Title

Survival responses of human embryonic stem cells to DNA damage

Student Author(s)

Tera Filion

GSBS Program

Cell Biology

UMMS Affiliation

Department of Cell Biology; Department of Cancer Biology

Date

9-18-2009

Document Type

Article

Medical Subject Headings

Embryonic Stem Cells; DNA Damage; Microtubule-Associated Proteins

Disciplines

Cancer Biology | Cell Biology | Life Sciences | Medicine and Health Sciences

Abstract

Pluripotent human embryonic stem (hES) cells require mechanisms to maintain genomic integrity in response to DNA damage that could compromise competency for lineage-commitment, development, and tissue-renewal. The mechanisms that protect the genome in rapidly proliferating hES cells are minimally understood. Human ES cells have an abbreviated cell cycle with a very brief G1 period suggesting that mechanisms mediating responsiveness to DNA damage may deviate from those in somatic cells. Here, we investigated how hES cells react to DNA damage induced by ionizing radiation (IR) and whether genomic insult evokes DNA repair pathways and/or cell death. We find that hES cells respond to DNA damage by rapidly inducing Caspase-3 and -8, phospho-H2AX foci, phosphorylation of p53 on Ser15 and p21 mRNA levels, as well as concomitant cell cycle arrest in G2 based on Ki67 staining and FACS analysis. Unlike normal somatic cells, hES cells and cancer cells robustly express the anti-apoptotic protein Survivin, consistent with the immortal growth phenotype. SiRNA depletion of Survivin diminishes hES survival post-irradiation. Thus, our findings provide insight into pathways and processes that are activated in human embryonic stem cells upon DNA insult to support development and tissue regeneration.

Rights and Permissions

Citation: J Cell Physiol. 2009 Sep;220(3):586-92. Link to article on publisher's site

Related Resources

Link to Article in PubMed

PubMed ID

19373864