Trim33 regulates early maturation of mouse embryoid bodies in vitro

Abstract

Embryonic stem cells (ESCs) are an established model for investigating developmental processes, disease conditions, tissue regeneration and therapeutic targets. Previous studies have shown that tripartite motif-containing 33 protein (Trim33) functions as a chromatin reader during Nodal-induced mesoderm induction. Here we report that despite reduced proliferation, mouse ESCs deficient in Trim33 remained pluripotent when cultured under non-differentiating conditions. However, when induced to differentiate to embryoid bodies (EBs), the mutant cultures showed increased cell shedding and apoptosis at day 3 of differentiation. Gene set enrichment analysis (GSEA) indicated that several molecular functions associated with cell survival, transcriptional/translational activity and growth factor signaling were affected already by the second day of differentiation in Trim33-deficient EBs. Consistent with increased apoptosis, expression of Rac1, a critical factor for EB cell survival, was reduced in Trim33 mutant EBs. In addition, a set of genes involved in regulation of pluripotency was upregulated in mutant EBs. Our results suggest that Trim33 regulates early maturation of mouse embryoid bodies in vitro.

The Association between TIF1 Family Members and Cancer Stemness in Solid Tumors

“…Previously, the engagement of TRIM33 protein in the regulation of stem cell phenotype has been presented in a normal embryonic stem cell population [ 35 , 36 ]. In contrast to TRIM24 and TRIM28, TRIM33 seems to be a positive regulator of stem cell differentiation.…”

“…In contrast to the other TIF1 family members, TRIM33 has predominantly been identified as a tumor suppressor [ 29 , 30 , 31 , 32 ], although several studies imply its engagement in promoting cancer progression [ 33 , 34 ]. It was previously demonstrated that TRIM33 downregulation does not affect stem cell maintenance, but instead, it alters the cell differentiation process [ 35 , 36 ]. As for TRIM66, its role in cancer progression still remains largely unknown, although a few studies suggest that TRIM66 acts as an oncogene [ 37 , 38 , 39 ].…”

The Roles of TIF1γ in Cancer

“…Transcriptional intermediary factor 1 γ (TIF1γ), synonymous with TRIM33, RFG7, PTC7, or Ectodermin, is an E3 ubiquitin-ligase family member with a ring-box-coiled-coil region (1). It has been reported to play a role in transcription elongation (2, 3), DNA repair (4), differentiation of cells (2, 5, 6), embryonic development (6–9), mitosis (10), and dermatomyositis (11–13). As transforming growth factor-β (TGF-β) superfamily signaling plays an important role in the occurrence and development of cancer (14–16), and TIF1γ was reported to be involved in the regulation of TGF-β superfamily signaling (17, 18), recent studies on TIF1γ have focused on its role in tumorigenesis (10, 19–24).…”