Transcriptional variability accelerates preleukemia by cell diversification and perturbation of protein synthesis Article Swipe
Shikha Gupta
,
Oliver M. Dovey
,
Ana Filipa Domingues
,
Oliwia W. Cyran
,
Caitlin M. Cash
,
George Giotopoulos
,
Justyna Rak
,
Jonathan Cooper
,
Malgorzata Gozdecka
,
Liza Dijkhuis
,
Ryan Asby
,
Noor Al-Jabery
,
Víctor Hernández-Hernández
,
Sudhakaran Prabakaran
,
Brian J.P. Huntly
,
George S. Vassiliou
,
Cristina Pina
·
YOU?
·
· 2022
· Open Access
·
· DOI: https://doi.org/10.1126/sciadv.abn4886
YOU?
·
· 2022
· Open Access
·
· DOI: https://doi.org/10.1126/sciadv.abn4886
Transcriptional variability facilitates stochastic cell diversification and can in turn underpin adaptation to stress or injury. We hypothesize that it may analogously facilitate progression of premalignancy to cancer. To investigate this, we initiated preleukemia in mouse cells with enhanced transcriptional variability due to conditional disruption of the histone lysine acetyltransferase gene Kat2a . By combining single-cell RNA sequencing of preleukemia with functional analysis of transformation, we show that Kat2a loss results in global variegation of cell identity and accumulation of preleukemic cells. Leukemia progression is subsequently facilitated by destabilization of ribosome biogenesis and protein synthesis, which confer a transient transformation advantage. The contribution of transcriptional variability to early cancer evolution reflects a generic role in promoting cell fate transitions, which, in the case of well-adapted malignancies, contrastingly differentiates and depletes cancer stem cells. That is, transcriptional variability confers forward momentum to cell fate systems, with differential multistage impact throughout cancer evolution.
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Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.1126/sciadv.abn4886
- OA Status
- gold
- Cited By
- 10
- References
- 47
- Related Works
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- OpenAlex ID
- https://openalex.org/W4289653559
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W4289653559Canonical identifier for this work in OpenAlex
- DOI
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https://doi.org/10.1126/sciadv.abn4886Digital Object Identifier
- Title
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Transcriptional variability accelerates preleukemia by cell diversification and perturbation of protein synthesisWork title
- Type
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articleOpenAlex work type
- Language
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enPrimary language
- Publication year
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2022Year of publication
- Publication date
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2022-08-03Full publication date if available
- Authors
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Shikha Gupta, Oliver M. Dovey, Ana Filipa Domingues, Oliwia W. Cyran, Caitlin M. Cash, George Giotopoulos, Justyna Rak, Jonathan Cooper, Malgorzata Gozdecka, Liza Dijkhuis, Ryan Asby, Noor Al-Jabery, Víctor Hernández-Hernández, Sudhakaran Prabakaran, Brian J.P. Huntly, George S. Vassiliou, Cristina PinaList of authors in order
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https://doi.org/10.1126/sciadv.abn4886Publisher landing page
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YesWhether a free full text is available
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goldOpen access status per OpenAlex
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https://doi.org/10.1126/sciadv.abn4886Direct OA link when available
- Concepts
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Preleukemia, Diversification (marketing strategy), Computational biology, Biology, Cell biology, Genetics, Leukemia, Marketing, BusinessTop concepts (fields/topics) attached by OpenAlex
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10Total citation count in OpenAlex
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2024: 9, 2023: 1Per-year citation counts (last 5 years)
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47Number of works referenced by this work
- Related works (count)
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10Other works algorithmically related by OpenAlex
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