Abstract
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.
| Original language | English |
|---|---|
| Pages (from-to) | 1186-1201 |
| Number of pages | 16 |
| Journal | Stem Cells |
| Volume | 26 |
| Issue number | 5 |
| DOIs | |
| Publication status | Published - May 2008 |
| Externally published | Yes |
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Keywords
- CD133 stem cell
- Dedifferentiation
- GATA2
- Somatic stem cell
- Systems biology
ASJC Scopus subject areas
- Cell Biology
- Developmental Biology
- Molecular Medicine
- Medicine(all)
Cite this
Functional network reconstruction reveals somatic stemness genetic maps and dedifferentiation-like transcriptome reprogramming induced by GATA2. / 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.
In: Stem Cells, Vol. 26, No. 5, 05.2008, p. 1186-1201.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Functional network reconstruction reveals somatic stemness genetic maps and dedifferentiation-like transcriptome reprogramming induced by GATA2
AU - Huang, Tse Shun
AU - Hsieh, Jui Yu
AU - Wu, Yu Hsuan
AU - Jen, Chih Hung
AU - Tsuang, Yang Hwei
AU - Chiou, Shih Hwa
AU - Partanen, Jukka
AU - Anderson, Heidi
AU - Jaatinen, Taina
AU - Yu, Yau Hua
AU - Wang, Hsei Wei
PY - 2008/5
Y1 - 2008/5
N2 - 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.
AB - 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.
KW - CD133 stem cell
KW - Dedifferentiation
KW - GATA2
KW - Somatic stem cell
KW - Systems biology
UR - http://www.scopus.com/inward/record.url?scp=47949111048&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=47949111048&partnerID=8YFLogxK
U2 - 10.1634/stemcells.2007-0821
DO - 10.1634/stemcells.2007-0821
M3 - Article
C2 - 18308945
AN - SCOPUS:47949111048
VL - 26
SP - 1186
EP - 1201
JO - Stem Cells
JF - Stem Cells
SN - 1066-5099
IS - 5
ER -