Growth factor independent 1 (Gfi1) is a transcriptional repressor originally 
identified as a gene activated in T-cell leukemias induced by 
Moloney-murine-leukemia virus infection. Notch1 is a transmembrane receptor that 
is frequently mutated in human T-cell acute lymphoblastic leukemia (T-ALL). Gfi1 
is an important factor in the initiation and maintenance of lymphoid leukemias 
and its deficiency significantly impedes Notch dependent initiation of T-ALL in 
animal models. Here, we show that immature hematopoietic cells require Gfi1 to 
competently integrate Notch-activated signaling. Notch1 activation coupled with 
Gfi1 deficiency early in T-lineage specification leads to a dramatic loss of 
T-cells, whereas activation in later stages leaves development unaffected. In 
Gfi1 deficient multipotent precursors, Notch activation induces lethality and is 
cell autonomous. Further, without Gfi1, multipotent progenitors do not maintain 
Notch1-activated global expression profiles typical for T-lineage precursors. In 
agreement with this, we find that both lymphoid-primed multipotent progenitors 
(LMPP) and early T lineage progenitors (ETP) do not properly form or function in 
Gfi1(-/-) mice. These defects correlate with an inability of Gfi1(-/-) 
progenitors to activate lymphoid genes, including IL7R, Rag1, Flt3 and Notch1. 
Our data indicate that Gfi1 is required for hematopoietic precursors to 
withstand Notch1 activation and to maintain Notch1 dependent transcriptional 
programming to determine early T-lymphoid lineage identity.