Functional network reconstruction reveals somatic stemness genetic maps and dedifferentiation-like transcriptome reprogramming induced by GATA2

Tse Shun Huang, Jui Yu Hsieh, Yu Hsuan Wu, Chih Hung Jen, Yang Hwei Tsuang, Shih Hwa Chiou, Jukka Partanen, Heidi Anderson, Taina Jaatinen, Yau Hua Yu, Hsei Wei Wang

Research output: Contribution to journalArticle

37 Citations (Scopus)

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 languageEnglish
Pages (from-to)1186-1201
Number of pages16
JournalStem Cells
Volume26
Issue number5
DOIs
Publication statusPublished - May 2008
Externally publishedYes

Fingerprint

Hematopoietic Stem Cells
Transcriptome
Adult Stem Cells
Genes
Stem Cells
Neural Stem Cells
Mesenchymal Stromal Cells
Endothelial Cells
Regenerative Medicine
Stem Cell Transplantation
Embryonic Stem Cells
Blood Cells

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 journalArticle

Huang, TS, Hsieh, JY, Wu, YH, Jen, CH, Tsuang, YH, Chiou, SH, Partanen, J, Anderson, H, Jaatinen, T, Yu, YH & Wang, HW 2008, 'Functional network reconstruction reveals somatic stemness genetic maps and dedifferentiation-like transcriptome reprogramming induced by GATA2', Stem Cells, vol. 26, no. 5, pp. 1186-1201. https://doi.org/10.1634/stemcells.2007-0821
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. / Functional network reconstruction reveals somatic stemness genetic maps and dedifferentiation-like transcriptome reprogramming induced by GATA2. In: Stem Cells. 2008 ; Vol. 26, No. 5. pp. 1186-1201.
@article{a571145d1f204bd48b2f4da53c2c06d3,
title = "Functional network reconstruction reveals somatic stemness genetic maps and dedifferentiation-like transcriptome reprogramming induced by GATA2",
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.",
keywords = "CD133 stem cell, Dedifferentiation, GATA2, Somatic stem cell, Systems biology",
author = "Huang, {Tse Shun} and Hsieh, {Jui Yu} and Wu, {Yu Hsuan} and Jen, {Chih Hung} and Tsuang, {Yang Hwei} and Chiou, {Shih Hwa} and Jukka Partanen and Heidi Anderson and Taina Jaatinen and Yu, {Yau Hua} and Wang, {Hsei Wei}",
year = "2008",
month = "5",
doi = "10.1634/stemcells.2007-0821",
language = "English",
volume = "26",
pages = "1186--1201",
journal = "Stem Cells",
issn = "1066-5099",
publisher = "AlphaMed Press",
number = "5",

}

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 -