title: The Branching Point in Erythro-Myeloid Differentiation.
abstract: Development of mature blood cell progenies from hematopoietic stem cells involves the transition through lineage-restricted progenitors. The first branching point along this developmental process is thought to separate the erythro-myeloid and lymphoid lineage fate by yielding two intermediate progenitors, the common myeloid and the common lymphoid progenitors (CMPs and CLPs). Here, we use single-cell lineage tracing to demonstrate that so-called CMPs are highly heterogeneous with respect to cellular output, with most individual CMPs yielding either only erythrocytes or only myeloid cells after transplantation. Furthermore, based on the labeling of earlier progenitors, we show that the divergence between the myeloid and erythroid lineage develops within multipotent progenitors (MPP). These data provide evidence for a model of hematopoietic branching in which multiple distinct lineage commitments occur in parallel within the MPP pool.
authors.affiliation: Division of Immunology, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, the Netherlands; Theoretical Biology and Bioinformatics, Utrecht University, Padualaan 8, 3584 CH Utrecht, the Netherlands; Institut Curie, PSL Research University, CNRS UMR168, 26 rue d'Ulm, 75005 Paris, France; Sorbonne Universités, UPMC Univ Paris 06, 4 place Jussieu, 75005 Paris, France. Electronic address: leila.perie@curie.fr.
authors.forename: Leïla
authors.initials: L
authors.lastname: Perié
authors.affiliation: Hamilton Institute, Maynooth University, Maynooth, Co Kildare, Ireland.
authors.forename: Ken R
authors.initials: KR
authors.lastname: Duffy
authors.affiliation: Division of Immunology, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, the Netherlands.
authors.forename: Lianne
authors.initials: L
authors.lastname: Kok
authors.affiliation: Theoretical Biology and Bioinformatics, Utrecht University, Padualaan 8, 3584 CH Utrecht, the Netherlands.
authors.forename: Rob J
authors.initials: RJ
authors.lastname: de Boer
authors.affiliation: Division of Immunology, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, the Netherlands. Electronic address: t.schumacher@nki.nl.
authors.forename: Ton N
authors.initials: TN
authors.lastname: Schumacher
mesh_terms: D000818:Animals; D019070:Cell Lineage; D004912:Erythrocytes / Q000166:cytology; D006410:Hematopoiesis; D008214:Lymphocytes / Q000166:cytology; D051379:Mice; D008810:Mice, Inbred C57BL; D023461:Myeloid Progenitor Cells / Q000166:cytology*