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Diverse and heritable lineage imprinting of early haematopoietic progenitors
Abstract
Haematopoietic stem cells (HSCs) and their subsequent progenitors produce blood cells, but the precise nature and kinetics of this production is a contentious issue. In one model, lymphoid and myeloid production branch after the lymphoid-primed multipotent progenitor (LMPP), with both branches subsequently producing dendritic cells. However, this model is based mainly on in vitro clonal assays and population-based tracking in vivo, which could miss in vivo single-cell complexity. Here we avoid these issues by using a new quantitative version of 'cellular barcoding' to trace the in vivo fate of hundreds of LMPPs and HSCs at the single-cell level. These data demonstrate that LMPPs are highly heterogeneous in the cell types that they produce, separating into combinations of lymphoid-, myeloid- and dendritic-cell-biased producers. Conversely, although we observe a known lineage bias of some HSCs, most cellular output is derived from a small number of HSCs that each generates all cell types. Crucially, in vivo analysis of the output of sibling cells derived from single LMPPs shows that they often share a similar fate, suggesting that the fate of these progenitors was imprinted. Furthermore, as this imprinting is also observed for dendritic-cell-biased LMPPs, dendritic cells may be considered a distinct lineage on the basis of separate ancestry. These data suggest a 'graded commitment' model of haematopoiesis, in which heritable and diverse lineage imprinting occurs earlier than pr…
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“More recently, genetic barcoding compatible with single-cell RNA sequencing (scRNA-seq) has provided information on the cellular output of hundreds of stem cell clones together with cell-state information on the stem cell itself8–12.”
From Clonal tracing with somatic epimutations reveals dynamics of blood ageing (2025) · cites this paper as [9]
In the citing paper
“Similar approaches, including paired daughter cell assays (Suda et al, 1984;Suda et al, 1984;Leary et al, 1985;Ema et al, 2005;Kent et al, 2008;Weinreb et al, 2020;Wehling et al, 2022) and HSPC split cultures (Benveniste et al, 2010;Naik et al, 2013;Lin et al, 2018;Tian et al, 2021) have been restricted to clonal tracking for describing cellular or molecular outputs, assuming substantial uniform”
From A scalable in vitro cell competition model identifies preleukemic super competitor clones (2026) · cites this paper as Naik et al, 2013
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Metadata
- Authors
- Naik, S. H., Perié, L., Swart, E., Gerlach, C., van Rooij, N., de Boer, R. J., & Schumacher, T. N.
- Venue
- Nature
- Published
- 2013-04
- Volume
- 496
- Issue
- 7444
- Pages
- 229-232
- ISSN
- 0028-0836
- 1476-4687
- Cited by
- 408
- References
- 1
- Language
- en
- Licence
- www.springer.com/tdm (tdm)
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