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Blood, 15 July 2006, Vol. 108, No. 2, pp. 501-509.
Prepublished online as a Blood First Edition Paper on March 21, 2006; DOI 10.1182/blood-2005-10-4209.
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HEMATOPOIESIS
The differentiation program of embryonic definitive hematopoietic stem cells is largely 4 integrin independent
Ruby Gribi,
Lilian Hook,
Janice Ure, and
Alexander Medvinsky
From the Medical Research Council (MRC) Centre Development in Stem Cell Biology, Institute for Stem Cell Research, University of Edinburgh, King's Buildings, West Mains Road, Edinburgh, United Kingdom.
Previous analyses of the roles of 4 integrins in hematopoiesis by other groups have led to conflicting evidence. 4 integrin mutant cells developing in [ 4 integrin/: wt] chimeric mice are not capable of completing lymphomyeloid differentiation, whereas conditional inactivation of 4 integrin in adult mice has only subtle effects. We show here that circumventing the fetal stage of hematopoietic stem cell (HSC) development by transplantation of embryonic 4 integrin/ cells into the adult microenvironment results in robust and stable long-term generation of 4 integrin/ lymphoid and myeloid cells, although colonization of Peyer patches and the peritoneal cavity is significantly impaired. We argue here that collectively, our data and the data from other groups suggest a specific requirement for 4 integrin during the fetal/neonatal stages of HSC development that is essential for normal execution of the lymphomyeloid differentiation program.

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