2020
Publication by Renz et al.: Inhibition of FGF and TGF-β Pathways in hESCs Identify STOX2 as a Novel SMAD2/4 Cofactor.
Renz and colleagues examined how two pathways (the transforming growth factor- (TGF-beta) and the fibroblast growth factor (FGF)) cooperate in the maintenance and cell fate specification of human embryonic stem cells. They discovered STOX2 as a new primary target of the TGF-beta signaling pathway, suggesting that STOX2 acts as a novel TGF-beta signaling co-factor. Their work will contribute understanding how signaling by the TGF-beta is mediated.
Publication by Ngondo et al.: Fast in vitro procedure to identify extraembryonic differentiation defect of mouse embryonic stem cells.
Mouse embryonic stem cells (mESCs) are a powerful model to study early mouse development. These blastocyst-derived cells can maintain pluripotency and differentiate into the three embryonic germ layers and an extraembryonic layer, the extraembryonic endoderm (ExEn). Here, we present a fast procedure to identify a differentiation defect of mESCs toward ExEn in vitro through the molecular and cellular characterization of embryoid bodies, followed by direct differentiation of mESCs into ExEn.
Publication by Boontanrart et al.: ATF4 regulates MYB to increase γ-globin in response to loss of β-globin.
Cellular stress prompts differentiating erythroid precursors to express high levels of fetal γ-globin. We discovered that decreased adult β-globin is sufficient to induce robust re-expression of γ-globin with ATF4 being a causal regulator of this response. The reduction of ATF4 upon β-globin ko decreases the levels of MYB and BCL11A. Our findings provide mechanistic insight to the phenomenon of stress-induced globin compensation and could inform strategies to treat hemoglobinopathies.
Publication by Muri et al.: The thioredoxin-1 inhibitor Txnip retrains effector T-cell and germinal center B-cell expansion.
Thioredoxin-1 (Trx1) is a vital component for cellular redox homeostasis. Trx-interacting protein (Txnip) binds to reduced Trx1 and inhibits its activity. However, the role of Txnip in adaptive immunity is unknown. Here, we show that absence of Txnip increased proliferation of T cells and germinal center B cell responses but did not affect their development and homeostasis. Thus, this study further uncovers positive and negative control of lymphocyte proliferation by the Trx1 system.
Publication by Shin et al.: Controled cycling and quiescence enables efficient HDR in engraftment-enriched adult hematopoietic stem and progenitor cells.
In stem cells it is easier to break a gene with CRISPR genome editing than to fix it. The Corn lab and collaborators figure out why this is and how to fix it. The problem lies in a tension between quiescence and division. The authors found a way to make stem cells divide during editing and then go back into quiescence. Mutated genes can thus be repaired while keeping stemness. The approach could lead to cures for disorders such as sickle cell disease.