Human haematopoietic stem cells express Oct4 pseudogenes and lack the ability to initiate Oct4 promoter-driven gene expression

Octamer binding protein 4 (Oct4, also known as Pou5f1 and Oct3) is the transcription factor most associated with and critical for maintenance of totipotency in blastomeres and pluripotency in the inner cell mass of developing mammalian embryos [1,2]. Belonging to the POU domain family of transcription factors [2], Oct4 mediates activation or repression of target genes involved in stem cell differentiation, either as a dimeric trans-activator of gene expression or synergistically with other transcription factors such as Sox2 [3]. Until recently, Oct4 was thought to be expressed exclusively in embryonic stem (ES) cells and primordial germ cells. Several recent studies have proposed however, that Oct4 may also regulate adult stem cell multipotency, with expression detected in a variety of tissues including: bone marrow, peripheral blood and umbilical cord blood (UCB) derived cells [4-9], human progenitor-like cells from liver [10], skin epidermis [11] and hair follicles [12]. While the prospect of such genes being involved in somatic stem cell self-renewal and differentiation is appealing, caution is necessary following the discovery that some developmental genes have multiple pseudogenes [13].Mammalian genomes contain many gene-like sequences which appear similar to functional genes, but which contain defects that either prevent transcription or generate non-functional protein transcripts. A duplicated pseudogene often lacks regulatory regions [14] and may arise from gene duplication or unequal crossing-over during meiosis and can retain some intron/exon boundaries observed in the parental gene. Alternatively, processed pseudogenes or retro-transposons represent the mRNA form of the gene rather than the DNA encoded sequence and lack both intron and promoter sequences. The belief is that mRNA is converted into DNA via a reverse transcriptase event and randomly inserted back into the genome [15]. If insertion places the pseudogene under the influence of a nearby active