analysis-retinoic-acid-induced-neural-differentiation-mouse-embryonic

Analysis of Retinoic Acid-induced Neural Differentiation of Mouse Embryonic Stem Cells in Two and Three-dimensional Embryoid Bodies

Mouse embryonic stem cells (ESCs) isolated from the inner mass of the blastocyst (typically at day E3.5), can be used as in vitro model system for ...

Sidney Kimmel Medical College, Thomas Jefferson University

Soft tissue sarcomas are rare tumors representing 1% of all malignancies and less than 10% concerning head and neck tumors. We are presenting the case of a 42-year-old patient that was admitted in our service for a giant laterocervical tumor (15/12/10 cm). We performed total excision of this tumor en bloc with the involved tegument; the resulting defect was covered with a split thick skin graft. The weight of the tumor was 500 g. Histopathological examination revealed an intermediate-grade fibrosarcoma. The postoperative evolution was good; radiotherapy was indicated.

Giant laterocervical fibrosarcom.

Spontaneous neural differentiation of embryonic stem cells is induced by Noggin-mediated inhibition of bone morphogenetic protein 4 (BMP4) signaling. RhoA is a guanosine triphosphatase (GTPase) that regulates cytoskeletal dynamics and gene expression, both of which control stem cell fate. We found that disruption of Syx, a gene encoding a RhoA-specific guanine nucleotide exchange factor, accelerated retinoic acid-induced neural differentiation in murine embryonic stem cells aggregated into embryoid bodies. Cells from Syx(+/+) and Syx(-/-) embryoid bodies had different abundances of proteins implicated in stem cell pluripotency. The differentiation-promoting proteins Noggin and RARγ (a retinoic acid receptor) were more abundant in cells of Syx(-/-) embryoid bodies, whereas the differentiation-suppressing proteins SIRT1 (a protein deacetylase) and the phosphorylated form of SMAD1 (the active form of this transcription factor) were more abundant in cells of Syx(+/+) embryoid bodies. These differences were blocked by the overexpression of constitutively active RhoA, indicating that the abundance of these proteins was maintained, at least in part, by RhoA activity. The peripheral stress fibers in cells from Syx(-/-) embryoid bodies were thinner than those in Syx(+/+) cells. Furthermore, less Noggin and fewer vesicles containing Rab3d, a GTPase that mediates Noggin trafficking, were detected in cells from Syx(-/-) embryoid bodies, which could result from increased Noggin exocytosis. These results suggested that, in addition to inhibiting Noggin transcription, RhoA activity in wild-type murine embryonic stem cells also prevented neural differentiation by limiting Noggin secretion.

Ioana Stefanescu

Department of Medicine,
Cardeza Vascular Research Center,
Department of Medicine, Cardeza Vascular Research Center

Sidney Kimmel Medical College, Thomas Jefferson University

Analysis of Retinoic Acid-induced Neural Differentiation of Mouse Embryonic Stem Cells in Two and Three-dimensional Embryoid Bodies

Ioana Stefanescu

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Sidney Kimmel Medical College, Thomas Jefferson University

Analysis of Retinoic Acid-induced Neural Differentiation of Mouse Embryonic Stem Cells in Two and Three-dimensional Embryoid Bodies

Department of Medicine,
Cardeza Vascular Research Center,
Department of Medicine, Cardeza Vascular Research Center