Design principle of gene expression used by human stem cells: implication for pluripotency

Golan-Mashiach, Michal; Dazard, Jean-Eudes; Gerecht‐Nir, Sharon; Amariglio, Ninette; Fisher, Tamar; Jacob‐Hirsch, Jasmine; Bielorai, Bella; Osenberg, Sivan; Barad, Omer; Getz, Gad; Toren, Amos; Rechavi, Gideon; Itskovitz‐Eldor, Joseph; Domany, Eytan; Givol, David

doi:10.1096/fj.04-2417fje

Cited by 72 publications

(57 citation statements)

References 52 publications

(98 reference statements)

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“…When the authors discuss the reasons for the major differences between studies, they report that most genes in ESCs are expressed at very low levels, with 70% of them at less than 50 tpm, which would render them practically undetectable in hybridization microarrays, for example. This is compatible with another microarray study 30 and an additional MPSS study mentioned above, 18 which shows a total of 13,824 unique signatures in mouse ESCs, compared with 9,845 in EBs. The latter study also shows 20,027 (or 23,500 in another line) unique transcripts in human ESCs contrasted with 17,278 unique transcripts in human EBs.…”

Section: Evidence For Enhanced Global Transcription In Escsupporting

confidence: 89%

Stem cells do play with dice: A statistical physics view of transcription

Efroni

Melcer²,

Nissim-Rafinia³

et al. 2009

Cell Cycle

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Section: Evidence For Enhanced Global Transcription In Escsupporting

confidence: 89%

Stem cells do play with dice: A statistical physics view of transcription

Efroni

Melcer²,

Nissim-Rafinia³

et al. 2009

Cell Cycle

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“…This designed principle, named ''just-in-time'' (Zaslaver et al, 2004), is an energy-saving program that is apparently important for rapidly dividing organisms, but it requires highly accurate and stringent conservation of promoters during evolution. In contrast, human stem cells not only use a just-in-time program but also maintain a basal expression level of a large number of genes even in the absence of any cue, so that their gene products will be available ''just-in-case'' when they are needed (Golan-Mashiach et al, 2004;Domany, 2005). This strategy is energetically uneconomical but requires minimal transcriptional control, enabling the cells to have a diverse response to arriving cues, which is critical for their differentiation (Domany, 2005).…”

Section: A Hypothesis For a Two-component Module Regulating Plant Amimentioning

confidence: 99%

Principal Transcriptional Programs Regulating Plant Amino Acid Metabolism in Response to Abiotic Stresses

2008

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Using a bioinformatics analysis of public Arabidopsis (Arabidopsis thaliana) microarray data, we propose here a novel regulatory program, combining transcriptional and posttranslational controls, which participate in modulating fluxes of amino acid metabolism in response to abiotic stresses. The program includes the following two components: (1) the terminal enzyme of the module, responsible for the first catabolic step of the amino acid, whose level is stimulated or repressed in response to stress cues, just-in-time when the cues arrive, principally via transcriptional regulation of its gene; and (2) the initiator enzyme of the module, whose activity is principally modulated via posttranslational allosteric feedback inhibition in response to changes in the level of the amino acid, just-in-case when it occurs in response to alteration in its catabolism or sequestration into different intracellular compartments. Our proposed regulatory program is based on bioinformatics dissection of the response of all biosynthetic and catabolic genes of seven different pathways, involved in the metabolism of 11 amino acids, to eight different abiotic stresses, as judged from modulations of their mRNA levels. Our results imply that the transcription of the catabolic genes is principally more sensitive than that of the biosynthetic genes to fluctuations in stress-associated signals. Notably, the only exception to this program is the metabolic pathway of Pro, an amino acid that distinctively accumulates to significantly high levels under abiotic stresses. Examples of the biological significance of our proposed regulatory program are discussed.

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“…Embryonic stem cells seem to use the strategy to express genes representing various differentiation pathways. Upon differentiation, they select only a few for continuous expression [61]. Thus, the presence of proteins may be indicative for lack of differentiation or, vice versa, the absence of proteins may be typical for differentiated cells.…”

Section: Functional Classification Of Identified Proteins In Ucb-mscmentioning

confidence: 99%

Stem cell proteomes: A profile of human mesenchymal stem cells derived from umbilical cord blood

et al. 2005

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Multipotent mesenchymal stem cells (MSCs) derived from human umbilical cord blood (UCB) represent promising candidates for the development of future strategies in cellular therapy. To create a comprehensive protein expression profile for UCB-MSCs, one UCB unit from a full-term delivery was isolated from the unborn placenta, transferred into culture, and their whole-cell protein fraction was subjected to two-dimensional electrophoresis (2-DE). Unambiguous protein identification was achieved with peptide mass fingerprinting matrix-assisted laser desorption/ionization - time of flight - mass spectrometry (MALDI-TOF-MS), peptide sequencing (MALDI LIFT-TOF/TOF MS), as well as gel-matching with previously identified databases. In overall five replicate 2-DE runs, a total of 2037 +/- 437 protein spots were detected of which 205 were identified representing 145 different proteins and 60 isoforms or post-translational modifications. The identified proteins could be grouped into several functional categories, such as metabolism, folding, cytoskeleton, transcription, signal transduction, protein degradation, detoxification, vesicle/protein transport, cell cycle regulation, apoptosis, and calcium homeostasis. The acquired proteome map of nondifferentiated UCB-MSCs is a useful inventory which facilitates the identification of the normal proteomic pattern as well as its changes due to activated or suppressed pathways of cytosolic signal transduction which occur during proliferation, differentiation, or other experimental conditions.

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Design principle of gene expression used by human stem cells: implication for pluripotency

Cited by 72 publications

References 52 publications

Stem cells do play with dice: A statistical physics view of transcription

Stem cells do play with dice: A statistical physics view of transcription

Principal Transcriptional Programs Regulating Plant Amino Acid Metabolism in Response to Abiotic Stresses

Stem cell proteomes: A profile of human mesenchymal stem cells derived from umbilical cord blood

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