Single-Cell Proteomics Reveal that Quantitative Changes in Co-expressed Lineage-Specific Transcription Factors Determine Cell Fate
Open accessAbstract
Hematopoiesis provides an accessible system for studying the principles underlying cell-fate decisions in stem cells. Proposed models of hematopoiesis suggest that quantitative changes in lineage-specific transcription factors (LS-TFs) underlie cell-fate decisions. However, evidence for such models is lacking as TF levels are typically measured via RNA expression rather than by analyzing temporal changes in protein abundance. Here, we used single-cell mass cytometry and absolute quantification by mass spectrometry to capture the temporal dynamics of TF protein expression in individual cells during human erythropoiesis. We found that LS-TFs from alternate lineages are co-expressed, as proteins, in individual early progenitor cells and quantitative changes of LS-TFs occur gradually rather than abruptly to direct cell-fate decisions. Importantly, upregulation of a megakaryocytic TF in early progenitors is sufficient to deviate cells from an erythroid to a megakaryocyte trajectory, showing that quantitative changes in protein abundance of LS-TFs in progenitors can determine alternate cell fates.
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Single-cell proteomics methods contribute to understanding how protein levels change during differentiation by analysing lineage-specific transcription factors.
“Single-cell proteomics methods contribute to our understanding of how protein levels change as cells differentiate by analysing lineage-specific transcription factors and their abundance over time, ultimately leading to the maintenance or emergence of a lineage trajectory139.”
From The technological landscape and applications of single-cell multi-omics (2023) · cites this paper as [139]
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- Authors
- Palii, C. G., Cheng, Q., Gillespie, M. A., Shannon, P., Mazurczyk, M., Napolitani, G., Price, N. D., Ranish, J. A., Morrissey, E., Higgs, D. R., & Brand, M.
- Affiliations
- University of Ottawa (CA)
- John Radcliffe Hospital (GB)
- Institute for Systems Biology (US)
- Corresponding author
- Morrissey, Edward
- Higgs, Douglas R.
- Brand, Marjorie
- ORCID
- Venue
- Cell Stem Cell
- Publisher
- Elsevier BV
- Published
- 2019-05
- Volume
- 24
- Issue
- 5
- Pages
- 812-820.e5
- ISSN
- 1875-9777 (ISSN-L)
- 1934-5909
- PMC
- PMC6886472
- OpenAlex
- W2922486000
- Cited by
- 148
- References
- 36
- Citations by year
- 2026: 14 · 2025: 21 · 2024: 19 · 2023: 16 · 2022: 12 · 2021: 22 · 2020: 29 · 2019: 13 · 2018: 1
- FWCI
- 13.43
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell stem cell (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (1R01DK098449-01A1)
- Research Councils UK (MC_UU_12025 /, MC_UU_12009/4)
- NIHR Oxford Biomedical Research Centre
- Topics
- Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
- Physical Sciences › Chemistry › Spectroscopy › Advanced Proteomics Techniques and Applications
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Single-cell and spatial transcriptomics
- Keywords
- hematopoiesis, cell fate determination, lineage-specific transcription factors, erythropoiesis, megakaryopoiesis, hematopoietic progenitor cells, single-cell mass cytometry, absolute protein quantification
- MeSH terms
- Cell Differentiation, Cells, Cultured, Erythropoiesis, Gene Expression Regulation, Hematopoiesis, Hematopoietic Stem Cells, Humans, Mass Spectrometry, Transcription Factors, Umbilical Cord, Transcriptional Activation, Antigens, CD34, Cell Lineage, Proteomics, Single-Cell Analysis
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