Topic
Cellular differentiation
About: Cellular differentiation is a research topic. Over the lifetime, 90966 publications have been published within this topic receiving 6099252 citations. The topic is also known as: Cellular differentiation & GO:0030154.
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TL;DR: In this article, the authors reviewed the regulation of osteoblast differentiation mediated by the local factors such as bone morphogenetic proteins (BMPs) and hedgehogs and the transcription factor, core-binding factor alpha-1 (Cbfa1).
Abstract: Osteoblasts arise from common progenitors with chondrocytes, muscle and adipocytes, and various hormones and local factors regulate their differentiation. We review here regulation of osteoblast differentiation mediated by the local factors such as bone morphogenetic proteins (BMPs) and hedgehogs and the transcription factor, core-binding factor alpha-1 (Cbfa1). BMPs are the most potent regulators of osteoblast differentiation among the local factors. Sonic and Indian hedgehogs are involved in osteoblast differentiation by interacting with BMPs. Cbfa1, a member of the runt domain gene family, plays a major role in the processes of a determination of osteoblast cell lineage and maturation of osteoblasts. Cbfa1 is an essential transcription factor for osteoblast differentiation and bone formation, because Cbfa1-deficient mice completely lacked bone formation due to maturation arrest ofosteoblasts. Although the regulatory mechanism of Cbfa1 expression has not been fully clarified, BMPs are an important local factor that up-regulates Cbfa1 expression. Thus, the intimate interaction between local factors such as BMPs and hedgehogs and the transcription factor, Cbfa1, is important to osteoblast differentiation and bone formation.
726 citations
TL;DR: The recent in vitro and in vivo evidence for the role PI3K/AKT/mTOR signalling plays in the control of pluripotency and differentiation in stem cells is reviewed, with a particular focus on the molecular mechanisms underlying these functions.
Abstract: Phosphatidylinositide 3 kinases (PI3Ks) and their downstream mediators AKT and mammalian target of rapamycin (mTOR) constitute the core components of the PI3K/AKT/mTOR signalling cascade, regulating cell proliferation, survival and metabolism. Although these functions are well-defined in the context of tumorigenesis, recent studies - in particular those using pluripotent stem cells - have highlighted the importance of this pathway to development and cellular differentiation. Here, we review the recent in vitro and in vivo evidence for the role PI3K/AKT/mTOR signalling plays in the control of pluripotency and differentiation, with a particular focus on the molecular mechanisms underlying these functions.
726 citations
TL;DR: It is demonstrated that genomic methylation patterns are determined partly through differential expression of different Dnmt3a and DNmt3b isoforms, and that hypermethylation of genomic DNA by Dn MT3b is necessary for ES cells to form teratomas in nude mice.
Abstract: We have previously shown that the DNA methyltransferases Dnmt3a and Dnmt3b carry out de novo methylation of the mouse genome during early postimplantation development and of maternally imprinted genes in the oocyte. In the present study, we demonstrate that Dnmt3a and Dnmt3b are also essential for the stable inheritance, or “maintenance,” of DNA methylation patterns. Inactivation of both Dnmt3a and Dnmt3b in embryonic stem (ES) cells results in progressive loss of methylation in various repeats and single-copy genes. Interestingly, introduction of the Dnmt3a, Dnmt3a2, and Dnmt3b1 isoforms back into highly demethylated mutant ES cells restores genomic methylation patterns; these isoforms appear to have both common and distinct DNA targets, but they all fail to restore the maternal methylation imprints. In contrast, overexpression of Dnmt1 and Dnmt3b3 failed to restore DNA methylation patterns due to their inability to catalyze de novo methylation in vivo. We also show that hypermethylation of genomic DNA by Dnmt3a and Dnmt3b is necessary for ES cells to form teratomas in nude mice. These results indicate that genomic methylation patterns are determined partly through differential expression of different Dnmt3a and Dnmt3b isoforms.
725 citations
TL;DR: These findings indicate that PLT protein dosage is translated into distinct cellular responses and high levels of PLT activity promote stem cell identity and maintenance; lower levels promote mitotic activity of stem cell daughters; and further reduction in levels is required for cell differentiation.
Abstract: Factors with a graded distribution can program fields of cells in a dose-dependent manner, but no evidence has hitherto surfaced for such mechanisms in plants. In the Arabidopsis thaliana root, two PLETHORA (PLT) genes encoding AP2-domain transcription factors have been shown to maintain the activity of stem cells. Here we show that a clade of four PLT homologues is necessary for root formation. Promoter activity and protein fusions of PLT homologues display gradient distributions with maxima in the stem cell area. PLT activities are largely additive and dosage dependent. High levels of PLT activity promote stem cell identity and maintenance; lower levels promote mitotic activity of stem cell daughters; and further reduction in levels is required for cell differentiation. Our findings indicate that PLT protein dosage is translated into distinct cellular responses.
725 citations
TL;DR: Knock-in embryonic stem cells, in which GFP or lacZ was expressed from the endogenous mouse vasa homolog (Mvh), were used to visualize germ cell production during in vitro differentiation, demonstrating that ES cells can produce functional germ cells in vitro.
Abstract: Knock-in embryonic stem (ES) cells, in which GFP or lacZ was expressed from the endogenous mouse vasa homolog (Mvh), which is specifically expressed in differentiating germ cells, were used to visualize germ cell production during in vitro differentiation. The appearance of MVH-positive germ cells depended on embryoid body formation and was greatly enhanced by the inductive effects of bone morphogenic protein 4-producing cells. The ES-derived MVH-positive cells could participate in spermatogenesis when transplanted into reconstituted testicular tubules, demonstrating that ES cells can produce functional germ cells in vitro. In vitro germ cell differentiation provides a paradigm for studying the molecular basis of germ line establishment, as well as for developing new approaches to reproductive engineering.
725 citations