期刊
STEM CELL RESEARCH & THERAPY
卷 11, 期 1, 页码 -出版社
BMC
DOI: 10.1186/s13287-020-01800-w
关键词
Embryonic stem cells; Ddx56; Proliferation; Ribosome assembly; Oct4; Sox2 complex; Cell cycle
资金
- National Key R&D Program of China [2017YFA0102801, 2017YFC1001901]
- National Nature Science Foundation of China [31671540, 31971365]
- Natural Science Foundation of Guangdong Province [2017A030313093, 2017A030313491]
- Guangdong Basic and Applied Basic Research Foundation [2019A1515011422]
Background Embryonic stem cells (ESCs) are important source of clinical stem cells for therapy, so dissecting the functional gene regulatory network involved in their self-renewal and proliferation is an urgent task. We previously reported that Ddx56 interacts with the core transcriptional factor Oct4 by mass spectrometry analysis in ESCs. However, the exact function of Ddx56 in ESCs remains unclear. Methods We investigated the role of Ddx56 in mouse ESCs (mESCs) through both gain- and loss-of-function strategies. The effect of Ddx56 on mESCs was determined based on morphological changes, involvement in the network of pluripotency markers (Nanog, Oct4, Sox2), and altered lineage marker expression. In addition, the role of Ddx56 in mESCs was evaluated by polysome fractionation, qRT-PCR, and co-immunoprecipitation (co-IP). Finally, RNA sequencing was applied to explore potential network regulation by Ddx56 in mESCs. Result We found that Ddx56 participated in ribosome assembly, as knockout or RNAi knockdown of Ddx56 led to ribosome dysfunction and cell lethality. Surprisingly, exogenous expression of C-terminal domain truncated Ddx56 (Ddx56 Delta C-ter) did not affect ribosome assembly, but decreased mESC proliferation by downregulation of proliferation-related genes and cell cycle changing. In terms of mechanism, Ddx56 interacted with the Oct4 and Sox2 complex by binding to Sox2, whereas Ddx56 Delta C-ter showed weaker interaction with Sox2 and led to retardation of mESC proliferation. Conclusions Ddx56 maintains ESC proliferation by conventional regulation of ribosome assembly and interaction with the Oct4 and Sox2 complex.
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