Haploinsufficiency screen highlights two distinct groups of ribosomal protein genes essential for embryonic stem cell fate
- Author(s)
- Fortier, S; MacRae, T; Bilodeau, M; Sargeant, T; Sauvageau, G;
- Details
- Publication Year 2015-02-17,Volume 112,Issue #7,Page 2127-2132
- Journal Title
- Proceedings of the National Academy of Sciences of the United States of America
- Publication Type
- Journal Article
- Abstract
- In a functional genomics screen of mouse embryonic stem cells (ESCs) with nested hemizygous chromosomal deletions, we reveal that ribosomal protein (RP) genes are the most significant haploinsufficient determinants for embryoid body (EB) formation. Hemizygocity for three RP genes (Rps5, Rps14, or Rps28), distinguished by the proximity of their corresponding protein to the ribosome's mRNA exit site, is associated with the most profound phenotype. This EB phenotype was fully rescued by BAC or cDNA complementation but not by the reduction of p53 levels, although such reduction was effective with most other RP-deleted clones corresponding to non-mRNA exit-site proteins. RNA-sequencing studies further revealed that undifferentiated ESCs hemizygous for Rps5 showed reduced expression levels of several mesoderm-specific genes as compared with wild-type counterparts. Together, these results reveal that RP gene dosage limits the differentiation, not the self-renewal, of mouse ESCs. They also highlight two separate mechanisms underlying this process, one of which is p53 independent.
- Publisher
- National Academy of Sciences
- Research Division(s)
- Molecular Medicine
- Publisher's Version
- https://doi.org/10.1073/pnas.1418845112
- Open Access at Publisher's Site
http://www.pnas.org/content/early/2015/01/29/1418845112.abstract- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2015-02-05 03:45:50
Last Modified: 2015-05-21 02:29:47