Adaptation toex vivoculture drives human haematopoietic stem cell loss of repopulation capacity in a cell cycle independent manner Article Swipe
Carys Johnson
,
Kendig Sham
,
Serena Belluschi
,
Xiaonan Wang
,
Winnie Lau
,
Kerstin B. Kaufmann
,
Gabriela Krivdova
,
Emily F. Calderbank
,
Nicole Mende
,
Jessica McLeod
,
Giovanna Mantica
,
Matthew Williams
,
Charlotte Grey-Wilson
,
Michael Drakopoulos
,
Shubhankar Sinha
,
Evangelia Diamanti
,
Christina Basford
,
Anthony R. Green
,
Nicola K. Wilson
,
Steven J. Howe
,
John E. Dick
,
Berthold Göttgens
,
Natalie Francis
,
Elisa Laurenti
·
YOU?
·
· 2022
· Open Access
·
· DOI: https://doi.org/10.1101/2022.11.17.516906
YOU?
·
· 2022
· Open Access
·
· DOI: https://doi.org/10.1101/2022.11.17.516906
Loss of long-term haematopoietic stem cell function (LT-HSC) hampers the success of ex vivo HSC gene therapy and expansion procedures, but the kinetics and the mechanisms by which this occurs remain incompletely characterized. Here through time-resolved scRNA-Seq, matched in vivo functional analysis and the use of a reversible in vitro system of early G 1 arrest, we define the sequence of transcriptional and functional events occurring during the first ex vivo division of human LT-HSCs. We demonstrate that contrary to current assumptions, loss of long-term repopulation capacity during culture is independent of cell cycle progression. Instead it is a rapid event that follows an early period of adaptation to culture, characterised by transient gene expression dynamics and constrained global variability in gene expression. Cell cycle progression however contributes to the establishment of differentiation programmes in culture. Our data have important implications for improving HSC gene therapy and expansion protocols.
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Metadata
- Type
- preprint
- Language
- en
- Landing Page
- https://doi.org/10.1101/2022.11.17.516906
- https://www.biorxiv.org/content/biorxiv/early/2023/01/07/2022.11.17.516906.full.pdf
- OA Status
- green
- Cited By
- 1
- References
- 80
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4309407667
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W4309407667Canonical identifier for this work in OpenAlex
- DOI
-
https://doi.org/10.1101/2022.11.17.516906Digital Object Identifier
- Title
-
Adaptation toex vivoculture drives human haematopoietic stem cell loss of repopulation capacity in a cell cycle independent mannerWork title
- Type
-
preprintOpenAlex work type
- Language
-
enPrimary language
- Publication year
-
2022Year of publication
- Publication date
-
2022-11-17Full publication date if available
- Authors
-
Carys Johnson, Kendig Sham, Serena Belluschi, Xiaonan Wang, Winnie Lau, Kerstin B. Kaufmann, Gabriela Krivdova, Emily F. Calderbank, Nicole Mende, Jessica McLeod, Giovanna Mantica, Matthew Williams, Charlotte Grey-Wilson, Michael Drakopoulos, Shubhankar Sinha, Evangelia Diamanti, Christina Basford, Anthony R. Green, Nicola K. Wilson, Steven J. Howe, John E. Dick, Berthold Göttgens, Natalie Francis, Elisa LaurentiList of authors in order
- Landing page
-
https://doi.org/10.1101/2022.11.17.516906Publisher landing page
- PDF URL
-
https://www.biorxiv.org/content/biorxiv/early/2023/01/07/2022.11.17.516906.full.pdfDirect link to full text PDF
- Open access
-
YesWhether a free full text is available
- OA status
-
greenOpen access status per OpenAlex
- OA URL
-
https://www.biorxiv.org/content/biorxiv/early/2023/01/07/2022.11.17.516906.full.pdfDirect OA link when available
- Concepts
-
Haematopoiesis, Biology, Ex vivo, Stem cell, Cell biology, Cell cycle, Regeneration (biology), Immunology, Cancer research, In vivo, Gene, GeneticsTop concepts (fields/topics) attached by OpenAlex
- Cited by
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1Total citation count in OpenAlex
- Citations by year (recent)
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2023: 1Per-year citation counts (last 5 years)
- References (count)
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80Number of works referenced by this work
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10Other works algorithmically related by OpenAlex
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