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

Calaminus, S. D.J., Guitart, A., Sinclair, A., Schachtner, H., Watson, S. P., Holyoake, T. L., Kranc, K. R. and Machesky, L. M. (2012) Lineage tracing of Pf4-Cre marks hematopoietic stem cells and their progeny. PLoS ONE, 7(12), e51361. (doi:10.1371/journal.pone.0051361) (PMID:23300543) (PMCID:PMC3531453)

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Publisher's URL: http://dx.doi.org/10.1371/journal.pone.0051361

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.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Machesky, Professor Laura and Sinclair, Miss Amy and Calaminus, Dr Simon and Holyoake, Professor Tessa and Guitart, Dr Amelie and Kranc, Professor Kamil
Authors: Calaminus, S. D.J., Guitart, A., Sinclair, A., Schachtner, H., Watson, S. P., Holyoake, T. L., Kranc, K. R., and Machesky, L. M.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cancer Sciences
Journal Name:PLoS ONE
Publisher:Public Library of Science
ISSN:1932-6203
ISSN (Online):1932-6203
Published Online:27 December 2012
Copyright Holders:Copyright © 2012 The Authors
First Published:First published in PloS ONE 7(12):e51361
Publisher Policy:Reproduced under a Creative Commons License
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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
533601The role of podosomes and lamellipodia in megakaryocyte function.Laura MacheskyBritish Heart Foundation (BHF)FS/09/034/27756ICS - BEATSON INSTITUTE FOR CANCER RES.