title: Lineage tracing of Pf4-Cre marks hematopoietic stem cells and their progeny.
abstract: The development of a megakaryocyte lineage specific Cre deleter, using the Pf4 (CXCL4) promoter (Pf4-Cre), was a significant step forward in the specific analysis of platelet and megakaryocyte cell biology. However, in the present study we have employed a sensitive reporter-based approach to demonstrate that Pf4-Cre also recombines in a significant proportion of both fetal liver and bone marrow hematopoietic stem cells (HSCs), including the most primitive fraction containing the long-term repopulating HSCs. Consequently, we demonstrate that Pf4-Cre activity is not megakaryocyte lineage-specific but extends to other myeloid and lymphoid lineages at significant levels between 15-60%. Finally, we show for the first time that Pf4 transcripts are present in adult HSCs and primitive hematopoietic progenitor cells. These results have fundamental implications for the use of the Pf4-Cre mouse model and for our understanding of a possible role for Pf4 in the development of the hematopoietic lineage.
authors.affiliation: Beatson Institute for Cancer Research, University of Glasgow, Glasgow, United Kingdom.
authors.forename: Simon D J
authors.initials: SD
authors.lastname: Calaminus
authors.forename: Amelie V
authors.initials: AV
authors.lastname: Guitart
authors.forename: Amelie
authors.initials: A
authors.lastname: Guitart
authors.forename: Amy
authors.initials: A
authors.lastname: Sinclair
authors.forename: Hannah
authors.initials: H
authors.lastname: Schachtner
authors.forename: Steve P
authors.initials: SP
authors.lastname: Watson
authors.forename: Tessa L
authors.initials: TL
authors.lastname: Holyoake
authors.forename: Kamil R
authors.initials: KR
authors.lastname: Kranc
authors.forename: Laura M
authors.initials: LM
authors.lastname: Machesky
mesh_terms: D000818:Animals; D001792:Blood Platelets / Q000378:metabolism; D001854:Bone Marrow Cells / Q000166:cytology* / Q000378:metabolism; D019070:Cell Lineage; D002478:Cells, Cultured; D004247:DNA / Q000235:genetics; D005333:Fetus / Q000166:cytology* / Q000378:metabolism; D005434:Flow Cytometry; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000378:metabolism; D019426:Integrases / Q000378:metabolism*; D008099:Liver / Q000166:cytology* / Q000378:metabolism; D008214:Lymphocytes / Q000166:cytology / Q000378:metabolism; D008533:Megakaryocytes / Q000166:cytology* / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D022423:Myeloid Cells / Q000166:cytology / Q000378:metabolism; D010978:Platelet Factor 4 / Q000502:physiology*; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D010978:Platelet Factor 4; D004247:DNA; C045073:Cre recombinase; D019426:Integrases