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Clonal analysis of lineage fate in native haematopoiesis
Open accessAbstract
Haematopoiesis, the process of mature blood and immune cell production, is functionally organized as a hierarchy, with self-renewing haematopoietic stem cells and multipotent progenitor cells sitting at the very top. Multiple models have been proposed as to what the earliest lineage choices are in these primitive haematopoietic compartments, the cellular intermediates, and the resulting lineage trees that emerge from them. Given that the bulk of studies addressing lineage outcomes have been performed in the context of haematopoietic transplantation, current models of lineage branching are more likely to represent roadmaps of lineage potential than native fate. Here we use transposon tagging to clonally trace the fates of progenitors and stem cells in unperturbed haematopoiesis. Our results describe a distinct clonal roadmap in which the megakaryocyte lineage arises largely independently of other haematopoietic fates. Our data, combined with single-cell RNA sequencing, identify a functional hierarchy of unilineage- and oligolineage-producing clones within the multipotent progenitor population. Finally, our results demonstrate that traditionally defined long-term haematopoietic stem cells are a significant source of megakaryocyte-restricted progenitors, suggesting that the megakaryocyte lineage is the predominant native fate of long-term haematopoietic stem cells. Our study provides evidence for a substantially revised roadmap for unperturbed haematopoiesis, and highlights unique properties of multipotent progenitors and haematopoietic stem cells in situ.
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“Finally, while single-cell genomic approaches have produced compelling evidence that observed cellular heterogeneity reflects downstream lineage decisions (Herring et al., 2018; La Manno et al., 2018; Rodriguez-Fraticelli et al., 2018), in the absence of fate tracking, all inferred biases in native hematopoiesis are speculative (Pina et al., 2012; Velten et al., 2017).”
From Unraveling Hematopoiesis through the Lens of Genomics (2020) · cites this paper as Rodriguez-Fraticelli et al., 2018
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“Direct genetic barcoding in HSCs has also resulted in similar findings (Rodriguez-Fraticelli et al., 2018).”
From Unraveling Hematopoiesis through the Lens of Genomics (2020) · cites this paper as Rodriguez-Fraticelli et al., 2018
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Metadata
- Authors
- Rodriguez-Fraticelli, A. E., Wolock, S. L., Weinreb, C. S., Panero, R., Patel, S. H., Jankovic, M., Sun, J., Calogero, R. A., Klein, A. M., & Camargo, F. D.
- Affiliations
- Boston Children's Hospital (US)
- Harvard University (US)
- University of Turin (IT)
- Corresponding author
- Camargo, Fernando D.
- ORCID
- Venue
- Nature
- Published
- 2018-01
- Volume
- 553
- Issue
- 7687
- Pages
- 212-216
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC5884107
- OpenAlex
- W2781886817
- Cited by
- 596
- References
- 39
- Citations by year
- 2026: 41 · 2025: 70 · 2024: 76 · 2023: 56 · 2022: 75 · 2021: 76 · 2020: 91 · 2019: 68 · 2018: 43
- FWCI
- 49.81
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Institutional Research Information System University of Turin (University of Turin) (submittedVersion, other-oa)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- Howard Hughes Medical Institute
- Leukemia and Lymphoma Society
- Life Sciences Research Foundation
- National Institutes of Health (P01HL13147)
- National Heart, Lung, and Blood Institute (R01HL128850, P01HL131477)
- National Institute of General Medical Sciences (T32GM080177)
- National Institute of Diabetes and Digestive and Kidney Diseases (U54DK110805, P30DK034854)
- Topics
- Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
- Health Sciences › Medicine › Hematology › Acute Myeloid Leukemia Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Mesenchymal stem cell research
- Keywords
- hematopoiesis, hematopoietic stem cells, multipotent progenitors, clonal tracing, transposon tagging, megakaryocyte lineage, single-cell transcriptomics, megakaryopoiesis
- MeSH terms
- Animals, Clone Cells, Female, Hematopoiesis, Hematopoietic Stem Cells, Male, Megakaryocytes, Sequence Analysis, RNA, Cell Lineage, Multipotent Stem Cells, Mice, Single-Cell Analysis, Transcriptome
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