Lineage Tracing of Pf4-Cre Marks Hematopoietic Stem Cells and Their Progeny

被引:62
作者
Calaminus, Simon D. J. [2 ]
Guitart, Amelie [1 ]
Sinclair, Amy [1 ]
Schachtner, Hannah [2 ]
Watson, Steve P. [3 ]
Holyoake, Tessa L. [1 ]
Kranc, Kamil R. [1 ]
Machesky, Laura M. [2 ]
机构
[1] Univ Glasgow, Inst Canc Sci, Paul OGorman Leukaemia Res Ctr, Glasgow, Lanark, Scotland
[2] Univ Glasgow, Beatson Inst Canc Res, Glasgow, Lanark, Scotland
[3] Univ Birmingham, Ctr Cardiovasc Sci, Inst Biomed Res, Birmingham, W Midlands, England
基金
英国生物技术与生命科学研究理事会;
关键词
PLATELET-FUNCTION; TRANSGENIC MICE; CRE; MEGAKARYOPOIESIS; MEGAKARYOCYTE; ACTIVATION; EXPRESSION; REGULATOR; KNOCKOUTS; TISSUES;
D O I
10.1371/journal.pone.0051361
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
引用
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页数:6
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