Early hematopoietic lineage restrictions directed by Ikaros.
Ikaros is expressed in early hematopoietic progenitors and is required for lymphoid differentiation. In the absence of Ikaros, there is a lack of markers defining fate restriction along lympho-myeloid pathways, but it is unclear whether formation of specific progenitors or expression of their markers is affected. Here we use a reporter based on Ikaros regulatory elements to separate early progenitors in wild-type and Ikaros-null mice. We found previously undetected Ikaros-null lympho-myeloid progenitors lacking the receptor tyrosine kinase Flt3 that were capable of myeloid but not lymphoid differentiation. In contrast, lack of Ikaros in the common myeloid progenitor resulted in increased formation of erythro-megakaryocytes at the expense of myeloid progenitors. Using this approach, we identify previously unknown pivotal functions for Ikaros in distinct fate 'decisions' in the early hematopoietic hierarchy.
Yoshida
Toshimi
T
Cutaneous Biology Research Center, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts 02129, USA.
Ng
Samuel Yao-Ming
SY
Zuniga-Pflucker
Juan Carlos
JC
Georgopoulos
Katia
K
D000818:Animals; D002454:Cell Differentiation / Q000276:immunology*; D003433:Crosses, Genetic; D049452:Green Fluorescent Proteins; D006410:Hematopoiesis / Q000276:immunology*; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000276:immunology*; D051740:Ikaros Transcription Factor / Q000276:immunology*; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D008856:Microscopy, Fluorescence; D022423:Myeloid Cells / Q000166:cytology / Q000276:immunology; D013047:Specific Pathogen-Free Organisms
D049452:Green Fluorescent Proteins; D051740:Ikaros Transcription Factor