Gene expression profiling in human fetal liver and identification of tissue- and developmental-stage-specific genes through compiled expression profiles and efficient cloning of full-length cDNAs

Fetal liver intriguingly consists of hepatic parenchymal cells and hematopo ietic stem/progenitor cells. Human fetal liver aged 22 wk of gestation (HFL 22w) corresponds to the turning point between immigration and emigration of the hematopoietic system. To gain further molecular insight into its devel opmental and functional characteristics, HFL22w was Studied by generating e xpressed Sequence tags (ESTs) and by analyzing the compiled expression prof iles of liver at different developmental stages. A total of 13,077 ESTs wer e sequenced from a 3 ' -directed cDNA library of HFL22w., and classified as follows: 5819 (44.5%) matched to known genes; 5460 (41.8%) exhibited no si gnificant homology to known genes; and the remaining 1798 (13.7%) were a ge nomic Sequences of unknown function, mitochondrial genomic sequences, or re petitive Sequences. Integration of ESTs of known human genes generated a pr ofile. including 1660 genes that could be divided into 15 gene categories a ccording to their functions. Genes related to general housekeeping, ESTs as sociated with hematopoiesis, and liver-specific genes were highly expressed . Genes for signal transduction and those associated with diseases, abnorma lities, or transcription regulation were also, noticeably active. By compar ing the expression profiles, we identified six.-ene groups that were associ ated with different developmental stages of human fetal liver, tumorigenesi s, different physiological functions of Itoh cells against the other types of hepatic cells, and fetal hematopoiesis. The gene expression profile ther efore reflected the unique functional characteristics of HFL22w remarkably. . Meanwhile, 110 full-length cDNAs of novel genes were cloned and sequenced . These novel genes might contribute to our understanding of the unique fun ctional characteristics of the human Fetal liver at 22 wk.