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

TitleLineage tracing of Pf4-Cre marks hematopoietic stem cells and their progeny.
Publication TypeJournal Article
Year of Publication2012
AuthorsCalaminus SDJ, Guitart A, Guitart A, Sinclair A, Schachtner H, Watson SP, Holyoake TL, Kranc KR, Machesky LM
JournalPLoS One
Volume7
Issue12
Paginatione51361
Date Published2012
ISSN1932-6203
KeywordsAnimals, 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
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.

DOI10.1371/journal.pone.0051361
Alternate JournalPLoS ONE
PubMed ID23300543
PubMed Central IDPMC3531453
Grant List15673 / / Cancer Research UK / United Kingdom
FS/09/034/27756 / / British Heart Foundation / United Kingdom
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