Human STELLAR , NANOG , and GDF3 Genes Are Expressed in Pluripotent Cells and Map to Chromosome 12p13, a Hotspot for Teratocarcinoma

Abstract

Genes required to maintain pluripotency in human embryonic stem (hES) cells are largely unknown, with the exception of OCT-4, a homolog of mouse Oct-4, which is critical for the establishment of the embryonic inner cell mass and the generation of totipotent mouse embryonic stem (mES) cell lines. In the current study, we identified two genes with expression similar to OCT-4, in that they are largely restricted to pluripotent hES cells, premeiotic germ lineage cells, and testicular germ cell tumor cells. Furthermore, we determined that upon hES cell differentiation, their expression is downregulated. The genes we identified in the current study include the human stella-related (STELLAR) gene, which encodes a highly divergent protein (with just 32.1% identity to mouse stella over the 159 amino acid sequence) that maps to human chromosome 12p13. Notably, human STELLAR is located distal to a previously uncharacterized homeobox gene, which is the human homolog of the recently identified murine gene, Nanog, and proximal to the GDF3 locus, whose transcription is restricted to germ cell tumor cells. Our characterization of STELLAR, NANOG, and GDF3 suggests that they may play a similar role in humans as in mice, in spite of their remarkable evolutionary divergence.

The lymphovascular embolus of inflammatory breast cancer exhibits a Notch 3 addiction

“…Notch 3 dependency of IBC embolus Y Xiao et al properties of self-renewal and developmental potential (Bonnet and Dick, 1997;Rachel et al, 2001;Reya et al, 2001;Kubota et al, 2003;Clark et al, 2004;Sheila et al, 2004;Laurie et al, 2005;Wicha et al, 2006). Notch signaling is an example of a highly conserved pathway that is involved in multiple fundamental processes in both embryogenesis and oncogenesis (AndroutsellisTheotokis et al, 2006;Bray, 2006;Chiba, 2006).…”

Origin of pluripotent germ cell tumours: The role of microenvironment during embryonic development

“…As such, ES cells show adaptive changes during culture which mimic changes occurring in CIS and later the derived EC cells during tumour progression. Thus, the non-random genomic aberrations seen in CIS cells may be caused by selection of cells with a proliferative advantage during tumour development and progression ( Figure 3), for example those with an over-expression of the pluripotency-related genes located on the short arm of chromosome 12 (Clark et al, 2004, Korkola et al, 2006. The simplistic hypothesis would be that only a few genes are involved, perhaps only one from each region amplified.…”

Germ cell neoplasia in situ: The precursor cell for invasive germ cell tumors of the testis

“…Molecular evidence that GCNIS is derived from a fetal gonocyte is found in shared gene expression and methylation status (Almstrup et al, 2007;Clark et al, 2004). Indeed, the gene expression profile of GCNIS and fetal germ cells differed for only 5 genes in one gene expression study (Sonne et al, 2009).…”

“…GCNIS cells that are not in the physical vicinity of tumorigenic lesions generally lack short arm of chromosome 12 gain, suggesting that it is a key transformative event. This chromosomal region harbors a 200-kb gene cluster containing bona fide stem cell-related genes NANOG, STELLA and GDF3, which are also expressed and associated with pluripotency in human ES cells, and presumably similarly promote pluripotency in GCNIS (Clark et al, 2004). In GCNIS cells associated with invasive seminoma and non-seminoma there is also a typical gain of material from chromosomes 1,5,7,8,12 and X and lack of material from 4 and 13 (Summersgill et al, 2001).…”