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

Simon D J Calaminus, Amelie Guitart, Amy Sinclair, Hannah Schachtner, Steve P Watson, Tessa L Holyoake, Kamil R Kranc, Laura M Machesky

Research output: Contribution to journalArticlepeer-review

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.
Original languageEnglish
Pages (from-to)e51361
JournalPLoS ONE
Volume7
Issue number12
DOIs
Publication statusPublished - 27 Dec 2012

Keywords

  • Animals
  • Blood Platelets
  • Bone Marrow Cells
  • Cell Lineage
  • Cells, Cultured
  • DNA
  • Fetus
  • Flow Cytometry
  • Hematopoietic Stem Cells
  • Integrases
  • Liver
  • Lymphocytes
  • Megakaryocytes
  • Mice
  • Mice, Transgenic
  • Myeloid Cells
  • Platelet Factor 4
  • Real-Time Polymerase Chain Reaction

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