Abstract
Pluripotent embryonic stem cells (ESCs) are derived from early embryos and can differentiate into any type of cells in living organisms. Induced pluripotent stem cells (iPSCs) resemble ESCs, both of which serve as excellent sources to study early embryonic development and realize cell replacement therapies for age-related degenerative diseases and other cell dysfunction-related illnesses. To achieve these valuable applications, comprehensively understanding of the mechanisms underlying pluripotency maintenance and acquisition is critical. Ubiquitination modifies proteins with Ubiquitin (Ub) at the post-translational level to monitor protein stability and activity. It is extensively involved in pluripotency-specific regulatory networks in ESCs and iPSCs. Ubiquitination is achieved by sequential actions of the Ub-activating enzyme E1, Ub-conjugating enzyme E2, and Ub ligase E3. Compared with E1s and E2s, E3s are most abundant, responsible for substrate selectivity and functional diversity. In this review, we focus on E3 ligases to discuss recent progresses in understanding how they regulate pluripotency and somatic cell reprogramming through ubiquitinating core ESC regulators.
Highlights
Pluripotent embryonic stem cells (ESCs) are derived from early embryos and can differentiate into any type of cells in living organisms
We summarize the progress in understanding ubiquitination-mediated regulation of pluripotency maintenance and acquisition, and mainly discuss how E3s recognize and fine-tune the expressions and activity of core pluripotency regulators so as to achieve pluripotency maintenance and reinstatement
Pluripotent ESCs and Induced pluripotent stem cells (iPSCs) exhibit unique transcriptomic, epigenomic, and proteomic signatures, which are precisely orchestrated by the interconnected regulatory network
Summary
Embryonic development starts from the totipotent zygote. At the blastocyst stage, embryonic cells are diverged into the inner cell mass (ICM) and the external mono-layer trophectoderm [11]. Embryonal carcinoma (EC) cells are the first pluripotent cell type grown in culture Their application potential is limited because they are derived from 2 offirst teratomas/teratocarcinomas and usually abnormal in chromosomes [14,15,16,17,18,19,20,21,22]. ESCs faithfully capture the naïve pluripotency the and in vivo and [27] They superior differentiation capability and can consistently produce epiblast of themaintain blastocyst in the serum-free medium supplemented with two inhibitors (2i), germline chimeras with normal diploid karyotype [4,12,13,28]. Allow us tostem generate pluripotent cell therapy of degenerative and iPSCs similar differentiation capacity with ESCs, and allow us to generate otherpossess human diseases. Multiple E3s have been identified for their critical roles in monitoring the stability or activity of pluripotency regulators
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