Lineage tracing of Pf4-Cre marks hematopoietic stem cells and their progeny

• Published in: PloS one Vol. 7; no. 12; p. e51361
• Main Authors: Calaminus, Simon D J, Guitart, Amelie V, Guitart, Amelie, Sinclair, Amy, Schachtner, Hannah, Watson, Steve P, Holyoake, Tessa L, Kranc, Kamil R, Machesky, Laura M
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 27-12-2012; Public Library of Science (PLoS)
• Subjects: Analysis; Animals; B cells; Biology; Blood platelets; Blood Platelets - metabolism; Bone marrow; Bone Marrow Cells - cytology; Bone Marrow Cells - metabolism; Cancer; Cell Lineage; Cells (biology); Cells, Cultured; DNA - genetics; Fetus - cytology; Fetus - metabolism; Fetuses; Flow Cytometry; Gene expression; Hematology; Hematopoietic stem cells; Hematopoietic Stem Cells - cytology; Hematopoietic Stem Cells - metabolism; Human health and pathology; Integrases - metabolism; Journalistic ethics; Kinases; Leukemia; Life Sciences; Liver; Liver - cytology; Liver - metabolism; Lymphocytes - cytology; Lymphocytes - metabolism; Medical research; Medicine; Megakaryocytes - cytology; Megakaryocytes - metabolism; Mice; Mice, Transgenic; Myeloid Cells - cytology; Myeloid Cells - metabolism; Platelet Factor 4 - physiology; Progeny; Real-Time Polymerase Chain Reaction; Rodents; Stem cell transplantation; Stem cells; Studies; Transgenic animals
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0051361

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.