Interactions between Notch- and hypoxia-induced transcriptomes in embryonic stem cells

Heather Main, Kian Leong Lee, Henry Yang, Saija Haapa-Paananen, Henrik Edgren, Shaobo Jin, Cecilia Sahlgren, Olli Kallioniemi, Lorenz Poellinger, Bing Lim (Corresponding Author), Urban Lendahl (Corresponding Author)

Research output: Contribution to journalArticleScientificpeer-review

26 Citations (Scopus)

Abstract

Interaction between key signaling mechanisms is important to generate the diversity in signaling output required for proper control of cellular differentiation and function, although the molecular manifestations of such cross-talk are only partially understood. Notch signaling and the cellular response to hypoxia intersect at different points in the signaling cascades, and in this report we analyze the consequences of this cross-talk at the transcriptome level. Mouse ES cells were subjected to various combinations of hypoxia and/or activated Notch signaling, and the transcriptome changes could be grouped into different categories, reflecting various modes of hypoxia and Notch signaling integration. Two principal categories of novel Notch- and hypoxia-induced genes were identified: (i) a larger set of Notch or hypoxic target genes which were induced by one pathway and not significantly affected by the activity status of the other pathway and (ii) a smaller set of genes co-regulated by Notch and hypoxia. In the latter category, we identified genes that were induced by hypoxia and the expression of which was enhanced by active Notch signaling and another group of genes that were induced by Notch and hypoxia independently. Several of the hypoxia- and Notch-induced genes were found to be upregulated in various forms of cancer. Identification of genes co-regulated by the two pathways may provide a molecular platform to better understand the intersection between the two signaling cascades in normal development and cancer.
Original languageEnglish
Pages (from-to)1610-1624
JournalExperimental Cell Research
Volume316
Issue number9
DOIs
Publication statusPublished - 2010
MoE publication typeA1 Journal article-refereed

Fingerprint

Embryonic Stem Cells
Transcriptome
Genes
Hypoxia
Neoplasms

Keywords

  • Micro-array
  • Transcriptome
  • Gamma secretase
  • HIF
  • FIH
  • CSL
  • ES cell

Cite this

Main, H., Lee, K. L., Yang, H., Haapa-Paananen, S., Edgren, H., Jin, S., ... Lendahl, U. (2010). Interactions between Notch- and hypoxia-induced transcriptomes in embryonic stem cells. Experimental Cell Research, 316(9), 1610-1624. https://doi.org/10.1016/j.yexcr.2009.12.012
Main, Heather ; Lee, Kian Leong ; Yang, Henry ; Haapa-Paananen, Saija ; Edgren, Henrik ; Jin, Shaobo ; Sahlgren, Cecilia ; Kallioniemi, Olli ; Poellinger, Lorenz ; Lim, Bing ; Lendahl, Urban. / Interactions between Notch- and hypoxia-induced transcriptomes in embryonic stem cells. In: Experimental Cell Research. 2010 ; Vol. 316, No. 9. pp. 1610-1624.
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Main, H, Lee, KL, Yang, H, Haapa-Paananen, S, Edgren, H, Jin, S, Sahlgren, C, Kallioniemi, O, Poellinger, L, Lim, B & Lendahl, U 2010, 'Interactions between Notch- and hypoxia-induced transcriptomes in embryonic stem cells', Experimental Cell Research, vol. 316, no. 9, pp. 1610-1624. https://doi.org/10.1016/j.yexcr.2009.12.012

Interactions between Notch- and hypoxia-induced transcriptomes in embryonic stem cells. / Main, Heather; Lee, Kian Leong; Yang, Henry; Haapa-Paananen, Saija; Edgren, Henrik; Jin, Shaobo; Sahlgren, Cecilia; Kallioniemi, Olli; Poellinger, Lorenz; Lim, Bing (Corresponding Author); Lendahl, Urban (Corresponding Author).

In: Experimental Cell Research, Vol. 316, No. 9, 2010, p. 1610-1624.

Research output: Contribution to journalArticleScientificpeer-review

TY - JOUR

T1 - Interactions between Notch- and hypoxia-induced transcriptomes in embryonic stem cells

AU - Main, Heather

AU - Lee, Kian Leong

AU - Yang, Henry

AU - Haapa-Paananen, Saija

AU - Edgren, Henrik

AU - Jin, Shaobo

AU - Sahlgren, Cecilia

AU - Kallioniemi, Olli

AU - Poellinger, Lorenz

AU - Lim, Bing

AU - Lendahl, Urban

PY - 2010

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N2 - Interaction between key signaling mechanisms is important to generate the diversity in signaling output required for proper control of cellular differentiation and function, although the molecular manifestations of such cross-talk are only partially understood. Notch signaling and the cellular response to hypoxia intersect at different points in the signaling cascades, and in this report we analyze the consequences of this cross-talk at the transcriptome level. Mouse ES cells were subjected to various combinations of hypoxia and/or activated Notch signaling, and the transcriptome changes could be grouped into different categories, reflecting various modes of hypoxia and Notch signaling integration. Two principal categories of novel Notch- and hypoxia-induced genes were identified: (i) a larger set of Notch or hypoxic target genes which were induced by one pathway and not significantly affected by the activity status of the other pathway and (ii) a smaller set of genes co-regulated by Notch and hypoxia. In the latter category, we identified genes that were induced by hypoxia and the expression of which was enhanced by active Notch signaling and another group of genes that were induced by Notch and hypoxia independently. Several of the hypoxia- and Notch-induced genes were found to be upregulated in various forms of cancer. Identification of genes co-regulated by the two pathways may provide a molecular platform to better understand the intersection between the two signaling cascades in normal development and cancer.

AB - Interaction between key signaling mechanisms is important to generate the diversity in signaling output required for proper control of cellular differentiation and function, although the molecular manifestations of such cross-talk are only partially understood. Notch signaling and the cellular response to hypoxia intersect at different points in the signaling cascades, and in this report we analyze the consequences of this cross-talk at the transcriptome level. Mouse ES cells were subjected to various combinations of hypoxia and/or activated Notch signaling, and the transcriptome changes could be grouped into different categories, reflecting various modes of hypoxia and Notch signaling integration. Two principal categories of novel Notch- and hypoxia-induced genes were identified: (i) a larger set of Notch or hypoxic target genes which were induced by one pathway and not significantly affected by the activity status of the other pathway and (ii) a smaller set of genes co-regulated by Notch and hypoxia. In the latter category, we identified genes that were induced by hypoxia and the expression of which was enhanced by active Notch signaling and another group of genes that were induced by Notch and hypoxia independently. Several of the hypoxia- and Notch-induced genes were found to be upregulated in various forms of cancer. Identification of genes co-regulated by the two pathways may provide a molecular platform to better understand the intersection between the two signaling cascades in normal development and cancer.

KW - Micro-array

KW - Transcriptome

KW - Gamma secretase

KW - HIF

KW - FIH

KW - CSL

KW - ES cell

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DO - 10.1016/j.yexcr.2009.12.012

M3 - Article

VL - 316

SP - 1610

EP - 1624

JO - Experimental Cell Research

JF - Experimental Cell Research

SN - 0014-4827

IS - 9

ER -