Diverse and heritable lineage imprinting of early haematopoietic progenitors
Top Cited Papers
- 3 April 2013
- journal article
- research article
- Published by Springer Science and Business Media LLC in Nature
- Vol. 496 (7444), 229-232
- https://doi.org/10.1038/nature12013
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.This publication has 28 references indexed in Scilit:
- Mapping the life histories of T cellsNature Reviews Immunology, 2010
- Recruitment of Antigen-Specific CD8 + T Cells in Response to Infection Is Markedly EfficientScience, 2009
- Dissecting T cell lineage relationships by cellular barcodingThe Journal of Experimental Medicine, 2008
- Evolving views on the genealogy of B cellsNature Reviews Immunology, 2008
- Reciprocal Activation of GATA-1 and PU.1 Marks Initial Specification of Hematopoietic Stem Cells into Myeloerythroid and Myelolymphoid LineagesCell Stem Cell, 2007
- New Evidence Supporting Megakaryocyte-Erythrocyte Potential of Flk2/Flt3+ Multipotent Hematopoietic ProgenitorsCell, 2006
- Lineage Promiscuity and Plasticity in Hematopoietic DevelopmentAnnals of the New York Academy of Sciences, 2005
- Transcription from the RAG1 Locus Marks the Earliest Lymphocyte Progenitors in Bone MarrowImmunity, 2002
- Myeloid or Lymphoid Promiscuity as a Critical Step in Hematopoietic Lineage CommitmentDevelopmental Cell, 2002
- What We Have Learned from Retroviral Marking of Hematopoietic Stem CellsPublished by Springer Science and Business Media LLC ,1992