At one end of the hierarchy are stem cells expressing most
pluripotency genes studied and few lineage specific genes; at the other end are fully committed cells that have extinguished the pluripotency program, and in between there is a continuous spectrum.
Not exact matches
Yamanaka and Takahashi began their search by
studying embryonic stem cells in the hope of identifying the
genes that underlie essential stem cell characteristics, such as
pluripotency and proliferation, a cell's ability to replicate itself.
In the
study, the researchers compared how well CRISPRi and CRISPR - Cas9 silenced a particular
gene that controls iPSC
pluripotency — the capability of iPSCs to turn into multiple cell types.
Future
studies will be aimed at determining the site - specificity for this effect, that is, why the effects are seen specifically at
pluripotency genes.
Furthermore, genome - wide
studies, combining chromatin immunoprecipitation (ChIP) and array hybridization (ChIP - on - chip), have revealed that both active and silenced
genes are directly bound in ES cells by one or more of the core
pluripotency factors Oct4, Sox2 and Nanog [17], [19], [63].
In the present
study, we again observed a continuous gradient in the expression of
pluripotency genes across the cell populations that paralleled the gradient in cell surface marker expression.
Functional
studies have highlighted the critical roles of
genes such as Oct4 (Pou5f1), Nanog and Sox2 in the maintenance of ES
pluripotency and suppression of differentiation pathways [10]--[19].
The present
study shows that such a gradient is also seen at the level of single cell analysis, but reveals that there is considerable cell - to - cell variation within this gradient in the expression of
pluripotency genes.
Oct - 4 is most consistently expressed of the
pluripotency genes that we have
studied, and it is switched off only in populations that have lost other measurable features of
pluripotency, such as stem cell surface marker expression and the capacity for self - renewal.
Recent
studies of the ES cell transcriptome and epigenome have revealed networks of co-regulated transcription factors that maintain
pluripotency and suppress the expression of
genes associated with particular differentiation lineages [2].
Thus, as anticipated from earlier
studies, heterogeneity of
pluripotency gene expression in single cells is to a degree reflected at the protein level.