A mouse embryonic stem cell bank for inducible overexpression of human chromosome 21 genes

Rossella De Cegli, Antonio Romito, Simona Iacobacci, Lei Mao, Mario Lauria, Anthony O. Fedele, Joachim Klose, Christelle Borel, Patrick Descombes, Stylianos E. Antonarakis, Diego di Bernardo, Sandro Banfi, Andrea Ballabio, Gilda Cobellis

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Background: Dosage imbalance is responsible for several genetic diseases, among which Down syndrome is caused by the trisomy of human chromosome 21.Results: To elucidate the extent to which the dosage imbalance of specific human chromosome 21 genes perturb distinct molecular pathways, we developed the first mouse embryonic stem (ES) cell bank of human chromosome 21 genes. The human chromosome 21-mouse ES cell bank includes, in triplicate clones, 32 human chromosome 21 genes, which can be overexpressed in an inducible manner. Each clone was transcriptionally profiled in inducing versus non-inducing conditions. Analysis of the transcriptional response yielded results that were consistent with the perturbed gene's known function. Comparison between mouse ES cells containing the whole human chromosome 21 (trisomic mouse ES cells) and mouse ES cells overexpressing single human chromosome 21 genes allowed us to evaluate the contribution of single genes to the trisomic mouse ES cell transcriptome. In addition, for the clones overexpressing the Runx1 gene, we compared the transcriptome changes with the corresponding protein changes by mass spectroscopy analysis.Conclusions: We determined that only a subset of genes produces a strong transcriptional response when overexpressed in mouse ES cells and that this effect can be predicted taking into account the basal gene expression level and the protein secondary structure. We showed that the human chromosome 21-mouse ES cell bank is an important resource, which may be instrumental towards a better understanding of Down syndrome and other human aneuploidy disorders.

LanguageEnglish
Article numberR64
JournalGenome Biology
Volume11
Issue number6
DOIs
Publication statusPublished - 22 Jun 2010

ASJC Scopus subject areas

  • Ecology, Evolution, Behavior and Systematics
  • Genetics
  • Cell Biology

Cite this

De Cegli, Rossella ; Romito, Antonio ; Iacobacci, Simona ; Mao, Lei ; Lauria, Mario ; Fedele, Anthony O. ; Klose, Joachim ; Borel, Christelle ; Descombes, Patrick ; Antonarakis, Stylianos E. ; di Bernardo, Diego ; Banfi, Sandro ; Ballabio, Andrea ; Cobellis, Gilda. / A mouse embryonic stem cell bank for inducible overexpression of human chromosome 21 genes. In: Genome Biology. 2010 ; Vol. 11, No. 6.
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abstract = "Background: Dosage imbalance is responsible for several genetic diseases, among which Down syndrome is caused by the trisomy of human chromosome 21.Results: To elucidate the extent to which the dosage imbalance of specific human chromosome 21 genes perturb distinct molecular pathways, we developed the first mouse embryonic stem (ES) cell bank of human chromosome 21 genes. The human chromosome 21-mouse ES cell bank includes, in triplicate clones, 32 human chromosome 21 genes, which can be overexpressed in an inducible manner. Each clone was transcriptionally profiled in inducing versus non-inducing conditions. Analysis of the transcriptional response yielded results that were consistent with the perturbed gene's known function. Comparison between mouse ES cells containing the whole human chromosome 21 (trisomic mouse ES cells) and mouse ES cells overexpressing single human chromosome 21 genes allowed us to evaluate the contribution of single genes to the trisomic mouse ES cell transcriptome. In addition, for the clones overexpressing the Runx1 gene, we compared the transcriptome changes with the corresponding protein changes by mass spectroscopy analysis.Conclusions: We determined that only a subset of genes produces a strong transcriptional response when overexpressed in mouse ES cells and that this effect can be predicted taking into account the basal gene expression level and the protein secondary structure. We showed that the human chromosome 21-mouse ES cell bank is an important resource, which may be instrumental towards a better understanding of Down syndrome and other human aneuploidy disorders.",
author = "{De Cegli}, Rossella and Antonio Romito and Simona Iacobacci and Lei Mao and Mario Lauria and Fedele, {Anthony O.} and Joachim Klose and Christelle Borel and Patrick Descombes and Antonarakis, {Stylianos E.} and {di Bernardo}, Diego and Sandro Banfi and Andrea Ballabio and Gilda Cobellis",
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De Cegli, R, Romito, A, Iacobacci, S, Mao, L, Lauria, M, Fedele, AO, Klose, J, Borel, C, Descombes, P, Antonarakis, SE, di Bernardo, D, Banfi, S, Ballabio, A & Cobellis, G 2010, 'A mouse embryonic stem cell bank for inducible overexpression of human chromosome 21 genes', Genome Biology, vol. 11, no. 6, R64. https://doi.org/10.1186/gb-2010-11-6-r64

A mouse embryonic stem cell bank for inducible overexpression of human chromosome 21 genes. / De Cegli, Rossella; Romito, Antonio; Iacobacci, Simona; Mao, Lei; Lauria, Mario; Fedele, Anthony O.; Klose, Joachim; Borel, Christelle; Descombes, Patrick; Antonarakis, Stylianos E.; di Bernardo, Diego; Banfi, Sandro; Ballabio, Andrea; Cobellis, Gilda.

In: Genome Biology, Vol. 11, No. 6, R64, 22.06.2010.

Research output: Contribution to journalArticle

TY - JOUR

T1 - A mouse embryonic stem cell bank for inducible overexpression of human chromosome 21 genes

AU - De Cegli, Rossella

AU - Romito, Antonio

AU - Iacobacci, Simona

AU - Mao, Lei

AU - Lauria, Mario

AU - Fedele, Anthony O.

AU - Klose, Joachim

AU - Borel, Christelle

AU - Descombes, Patrick

AU - Antonarakis, Stylianos E.

AU - di Bernardo, Diego

AU - Banfi, Sandro

AU - Ballabio, Andrea

AU - Cobellis, Gilda

PY - 2010/6/22

Y1 - 2010/6/22

N2 - Background: Dosage imbalance is responsible for several genetic diseases, among which Down syndrome is caused by the trisomy of human chromosome 21.Results: To elucidate the extent to which the dosage imbalance of specific human chromosome 21 genes perturb distinct molecular pathways, we developed the first mouse embryonic stem (ES) cell bank of human chromosome 21 genes. The human chromosome 21-mouse ES cell bank includes, in triplicate clones, 32 human chromosome 21 genes, which can be overexpressed in an inducible manner. Each clone was transcriptionally profiled in inducing versus non-inducing conditions. Analysis of the transcriptional response yielded results that were consistent with the perturbed gene's known function. Comparison between mouse ES cells containing the whole human chromosome 21 (trisomic mouse ES cells) and mouse ES cells overexpressing single human chromosome 21 genes allowed us to evaluate the contribution of single genes to the trisomic mouse ES cell transcriptome. In addition, for the clones overexpressing the Runx1 gene, we compared the transcriptome changes with the corresponding protein changes by mass spectroscopy analysis.Conclusions: We determined that only a subset of genes produces a strong transcriptional response when overexpressed in mouse ES cells and that this effect can be predicted taking into account the basal gene expression level and the protein secondary structure. We showed that the human chromosome 21-mouse ES cell bank is an important resource, which may be instrumental towards a better understanding of Down syndrome and other human aneuploidy disorders.

AB - Background: Dosage imbalance is responsible for several genetic diseases, among which Down syndrome is caused by the trisomy of human chromosome 21.Results: To elucidate the extent to which the dosage imbalance of specific human chromosome 21 genes perturb distinct molecular pathways, we developed the first mouse embryonic stem (ES) cell bank of human chromosome 21 genes. The human chromosome 21-mouse ES cell bank includes, in triplicate clones, 32 human chromosome 21 genes, which can be overexpressed in an inducible manner. Each clone was transcriptionally profiled in inducing versus non-inducing conditions. Analysis of the transcriptional response yielded results that were consistent with the perturbed gene's known function. Comparison between mouse ES cells containing the whole human chromosome 21 (trisomic mouse ES cells) and mouse ES cells overexpressing single human chromosome 21 genes allowed us to evaluate the contribution of single genes to the trisomic mouse ES cell transcriptome. In addition, for the clones overexpressing the Runx1 gene, we compared the transcriptome changes with the corresponding protein changes by mass spectroscopy analysis.Conclusions: We determined that only a subset of genes produces a strong transcriptional response when overexpressed in mouse ES cells and that this effect can be predicted taking into account the basal gene expression level and the protein secondary structure. We showed that the human chromosome 21-mouse ES cell bank is an important resource, which may be instrumental towards a better understanding of Down syndrome and other human aneuploidy disorders.

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U2 - 10.1186/gb-2010-11-6-r64

DO - 10.1186/gb-2010-11-6-r64

M3 - Article

VL - 11

JO - Genome biology

T2 - Genome biology

JF - Genome biology

SN - 1465-6906

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