Lineage tracing of Pf4-Cre marks hematopoietic stem cells and their progeny (original) (raw)

Calaminus, Simon D.J., Guitart, Amelie V., Sinclair, Amy, Schachtner, Hannah, Watson, Steve P., Holyoake, Tessa L., Kranc, Kamil R. and Machesky, Laura M. ORCID: https://orcid.org/0000-0002-7592-9856(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)

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.

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Funder and Project Information

1

The role of podosomes and lamellipodia in megakaryocyte function.

Laura Machesky

FS/09/034/27756

ICS - BEATSON INSTITUTE FOR CANCER RES.

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