Integrative genome-wide approaches in embryonic stem cell research

Abstract

Embryonic stem (ES) cells are derived from blastocysts. They can differentiate into the three embryonic germ layers and essentially any type of somatic cells. Therefore, they hold great potentials in tissue regeneration therapy. The ethical issues associated with the use of human embryonic stem cells are resolved by the technical break-through of generating induced pluripotent stem (iPS) cells from various types of somatic cells. However, how ES and iPS cells self-renew and maintain their pluripotency is still largely unknown in spite of the great progresses that have been made in the last two decades. Integrative genome-wide approaches, such as gene expression microarray, chromatin immunoprecipitation based microarray (ChIP-chip) and chromatin immunoprecipitation followed by massive parallel sequencing (ChIP-seq) offer unprecedented opportunities to elucidate the mechanism of the pluripotency, reprogramming and DNA damage response of ES and iPS cells. This review summarized the fundamental biological questions about ES and iPS cells and reviewed the recent advances in ES and iPS cell research using genome-wide technologies. In the end, we offered our perspectives on the future of genome-wide studies on stem cells.

Rap2b, a novel p53 target, regulates p53-mediated pro-survival function

“…This approach has been previously used to identify p53 direct targets in mES cells. 4,28 A chemotherapeutic drug, adriamycin (also known as doxorubicin), was used to activate p53, because it induces DNA damage. Untreated cells were controls.…”

“…1 Upon various stresses, such as DNA damage, oxidative stress and oncogene overexpression, p53 is stabilized, binds to chromatin and activates or represses numerous downstream genes that elicit many cellular outcomes, such as cell cycle arrest, apoptosis, DNA repair, senescence and stem cell differentiation. [1][2][3][4] Cell cycle arrest and apoptosis are two of the major p53-regulated processes in response to DNA damage stress. The current view is that DNA damage initially activates a p53-mediated cell cycle arrest program, which allows cells more time to repair their damaged DNA and avoid mitotic catastrophe.…”

Distinct Regulatory Mechanisms and Functions for p53-Activated and p53-Repressed DNA Damage Response Genes in Embryonic Stem Cells

“…The mechanisms underlying p53-mediated differentiation and reprogramming regulations have not been fully appreciated. The relationship between p53-mediated differentiation/reprogramming regulation and tumorigenesis is also elusive (Zhang and Huang, 2010). Therefore, a genome-wide picture of p53 signaling in ES cells will greatly facilitate our understanding of the biological function of p53 in ES and iPS cells.…”

Genome-wide studies of the transcriptional regulation by p53

“…This mini-review will give an update of recent progress in using genome-wide approaches to study transcriptional regulation by p53. The basics of some genome-wide platforms, such as chromatin immunoprecipitation based microarray (ChIP-chip), ChIP-sequencing (ChIP-chip), gene expression microarray and RNA sequencing (RNA-seq), have recently been reviewed and will not be detailed here [6]. …”