). The applications of HSCs are hampered since these cells are difficult to maintain in an undifferentiated state in vitro. Understanding genes responsible for stem cell properties and their interactions will help on this issue. The construction of stem cell genetic networks will also help to develop rational strategies to revert somatic cells back to a stem‐like state. We performed a systemic study on human CD133+ HSCs, NSCs, MSCs, and embryonic stem cells and two different progenies of CD133+ HSCs, microvascular endothelial cells (MVECs) and peripheral blood mononuclear cells. Genes abundant in each or in all three somatic stem cells were identified. We also observed complex genetic networks functioning in postnatal stem cells, in which several genes, such as PTPN11 and DHFR, acted as hubs to maintain the stability and connectivity of the whole genetic network. Eighty‐seven HSC genes, including ANGPT1 and GATA2, were independently identified by comparing CD34+CD33−CD38− hematopoietic stem cells with CD34+ precursors and various matured progenies. Introducing GATA2 into MVECs resulted in dedifferentiation‐like transcriptome reprogramming, with HSC genes (such as ANGPT1) being up and endothelial genes (such as EPHB2) being down. This study provides a foundation for a more detailed understanding of human somatic stem cells. Expressing the newly discovered stem cell genes in matured cells might lead to a global reversion of somatic transcriptome to a stem‐like status. Disclosure of potential conflicts of interest is found at the end of this article.
ISSN:1066-5099
1549-4918
DOI:10.1634/stemcells.2007-0821