title: Clonal dynamics of native haematopoiesis.
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.
authors.affiliation: 1] Stem Cell Program, Children's Hospital, Boston, Massachusetts 02115, USA [2] Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, Massachusetts 02138, USA [3] Harvard Stem Cell Institute, Cambridge, Massachusetts 02138, USA.
authors.forename: Jianlong
authors.initials: J
authors.lastname: Sun
authors.affiliation: Stem Cell Program, Children's Hospital, Boston, Massachusetts 02115, USA.
authors.forename: Azucena
authors.initials: A
authors.lastname: Ramos
authors.affiliation: Department of Biostatistics, Harvard School of Public Health, Boston, Massachusetts 02115, USA.
authors.forename: Brad
authors.initials: B
authors.lastname: Chapman
authors.affiliation: Department of Immunology, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
authors.forename: Jonathan B
authors.initials: JB
authors.lastname: Johnnidis
authors.affiliation: Stem Cell Program, Children's Hospital, Boston, Massachusetts 02115, USA.
authors.forename: Linda
authors.initials: L
authors.lastname: Le
authors.affiliation: Watson School of Biological Sciences, Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, USA.
authors.forename: Yu-Jui
authors.initials: YJ
authors.lastname: Ho
authors.affiliation: Department of Systems Biology, Harvard Medical School, Boston, Massachusetts 02115, USA.
authors.forename: Allon
authors.initials: A
authors.lastname: Klein
authors.affiliation: Department of Biostatistics, Harvard School of Public Health, Boston, Massachusetts 02115, USA.
authors.forename: Oliver
authors.initials: O
authors.lastname: Hofmann
authors.affiliation: 1] Stem Cell Program, Children's Hospital, Boston, Massachusetts 02115, USA [2] Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, Massachusetts 02138, USA [3] Harvard Stem Cell Institute, Cambridge, Massachusetts 02138, USA.
authors.forename: Fernando D
authors.initials: FD
authors.lastname: Camargo
mesh_terms: D000818:Animals; D019070:Cell Lineage; D016922:Cellular Senescence; D002999:Clone Cells / Q000166:cytology* / Q000378:metabolism; D004251:DNA Transposable Elements / Q000235:genetics; D005260:Female; D005819:Genetic Markers / Q000235:genetics; D006410:Hematopoiesis; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000378:metabolism; D008297:Male; D051379:Mice; D038042:Myelopoiesis; D013194:Staining and Labeling; D013997:Time Factors
chemical_list: D004251:DNA Transposable Elements; D005819:Genetic Markers