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Blood, 1 April 2005, Vol. 105, No. 7, pp. 2724-2732. Prepublished online as a Blood First Edition Paper on December 14, 2004; DOI 10.1182/blood-2004-08-3037. This Article Full Text (PDF) All Versions of this Article: 2004-08-3037v1 105/7/2724    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Gothert, J. R Articles by Begley, C G Search for Related Content PubMed PubMed Citation Articles by Gothert, J. R Articles by Begley, C G Related Collections Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted August 5, 2004 Accepted December 1, 2004 In vivo fate tracing studies using the SCL stem cell enhancer: embryonic hematopoietic stem cells significantly contribute to adult hematopoiesis Joachim R Gothert*, Sonja E Gustin, Mark A Hall, Anthony R Green, Berthold Gottgens, David J Izon, and C G Begley Division of Cancer Biology, Telethon Institute for Child Health Research, Centre for Child Health Research, University of Western Australia, West Perth, WA, Australia Rotary Bone Marrow Research Laboratory, Royal Melbourne Hospital, Parkville, VIC, Australia Department of Hematology, Cambridge Institute for Medical Research, University of Cambridge, Cambridge, United Kingdom * Corresponding author; email: joachim.goethert{at}uni-essen.de. Evidence for the lineage relationship between embryonic and adult hematopoietic stem cells (HSCs) in the mouse is primarily indirect. In order to study this relationship in a direct manner we expressed the tamoxifen-inducible Cre-ERT-recombinase under the control of the SCL-stem-cell-enhancer in transgenic mice (HSC-SCL-Cre-ERT). To determine functionality, HSC-SCL-Cre-ERT transgenics were bred with Cre-reporter-mice. Flow-cytometric and transplantation studies revealed tamoxifen-dependent recombination occurring in more than 90% of adult long-term HSCs, whereas the targeted proportion within mature progenitor populations was significantly lower. Moreover, the transgene was able to irreversibly tag embryonic HSCs on days 10 and 11 of gestation. These cells contributed to bone marrow hematopoiesis five months later. In order to investigate whether the de novo HSC-generation is completed during embryogenesis, HSC-SCL-Cre-ERT marked fetal liver cells were transplanted into adult recipients. Strikingly, the proportion of marked cells within the transplanted and the in vivo-remaining HSC-compartment was not different, implying that no further HSC-generation occurred during late fetal and neonatal stages of development. These data demonstrate for the first time the direct lineage relationship between mid-gestation embryonic and adult HSCs in the mouse. Additionally, the HSC-SCL-Cre-ERT mice will provide a valuable tool to achieve temporally controlled genetic manipulation of HSCs. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Creative stem cell assays Mervin C. Yoder Blood 2005 105: 2622. [Full Text] [PDF] This article has been cited by other articles: S. L. Siggins, N.-Y N. Nguyen, M. P. McCormack, S. Vasudevan, R. Villani, S. M. 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