Clonal dynamics of native haematopoiesis

Jianlong Sun, Azucena Ramos, Brad Chapman, Jonathan B. Johnnidis, Linda Le, Yu-Jui Ho, Allon Klein, Oliver Hofmann and Fernando D. Camargo ()
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Jianlong Sun: Stem Cell Program, Children’s Hospital
Azucena Ramos: Stem Cell Program, Children’s Hospital
Brad Chapman: Harvard School of Public Health
Jonathan B. Johnnidis: University of Pennsylvania
Linda Le: Stem Cell Program, Children’s Hospital
Yu-Jui Ho: Watson School of Biological Sciences, Cold Spring Harbor Laboratory
Allon Klein: Harvard Medical School
Oliver Hofmann: Harvard School of Public Health
Fernando D. Camargo: Stem Cell Program, Children’s Hospital

Nature, 2014, vol. 514, issue 7522, 322-327

Abstract: Abstract 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.

Date: 2014
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DOI: 10.1038/nature13824

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