| Abstract
| - TCRgene rearrangement is strictly regulated during mouse ontogeny.The V-(D)-J junctions of α β and α TCR transcripts expressed in the adult thymus are more highly diverse than those in the fetal thymus. We prevlously showed that adult hematopoletic stem cells (HSC) have a higher capacity to insert N nucleotides into Vγ4 TCR transcripts than fetal HSC and that the level of N nucleotldle insertion is determined, at least in part, at the level of HSC. To analyze this developmental change of HSC at the single cell level, we We Investigated N nucleotlde inserions in three TCR transcripts (Vγ4,Vγ 2 and Vβ8) derived from limiting numbers of fetal liver HSC by fetal thymic organ organ culture. Eight day-14 fetal liver HSC clones showed varlous levels of N nucleotlde insertlons in Vγ4 transcripts (0-78%).On the other hand, the level of N insertions was similarly regulated in Vγ4,Vγ2 andVβ8 TCR transcripts in a clone-soecufuc Way. These results suggested that the level of N Insertion is Programmed at the level of single HSC and that fetal liver contains a heterogeneous population of HSC in terms of N insertion capacity. After 3Weeks culture with a stromal and cell line, fetal HSC showed higher levels of N insertion capacity than before culture. This result and the presence of HSC With Intermediate N Insertion capacity support the hypothesls that the developmental potential of individual HSC gradually changes from fetal to adult type in one stem cell lineage.
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