Diverse and heritable lineage imprinting of early haematopoietic progenitors
- Author(s)
- Naik, SH; Perie, L; Swart, E; Gerlach, C; van Rooij, N; de Boer, RJ; Schumacher, TN;
- Details
- Publication Year 2013-04-11,Volume 496,Issue #7444,Page 229-+
- Journal Title
- NATURE
- Publication Type
- Journal Article
- 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)(1), with both branches subsequently producing dendritic cells(2). 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(3-7). Here we avoid these issues by using a new quantitative version of 'cellular barcoding'(8-10) 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 HSCs11-14, 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 previously thought.
- Publisher
- NATURE PUBLISHING GROUP
- Keywords
- DENDRITIC-CELL-DEVELOPMENT; STEM-CELLS; IN-VIVO; T-CELLS; COMMITMENT; SUBTYPES; PROMISCUITY; COMPARTMENT; SUBSETS; SYSTEM
- Research Division(s)
- Immunology
- Publisher's Version
- https://doi.org/10.1038/nature12013
- Terms of Use/Rights Notice
- © 2013 Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved.
Creation Date: 2013-04-11 12:00:00