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The differentiation program of embryonic definitive hematopoietic stem cells is largely alpha4 integrin independent.

TitleThe differentiation program of embryonic definitive hematopoietic stem cells is largely alpha4 integrin independent.
Publication TypeJournal Article
Year of Publication2006
AuthorsGribi R, Hook L, Ure J, Medvinsky A
JournalBlood
Volume108
Issue2
Pagination501-9
Date Published2006 Jul 15
ISSN0006-4971
KeywordsAnimals, Cell Differentiation, Embryo, Mammalian, Hematopoiesis, Hematopoietic Stem Cells, Integrin alpha4, Mice, Mice, Knockout, Myelopoiesis, Peritoneum, Peyer's Patches, Stem Cell Transplantation
Abstract

Previous analyses of the roles of alpha4 integrins in hematopoiesis by other groups have led to conflicting evidence. alpha4 integrin mutant cells developing in [alpha4 integrin(-/-): wt] chimeric mice are not capable of completing lymphomyeloid differentiation, whereas conditional inactivation of alpha4 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 alpha4 integrin(-/-) cells into the adult microenvironment results in robust and stable long-term generation of alpha4 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 alpha4 integrin during the fetal/neonatal stages of HSC development that is essential for normal execution of the lymphomyeloid differentiation program.

DOI10.1182/blood-2005-10-4209
Alternate JournalBlood
PubMed ID16551970
Grant ListG0300058 / / Medical Research Council / United Kingdom