Role of YAP as a Mechanosensing Molecule in Stem Cells and Stem Cell-Derived Hematopoietic Cells

Abstract

Yes-associated protein (YAP) and WW domain-containing transcription regulator protein 1 (WWTR1, also known as TAZ) are transcriptional coactivators in the Hippo signaling pathway. Both are well-known regulators of cell proliferation and organ size control, and they have significant roles in promoting cell proliferation and differentiation. The roles of YAP and TAZ in stem cell pluripotency and differentiation have been extensively studied. However, the upstream mediators of YAP and TAZ are not well understood. Recently, a novel role of YAP in mechanosensing and mechanotransduction has been reported. The present review updates information on the regulation of YAP by mechanical cues such as extracellular matrix stiffness, fluid shear stress, and actin cytoskeleton tension in stem cell behaviors and differentiation. The review explores mesenchymal stem cell fate decisions, pluripotent stem cells (PSCs), self-renewal, pluripotency, and differentiation to blood products. Understanding how cells sense their microenvironment or niche and mimic those microenvironments in vitro could improve the efficiency of producing stem cell products and the efficacy of the products.

Bionic Functional Surgical Suture with Hierarchical Micro–Nano Dimensions for Rotator Cuff Repair: Inducing Process‐Matching Mechanobiological and Biological Responses Adapted to the Regeneration

“…[ 62 ] YAP is a core transcriptional coactivator in the Hippo signaling pathway, a critical mechanotransduction protein that significantly promotes cell proliferation and differentiation. [ 63 ] Cell behaviors could be affected by mechanobiological signals like the stress stimulation of the repair tissue, the ECM's stiffness, the fluid's shear stress, and the tension of the actin cytoskeleton. [ 63 ] Therefore, we detected the YAP expression for mechanobiological response in vivo at the cuff tendon and tendon–bone interface by immunofluorescent stainings.…”

“…[ 63 ] Cell behaviors could be affected by mechanobiological signals like the stress stimulation of the repair tissue, the ECM's stiffness, the fluid's shear stress, and the tension of the actin cytoskeleton. [ 63 ] Therefore, we detected the YAP expression for mechanobiological response in vivo at the cuff tendon and tendon–bone interface by immunofluorescent stainings. At the cuff tendon, the YAP started to be detectable in the TC‐nySS (20.22 ± 3.26) or nySS (22.09 ± 1.80) at 2 weeks (Figure 3d1), with a significantly higher intensity than the Con group (12.07 ± 1.28) (Figure 3d3).…”

Improving hematopoietic differentiation from human induced pluripotent stem cells by the modulation of Hippo signaling with a diarylheptanoid derivative

“…Several studies have highlighted the impact of YAP/TAZ on human hematopoiesis, particularly the dispensable YAP in the high formation of mesodermal cells toward HSPCs from hiPSCs. However, they are essential in producing lymphocytes, megakaryocytes, and erythrocytes [ 56 , 57 ]. Our data from ASPP 049-treated CD34 + CD45 + HSPCs show that the most significant DEGs related to the Hippo signaling pathway_1 include TEAD1, TEAD3, and WWTR1 (TAZ).…”

Working a second job: Cell adhesion proteins that moonlight in the nucleus

“…The composition of the focal adhesion (FA) complex, including FA proteins Integrins, Talin and Vinculin are altered in response to mechanical cues, and modify the actin/myosin cytoskeleton as well as trigger signaling cascades to induce gene expression changes. Some examples are the Rho ( Berrier et al, 2002 ) and ROCK ( Zhou et al, 2013 ) pathways, as well as activation of the YAP/TAZ transcription factors ( Totaro et al, 2018 ; Damkham et al, 2022 ). Cells can also upregulate or downregulate enzymatic activity ( Haage and Schneider, 2014 ) based on substrate stiffness.…”