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

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 demonst...

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Main Authors: Simon D J Calaminus, Amelie V Guitart, Amy Sinclair, Hannah Schachtner, Steve P Watson, Tessa L Holyoake, Kamil R Kranc, Laura M Machesky
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2012-01-01
Series:PLoS ONE
Online Access:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0051361&type=printable
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author Simon D J Calaminus
Amelie V Guitart
Amy Sinclair
Hannah Schachtner
Steve P Watson
Tessa L Holyoake
Kamil R Kranc
Laura M Machesky
author_facet Simon D J Calaminus
Amelie V Guitart
Amy Sinclair
Hannah Schachtner
Steve P Watson
Tessa L Holyoake
Kamil R Kranc
Laura M Machesky
author_sort Simon D J Calaminus
collection DOAJ
description 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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spelling doaj-art-c36bdc75aa094263aeb4f2c1eb9541052025-08-20T02:05:35ZengPublic Library of Science (PLoS)PLoS ONE1932-62032012-01-01712e5136110.1371/journal.pone.0051361Lineage tracing of Pf4-Cre marks hematopoietic stem cells and their progeny.Simon D J CalaminusAmelie V GuitartAmy SinclairHannah SchachtnerSteve P WatsonTessa L HolyoakeKamil R KrancLaura M MacheskyThe 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.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0051361&type=printable
spellingShingle Simon D J Calaminus
Amelie V Guitart
Amy Sinclair
Hannah Schachtner
Steve P Watson
Tessa L Holyoake
Kamil R Kranc
Laura M Machesky
Lineage tracing of Pf4-Cre marks hematopoietic stem cells and their progeny.
PLoS ONE
title Lineage tracing of Pf4-Cre marks hematopoietic stem cells and their progeny.
title_full Lineage tracing of Pf4-Cre marks hematopoietic stem cells and their progeny.
title_fullStr Lineage tracing of Pf4-Cre marks hematopoietic stem cells and their progeny.
title_full_unstemmed Lineage tracing of Pf4-Cre marks hematopoietic stem cells and their progeny.
title_short Lineage tracing of Pf4-Cre marks hematopoietic stem cells and their progeny.
title_sort lineage tracing of pf4 cre marks hematopoietic stem cells and their progeny
url https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0051361&type=printable
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