Finally, overexpression of YAP1 in the mouse intestine leads to expansion of multipotent progenitors. Taken together, this provides evidence that YAP1 functions as a stem cell regulator. While the Hippo pathway and Yap1 has been extensively studied in other tissues, its function in the Soyasaponin-Be hematopoietic system remains largely unknown. Here we study the role of Hippo signaling in hematopoiesis by conditionally overexpressing YAP1 within the hematopoietic system in vivo. Thus, in sharp contrast to what has been described for many other tissue stem cells, increased YAP1 activity does not alter the function of hematopoietic stem and progenitor cells. An increasing body of work, generated during recent years, implicates Hippo signaling as a key determinant of stem cell function and organ size in a variety of tissues. This has to a large extent been demonstrated in gain-of-function models for YAP1, counteracting upstream Hippo signaling. To clarify whether Hippo signaling plays a significant role in hematopoiesis and in regulation of HSCs we have studied a mouse model for inducible expression of YAP1 within the hematopoietic system. We demonstrate here that enforced expression of neither wildtype nor constitutively active YAP1 alters hematopoiesis or HSC function in vivo. This is in sharp contrast to the effect seen on stem and progenitor cells in other organs such as the intestine, the brain and the skin, and suggests highly tissue specific functions of the Hippo pathway in regulating stem cells. Thus, while Yap1 has been implicated as a stemness gene in several tissues, its functions are clearly context dependent. The Hippo pathway is connected to a number of different upstream regulatory elements, most of which remain poorly Chloroprocaine hydrochloride defined in mammalian cells. Cell-cell interactions that control cell proliferation through contact-mediated inhibition has been attributed to Hippo signaling. However, a distinct property of the hematopoietic system, distinguishing it from solid organs, is the liquid nature of the tissue wherein the cells reside; blood and bone marrow. While contact-mediated inhibition of cell proliferation is an important mechanism for controlling tissue homeostasis and size of solid organs, this phenomenon may have a lesser impact on cells in a liquid tissue. This may explain why YAP1 causes cell proliferation and overgrowth in solid tissues but not in the hematopoietic system. Nf2 depletion in the liver causes a similar overgrowth phenotype as seen in livers of Mst1/Mst2 knockout mice or mice with ectopic expression of YAP1. By contrast, Nf2 depletion in hematopoietic cells has no cell autonomous effects on HSCs or progenitor cells, which is consistent with our observations of YAP1 overexpression in hematopoiesis. However, Nf2 deficiency has profound consequences on several non-hematopoietic components of the bone marrow microenvironment, which is manifested by dysregulation of stroma cells, endothelium and bone, leading to secondary effects on localization and function of HSCs. It is an interesting possibility that Nf2/Mer functions through Hippo signaling in this context, and it would therefore be of considerable interest to explore the role of YAP1 within the non-hematopoietic cells of the bone marrow microenvironment. Although it is clear that increased YAP1 activity does not influence HSCs during conditions of steady state and regeneration, we cannot exclude changes in the HSC compartment that would have consequences under conditions of severe hematopoietic stress. When analyzing the expression of potential target genes in YAPmut induced LSK cells we noted a down modulation of the cell cycle inhibitor p21. HSCs from mice lacking p21 show essentially normal function, but following severe hematopoietic stress by multiple serial transplantations become gradually exhausted.