STEM CELLS 2007;25:1511-1520 Disclosure of potential conflicts of interest is found at the end of this article.
Summary Stem cell-niche interactions have been studied extensively with regard to cell polarity and extracellular signaling. Less is known about the way in which signals and polarity cues integrate with intracellular structures to ensure appropriate niche organization and function. Here we report that nuclear lamins function in the cyst stem cells (CySCs) of Drosophila testis to control the interaction of CySCs with the hub. This interaction is important for regulation of CySC differentiation and organization of the niche that supports the germline stem cells (GSCs). Lamin promotes nuclear retention of phosphorylated ERK in the CySC lineage by regulating the distribution of specific nucleoporins within the nuclear pores. Lamin-regulated nuclear EGFR signaling in the CySC lineage is essential for proliferation and differentiation of the GSCs and the transient amplifying germ cells. Thus, we have uncovered a role for the nuclear lamina in integration of EGF signaling to regulate stem cell niche function.
Smads are signal transducers for the transforming growth factor- superfamily of factors. In early Xenopus embryos, the transforming growth factor- member activin induces the gene Mix.2 by stimulating the formation of a multiprotein complex, activin-responsive factor (ARF). This complex contains Smad2 or Smad3, Smad4, and a novel forkhead transcription factor, FAST-1, and binds to an enhancer (activin-responsive element; ARE) that confers activin regulation of Mix.2 transcription. Both FAST-1 and Smads can bind directly to the ARE; we have investigated 1) the role of FAST-1 and Smad DNA binding sites in ARF recognition of the ARE, 2) the contributions of FAST-1 and Smad binding to ARF binding in vitro and to ARE regulation in early Xenopus embryos, 3) the extent to which different Smads can replace Smad4 in regulation of the ARE. We find that ARF binds to ARE through both FAST-1 and Smad binding sites. FAST-1 recognition of the ARE is essential both for ARF binding in vitro and activin regulation in vivo. In contrast, Smad binding of ARE is unnecessary for ARF binding or activin regulation but does enhance the binding and regulatory activity of ARF. Also, Smad3 can partially substitute for Smad4 in the regulation of the ARE. These observations elucidate how broadly expressed signal transducers (Smads) regulate a developmentally specific transcriptional response in conjunction with a temporally restricted transcription factor, FAST-1.The TGF- 1 superfamily of signaling molecules regulates diverse events during development including meso-endoderm formation in Xenopus embryos (1, 2). TGF- factors transduce signals via type I and type II serine/threonine kinase receptors, and their biological effect is achieved in part by transcriptional regulation of target genes (3-6). Ligand induces formation of a heteromeric receptor complex and phosphorylation of the type I receptor by the type II receptor. Genetic and biochemical studies have identified Smad proteins as intracellular signal transducers of TGF- signaling (7). Smad proteins contain two conserved domains, the N-terminal MH1 domain and the Cterminal MH2 domain, separated by a divergent, proline-rich linker region. Smad2 and Smad3 are phosphorylated by cognate type I receptor in response to activin/TGF- subfamily members at a carboxyl-terminal SSXS motif in their MH2 domains. The receptor-regulated Smads bring a common signal mediator Smad4 into the nucleus, and the heteromeric complex activates target gene expression (8).In early Xenopus embryos, activin, a TGF- superfamily member, induces an early meso-endodermal response gene, Mix.2 (9). An activin-induced multiprotein complex, activinresponsive factor (ARF), binds to an enhancer (activin-responsive element; ARE) that confers activin regulation of Mix.2 transcription (10). ARF has been shown to be composed of Smad2, Smad4, and a novel forkhead DNA binding domain transcription factor, 11,12). FAST-1 is a nuclear protein containing an N-terminal forkhead DNA binding domain and a C-terminal Smad interaction d...
The aim of this study was to isolate human mesenchymal stem cells (MSCs) from the gingiva (GMSCs) and confirm their multiple differentiation potentials, including the odontogenic lineage. GMSCs, periodontal ligament stem cells (PDLSCs) and dermal stem cells (DSCs) cultures were analyzed for cell shape, cell cycle, colony-forming unit-fibroblast (CFU-F) and stem cell markers. Cells were then induced for osteogenic and adipogenic differentiation and analyzed for differentiation markers (alkaline phosphatase (ALP) activity, mineralization nodule formation and Runx2, ALP, osteocalcin (OCN) and collagen I expressions for the osteogenic differentiation, and lipid vacuole formation and PPARγ-2 expression for the adipogenic differentiation). Besides, the odontogenic differentiation potential of GMSCs induced with embryonic tooth germ cell-conditioned medium (ETGC-CM) was observed. GMSCs, PDLSCs and DSCs were all stromal origin. PDLSCs showed much higher osteogenic differentiation ability but lower adipogenic differentiation potential than DSCs. GMSCs showed the medial osteogenic and adipogenic differentiation potentials between those of PDLSCs and DSCs. GMSCs were capable of expressing the odontogenic genes after ETGC-CM induction. This study provides evidence that GMSCs can be used in tissue engineering/regeneration protocols as an approachable stem cell source.
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