Proteomic and functional comparison between human induced and embryonic stem cells Article Swipe
Alejandro J. Brenes
,
Eva Griesser
,
Linda V. Sinclair
,
L. S. P. Davidson
,
Alan R. Prescott
,
François Singh
,
Elizabeth Hogg
,
Carmen Espejo-Serrano
,
Hao Jiang
,
Harunori Yoshikawa
,
Melpomeni Platani
,
Jason R. Swedlow
,
Greg M. Findlay
,
Doreen A. Cantrell
,
Angus I. Lamond
·
YOU?
·
· 2021
· Open Access
·
· DOI: https://doi.org/10.1101/2021.10.20.464767
YOU?
·
· 2021
· Open Access
·
· DOI: https://doi.org/10.1101/2021.10.20.464767
Human induced pluripotent stem cells (hiPSCs) have great potential to be used as alternatives to embryonic stem cells (hESCs) in regenerative medicine and disease modelling, thereby avoiding many of the ethical issues arising from the use of embryo-derived cells. However, despite clear similarities between the two cell types, it is likely they are not identical. In this study, we characterise the proteomes of multiple hiPSC and hESC lines derived from independent donors. We find that while hESCs and hiPSCs express a near identical set of proteins, they show consistent quantitative differences in the expression levels of a wide subset of proteins. hiPSCs have increased total protein content, while maintaining a comparable cell cycle profile to hESCs. The proteomic data show hiPSCs have significantly increased abundance of vital cytoplasmic and mitochondrial proteins required to sustain high growth rates, including nutrient transporters and metabolic proteins, which correlated with phenotypic differences between hiPSCs and hESCs. Thus, higher levels of glutamine transporters correlated with increased glutamine uptake, while higher levels of proteins involved in lipid synthesis correlated with increased lipid droplet formation. Some of the biggest metabolic changes were seen in proteins involved in mitochondrial metabolism, with corresponding enhanced mitochondrial potential, shown experimentally using high-resolution respirometry. hiPSCs also produced higher levels of secreted proteins, including ECM components and growth factors, some with known tumorigenic properties, as well as proteins involved in the inhibition of the immune system. Our data indicate that reprogramming of human fibroblasts to iPSCs effectively restores protein expression in cell nuclei to a state comparable to hESCs, but does not similarly restore the profile of cytoplasmic and mitochondrial proteins, with consequences for cell phenotypes affecting growth and metabolism. The data improve understanding of the molecular differences between induced and embryonic stem cells, with implications for potential risks and benefits for their use in future disease modelling and therapeutic applications.
Related Topics
Concepts
Biology
Embryonic stem cell
Cell biology
Induced pluripotent stem cell
Proteome
Transcriptome
Reprogramming
Glutamine
Lipid droplet
Cell
Biochemistry
Gene expression
Gene
Amino acid
Metadata
- Type
- preprint
- Language
- en
- Landing Page
- https://doi.org/10.1101/2021.10.20.464767
- https://www.biorxiv.org/content/biorxiv/early/2021/10/20/2021.10.20.464767.full.pdf
- OA Status
- green
- References
- 92
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W3207756245
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W3207756245Canonical identifier for this work in OpenAlex
- DOI
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https://doi.org/10.1101/2021.10.20.464767Digital Object Identifier
- Title
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Proteomic and functional comparison between human induced and embryonic stem cellsWork title
- Type
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preprintOpenAlex work type
- Language
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enPrimary language
- Publication year
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2021Year of publication
- Publication date
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2021-10-20Full publication date if available
- Authors
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Alejandro J. Brenes, Eva Griesser, Linda V. Sinclair, L. S. P. Davidson, Alan R. Prescott, François Singh, Elizabeth Hogg, Carmen Espejo-Serrano, Hao Jiang, Harunori Yoshikawa, Melpomeni Platani, Jason R. Swedlow, Greg M. Findlay, Doreen A. Cantrell, Angus I. LamondList of authors in order
- Landing page
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https://doi.org/10.1101/2021.10.20.464767Publisher landing page
- PDF URL
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https://www.biorxiv.org/content/biorxiv/early/2021/10/20/2021.10.20.464767.full.pdfDirect link to full text PDF
- Open access
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YesWhether a free full text is available
- OA status
-
greenOpen access status per OpenAlex
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https://www.biorxiv.org/content/biorxiv/early/2021/10/20/2021.10.20.464767.full.pdfDirect OA link when available
- Concepts
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Biology, Embryonic stem cell, Cell biology, Induced pluripotent stem cell, Proteome, Transcriptome, Reprogramming, Glutamine, Lipid droplet, Cell, Biochemistry, Gene expression, Gene, Amino acidTop concepts (fields/topics) attached by OpenAlex
- Cited by
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0Total citation count in OpenAlex
- References (count)
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92Number of works referenced by this work
- Related works (count)
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10Other works algorithmically related by OpenAlex
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