Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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Outline of Final Research Achievements |
We established two Ebf1-deficient pro-B cell lines possessing the different potential for the T cell differentiation. Comparing their expression profiles, Lmo2 transcripts were detected in pro-B(+) cells three-fold greater than in pro-B(-) cells, and its overexpression in pro-B(-) cells was sufficient to provide the differentiation potential. These suggested that Lmo2 has critical role to keep the differentiation potential. We found Bcl11a as a downstream target of Lmo2. Bcl11a was essential for the maintenance of cell survival via the induction of Bcl2. Moreover, Lmo2 also altered the epigenetic status of Tcf7 gene, which is necessary for the full activation of the gene locus with Notch signaling. These results suggested that Lmo2 functions to regulate both Bcl11a and Tcf1 as downstream targets and contributes to the maintenance of the competence to respond to Notch signaling at early T cell progenitor stage.
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