Abstract
The pluripotency transcriptional network in embryonic stem cells (ESCs) is composed of distinct functional units including the core and Myc units. It is hoped that dissection of the cellular functions and interconnections of network factors will aid our understanding of ESC and cancer biology. Proteomic and genomic approaches have identified Nac1 as a member of the core pluripotency network. However, previous studies have predominantly focused on the role of Nac1 in psychomotor stimulant response and cancer pathogenesis. In this study, we report that Nac1 is a self-renewal promoting factor, but is not required for maintaining pluripotency of ESCs. Loss of function of Nac1 in ESCs results in a reduced proliferation rate and an enhanced differentiation propensity. Nac1 overexpression promotes ESC proliferation and delays ESC differentiation in the absence of leukemia inhibitory factor (LIF). Furthermore, we demonstrated that Nac1 directly binds to the c-Myc promoter and regulates c-Myc transcription. The study also revealed that the function of Nac1 in promoting ESC self-renewal appears to be partially mediated by c-Myc. These findings establish a functional link between the core and c-Myc-centered networks and provide new insights into mechanisms of stemness regulation in ESCs and cancer.
Highlights
Embryonic stem cells (ESCs) exhibit the capacity to undergo unlimited self-renewal and multilineage differentiation in vitro [1, 2]
Quantitative reverse transcriptase-PCR analysis revealed that differentiation markers associated with the three germ layers were progressively induced after embryoid body (EB) formation (Figure 1B), indicating efficient differentiation of embryonic stem cells (ESCs)
Western blot (WB) analysis confirmed that Nucleus Accumbens-1 (Nac1) was abundant in ESCs and reduced very slowly during EB formation (Figure 1D)
Summary
Embryonic stem cells (ESCs) exhibit the capacity to undergo unlimited self-renewal and multilineage differentiation in vitro [1, 2]. These properties have made ESCs a powerful model for studying embryogenesis and a great source for regenerative medicine [3, 4]. Sox and Nanog together with additional TFs form the pluripotency transcriptional network. This network is crucial in maintaining an appropriate balance between ESC self-renewal and differentiation [7, 15, 16]. In order to fully understand the mechanisms that underpin pluripotency and early development of ESCs, it is imperative that we investigate the functions and regulatory relationships associated with factors involved in these regulatory networks
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