The role of YAP transcription coactivator in regulating stem cell self-renewal and differentiation.

By Ian Y. Lian, Joungmok Kim, H. Okazawa, Jiagang J. Zhao, Bin Zhao, Jindan Yu, Arul M. Chinnaiyan, Mason A. Israel, L. Goldstein, Ramzey Abujarour and 2 more. Genes & Development, 2010

755 citations recorded by the source corpus.

Yes-associated protein (YAP) is a potent transcription coactivator acting via binding to the TEAD transcription factor, and plays a critical role in organ size regulation. YAP is phosphorylated and inhibited by the Lats kinase, a key component of the Hippo tumor suppressor pathway. Elevated YAP protein levels and gene amplification have been implicated in human cancer. In this study, we report that YAP is inactivated during embryonic stem (ES) cell differentiation, as indicated by decreased protein levels and increased phosphorylation. Consistently, YAP is elevated during induced pluripotent stem (iPS) cell reprogramming. YAP knockdown leads to a loss of ES cell pluripotency, while ectopic expression of YAP prevents ES cell differentiation in vitro and maintains stem cell phenotypes even under differentiation conditions. Moreover, YAP binds directly to promoters of a large number of genes known to be important for stem cells and stimulates their expression. Our observations establish a critical role of YAP in maintaining stem cell pluripotency.

Subfields: Cell Biology, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/d6d79e7e0fa0adbe0d185716ab25dc0c2eaddece

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Cell Biology

1. K. Guan
2. S. Piccolo
3. Fa-Xing Yu
4. Bin Zhao
5. G. Halder
6. M. Cordenonsi
7. Randy L. Johnson
8. H. Park

In Molecular Biology

1. K. Guan
2. Fa-Xing Yu
3. Bin Zhao
4. S. Piccolo
5. Randy L. Johnson
6. G. Halder
7. Duojia Pan
8. M. Cordenonsi

Citations in the corpus

• The Hippo Signaling Pathway in Development and Disease (2019, background): “While embryonic stem cells (ESCs) are derived from the ICM, ESCs paradoxically show nuclear accumulation of YAP (Lian et al., 2010).”
• The Hippo pathway: regulators and regulations. (2013, background): “YAP and TAZ are required for the maintenance of mouse and human embryonic stem cell pluripotency, respectively (Varelas et al. 2008; Alarcon et al. 2009; Lian et al. 2010; Qin et al. 2012).”
• The biology of YAP/TAZ: hippo signaling and beyond. (2014, background): “These findings suggest a role for YAP/TAZ activity as inhibitor of embryonic pluripotency; in contrast, YAP/TAZ have been reported to play pro-stemness roles in mouse ES cells (121).”
• The Hippo signaling pathway in stem cell biology and cancer (2014, positive): “Thus, in ESCs, YAP/TAZ promotes stemness directly, as well as indirectly by mediating TGF-b/BMP or LIF signaling, through regulating the expression of genes responsible for maintaining pluripotency both in vivo and in vitro [86,87].”
• Hippo signaling: growth control and beyond (2011, background): “Notably, different motifs in the Crb intracellular domain are required to maintain cell polarity and to bind Ex (Chen et al., 2010; Ling et al., 2010; Robinson et al., 2010).”
• Hippo Pathway in Organ Size Control, Tissue Homeostasis, and Cancer. (2015, positive): “…that YAP, and probably TAZ and Yki, may regulate transcription via multiple mechanisms, including recruitment of general transcription factors, modification of epigenetic markers, and modulation of chromatin structure (Lian et al., 2010; Stein et al., 2015; Zanconato et al., 2015) (Figure 1).”
• The two faces of Hippo: targeting the Hippo pathway for regenerative medicine and cancer treatment (2013, positive): “Indeed, in the case of murine embryonic stem cells and induced pluripotent cells, YAP appears to be capable of doing both 199 .”
• YAP/TAZ incorporation in the β-catenin destruction complex orchestrates the Wnt response. (2014, result): “A previous report suggested a positive role of YAP for the undifferentiated state of ES cells cultured in LIF (Lian et al., 2010); yet, our data do not support this conclusion in cells cultured in fully defined 2i medium.”
• The Hippo pathway effectors TAZ and YAP in development, homeostasis and disease (2014, background): “Ectopic expression of a nuclear-localized mutant YAP promotes mouse ESC self-renewal and increases the efficiency of iPSC reprogramming (Lian et al., 2010).”