title: Cdk2ap2 is a novel regulator for self-renewal of murine embryonic stem cells.
abstract: In this study we present data to support the role for Cdk2ap2 in regulating self-renewal of mouse embryonic stem cells (mESCs) under permissive conditions, and cell survival during differentiation of the mESCs into terminally differentiated cell types. To understand the function of Cdk2ap2 during early development, we generated mESCs with homozygous disruption of the endogenous Cdk2ap2 locus (Cdk2ap2(tr/tr)). The Cdk2ap2(tr/tr) mESCs, when grown in a complete growth medium containing leukemia inhibitory factor (LIF), showed an early differentiation phenotype characterized by flattened colonies and a distinct intercellular boundary. We also observed downregulation of Nanog and upregulation in markers of mesoderm and endoderm differentiation, including Brachyury (T), Afp, and S100a, when compared to Wt mESCs. Cdk2ap2(tr/tr) mESCs were able to form embryoid bodies (EBs); however, those EBs were unhealthy and had an increased level of apoptosis. Furthermore, Cdk2ap2(tr/tr) mESCs were unable to form teratomas in severe combined immunodeficiency (SCID) mice. Cdk2ap2 under normal conditions has a biphasic expression, suggesting regulatory roles in early-versus-late stem cell differentiation. These data begin to add to our understanding of how Cdk2ap2 may be involved in the regulation of self-renewal of stem cells during early embryogenesis.
authors.affiliation: School of Dentistry and Dental Research Institute, UCLA, Los Angeles, California 90095, USA. adeshpan@alumni.uconn.edu
authors.forename: Amit M
authors.initials: AM
authors.lastname: Deshpande
authors.forename: Omar
authors.initials: O
authors.lastname: Khalid
authors.forename: Jeffrey J
authors.initials: JJ
authors.lastname: Kim
authors.forename: Yong
authors.initials: Y
authors.lastname: Kim
authors.forename: Anne
authors.initials: A
authors.lastname: Lindgren
authors.forename: Amander T
authors.initials: AT
authors.lastname: Clark
authors.forename: David T W
authors.initials: DT
authors.lastname: Wong
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D015415:Biomarkers / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics; D019070:Cell Lineage / Q000235:genetics; D049109:Cell Proliferation; D002470:Cell Survival; D015536:Down-Regulation / Q000235:genetics; D058732:Embryoid Bodies / Q000166:cytology / Q000378:metabolism; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000378:metabolism*; D004707:Endoderm / Q000166:cytology; D016147:Genes, Tumor Suppressor; D005838:Genotype; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D053605:Leukemia Inhibitory Factor / Q000378:metabolism; D008648:Mesoderm / Q000166:cytology; D051379:Mice; D000071317:Nanog Homeobox Protein; D015513:Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D010641:Phenotype; D013724:Teratoma / Q000473:pathology; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation / Q000235:genetics
chemical_list: D015415:Biomarkers; C485718:Doc-1r protein, mouse; D018398:Homeodomain Proteins; D053605:Leukemia Inhibitory Factor; D000071317:Nanog Homeobox Protein; C475540:Nanog protein, mouse; D015513:Oncogene Proteins; D025521:Tumor Suppressor Proteins