Haploinsufficiency screen highlights two distinct groups of ribosomal protein genes essential for embryonic stem cell fate

• DOI: 10.1073/pnas.1418845112
• Publication Date: 2015-02-03T04:18:45Z
• Authors: Simon Fortier; Tara MacRae; Mélanie Bilodeau; Tobias Sargeant; Guy Sauvageau
• Keywords: Male; Ribosomal Proteins; 0301 basic medicine; 0303 health sciences; Haploinsufficiency; 6. Clean water; Cell Line; Mice; 03 medical and health sciences; Animals; Humans; Cell Lineage; Tumor Suppressor Protein p53; Embryonic Stem Cells

Significance Stem cells hold great promise in the field of regenerative medicine because of their capability both to self-renew and to differentiate. Regulation of these processes by molecular players is crucial to maintain stem cells' unique functions. We previously reported the generation of a library of embryonic stem cells (ESCs) with engineered chromosomal deletions, in an effort to identify novel genes or elements essential for ESC differentiation. We now reveal that ESCs heterozygous for ribosomal protein (RP)-coding genes show strong defects in embryoid body (EB) differentiation but not in self-renewal. We also identify p53-dependent and -independent mechanisms that mediate the defects in EB formation of RP-deleted clones. Together, our results highlight previously unidentified roles for RP genes in ESC fate regulation.