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Publication : Genome-wide lineage-specific transcriptional networks underscore Ikaros-dependent lymphoid priming in hematopoietic stem cells.

First Author  Ng SY Year  2009
Journal  Immunity Volume  30
Issue  4 Pages  493-507
PubMed ID  19345118 Mgi Jnum  J:147975
Mgi Id  MGI:3843111 Doi  10.1016/j.immuni.2009.01.014
Citation  Ng SY, et al. (2009) Genome-wide lineage-specific transcriptional networks underscore Ikaros-dependent lymphoid priming in hematopoietic stem cells. Immunity 30(4):493-507
abstractText  The mechanisms regulating lineage potential during early hematopoiesis were investigated. First, a cascade of lineage-affiliated gene expression signatures, primed in hematopoietic stem cells (HSCs) and differentially propagated in lineage-restricted progenitors, was identified. Lymphoid transcripts were primed as early as the HSC, together with myeloid and erythroid transcripts. Although this multilineage priming was resolved upon subsequent lineage restrictions, an unexpected cosegregation of lymphoid and myeloid gene expression and potential past a nominal myeloid restriction point was identified. Finally, we demonstrated that whereas the zinc finger DNA-binding factor Ikaros was required for induction of lymphoid lineage priming in the HSC, it was also necessary for repression of genetic programs compatible with self-renewal and multipotency downstream of the HSC. Taken together, our studies provide new insight into the priming and restriction of lineage potentials during early hematopoiesis and identify Ikaros as a key bivalent regulator of this process.
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