Translational Control in Stem Cells

Abstract

Simultaneous measurements of mRNA and protein abundance and turnover in mammalian cells, have revealed that a significant portion of the cellular proteome is controlled by mRNA translation. Recent studies have demonstrated that both embryonic and somatic stem cells are dependent on low translation rates to maintain an undifferentiated state. Conversely, differentiation requires increased protein synthesis and failure to do so prevents differentiation. Notably, the low translation in stem cell populations is independent of the cell cycle, indicating that stem cells use unique strategies to decouple these fundamental cellular processes. In this chapter, we discuss different mechanisms used by stem cells to control translation, as well as the developmental consequences of translational deregulation.

DAZL mediates a broad translational program regulating expansion and differentiation of spermatogonial progenitors

“…This breadth was not previously appreciated because prior studies identified DAZL targets in whole testes containing mixed stages of spermatogenesis 15 (Li et al, 2019;Zagore et al, 2018). At the same time, this breadth suggests a role for DAZL in the regulation of global translational levels, which balances stem cell renewal with progenitor formation in other transit-amplifying populations (Blanco et al, 2016;Signer et al, 2014; reviewed in Tahmasebi et al, 2019;Zismanov et al, 2016). Specifically, hematopoietic, hair follicle, and muscle stem cells exhibit lower rates of protein synthesis compared with the 20 progenitor cells to which they give rise (Blanco et al, 2016;Signer et al, 2014;Zismanov et al, 2016), and increased translation promotes the differentiation of stem cells into progenitors (Zismanov et al, 2016).…”

Novel insights into the emerging roles of tRNA-derived fragments in mammalian development

“…Somatic stem cells are particularly sensitive to perturbations of protein synthesis and thrive on low translational rates to maintain their undifferentiated state [58,60]. Recent studies showed that specific tRNA modifying enzymes might dynamically affect tRF production across different stem cell compartments and during development [34,41].…”

mTOR Signaling at the Crossroad between Metazoan Regeneration and Human Diseases

“…Interestingly, genes/pathways that are differentially expressed in young versus old renal progenitors include pathways with known effects on organism/stem cells aging (such as TOR) and the translational machinery [81] (Figure 5b). More generally, recent reviews have highlighted that both embryonic and adult stem cells are dependent on low rates of translation to maintain an undifferentiated state [4,82]. Pathways controlling protein synthesis such as the mTOR pathway might then have a crucial role in maintaining renal progenitors in adult cartilaginous fish.…”