Clonal dynamics of native haematopoiesis

By Jianlong Sun, A. Ramos, Brad A. Chapman, Jonathan B. Johnnidis, Linda Le, Yu-jui Ho, Allon M. Klein, Oliver Hofmann, F. Camargo. Nature, 2014

751 citations recorded by the source corpus.

It is currently thought that life-long blood cell production is driven by the action of a small number of multipotent haematopoietic stem cells. Evidence supporting this view has been largely acquired through the use of functional assays involving transplantation. However, whether these mechanisms also govern native non-transplant haematopoiesis is entirely unclear. Here we have established a novel experimental model in mice where cells can be uniquely and genetically labelled in situ to address this question. Using this approach, we have performed longitudinal analyses of clonal dynamics in adult mice that reveal unprecedented features of native haematopoiesis. In contrast to what occurs following transplantation, steady-state blood production is maintained by the successive recruitment of thousands of clones, each with a minimal contribution to mature progeny. Our results demonstrate that a large number of long-lived progenitors, rather than classically defined haematopoietic stem cells, are the main drivers of steady-state haematopoiesis during most of adulthood. Our results also have implications for understanding the cellular origin of haematopoietic disease.

Subfields: Hematology, Immunology

View Paper: https://www.semanticscholar.org/paper/7b608874d3a8dd7f62eb039f2644336bf09fe35a

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Hematology

1. J. Dick
2. Steffen Jung
3. E. Laurenti
4. Florent Ginhoux
5. E. Passegué
6. A. Trumpp

In Immunology

1. A. Mildner
2. Florent Ginhoux
3. Steffen Jung
4. J. Dick
5. M. Guilliams
6. P. Italiani
7. D. Boraschi

Citations in the corpus

• Transcriptional Heterogeneity and Lineage Commitment in Myeloid Progenitors. (2015, background): “However, recent studies suggest that these assays should be taken with some caution, as they involve severe perturbation of the host hematopoietic niche structure and major systemic stress in the recipient (Sun et al., 2014).”
• Functionally distinct subsets of lineage-biased multipotent progenitors control blood production in normal and regenerative conditions (2015, positive): “However, all these models are interpretations of reconstitution patterns in transplanted mice, which are unlikely to reflect HSC function and lineage specification in native conditions as directly suggested by two recent lineage tracking studies that both showed a limited contribution of HSCs to ong”
• Lineage tracing on transcriptional landscapes links state to fate during differentiation (2018, methodology): “Third, in native hematopoiesis, we examined the clonal cooccurrence of Mos with DCs and Neus after genetically barcoding HPC clones in a nonperturbativemanner using a transposase-based strategy (22) (materials and methods, section 12.”
• Human haematopoietic stem cell lineage commitment is a continuous process (2017, positive): “…both information on the lineage potential of HSCs (index-culture) and insights into the unperturbed lineage commitment of HSCs during human haematopoiesis (reconstruction of developmental trajectories from static single cell expression data), where lineage tracing approaches 8,9 are not possible.”
• DISTINCT ROUTES OF LINEAGE DEVELOPMENT RESHAPE THE HUMAN BLOOD HIERARCHY ACROSS ONTOGENY (2015, background): “Recent HSC fate-mapping analyses in mice have provocatively shown that progenitors, but not HSCs, are fundamental for ongoing hematopoiesis under homeostatic conditions (27, 28).”