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.

TGF-beta-induced Foxp3 inhibits T(H)17 cell differentiation by antagonizing RORgammat function.

Abstract: T helper cells that produce IL-17 (T(H)17 cells) promote autoimmunity in mice and have been implicated in the pathogenesis of human inflammatory diseases. At mucosal surfaces, T(H)17 cells are thought to protect the host from infection, whereas regulatory T (T(reg)) cells control immune responses and inflammation triggered by the resident microflora. Differentiation of both cell types requires transforming growth factor-beta (TGF-beta), but depends on distinct transcription factors: RORgammat (encoded by Rorc(gammat)) for T(H)17 cells and Foxp3 for T(reg) cells. How TGF-beta regulates the differentiation of T cells with opposing activities has been perplexing. Here we demonstrate that, together with pro-inflammatory cytokines, TGF-beta orchestrates T(H)17 cell differentiation in a concentration-dependent manner. At low concentrations, TGF-beta synergizes with interleukin (IL)-6 and IL-21 (refs 9-11) to promote IL-23 receptor (Il23r) expression, favouring T(H)17 cell differentiation. High concentrations of TGF-beta repress IL23r expression and favour Foxp3+ T(reg) cells. RORgammat and Foxp3 are co-expressed in naive CD4+ T cells exposed to TGF-beta and in a subset of T cells in the small intestinal lamina propria of the mouse. In vitro, TGF-beta-induced Foxp3 inhibits RORgammat function, at least in part through their interaction. Accordingly, lamina propria T cells that co-express both transcription factors produce less IL-17 (also known as IL-17a) than those that express RORgammat alone. IL-6, IL-21 and IL-23 relieve Foxp3-mediated inhibition of RORgammat, thereby promoting T(H)17 cell differentiation. Therefore, the decision of antigen-stimulated cells to differentiate into either T(H)17 or T(reg) cells depends on the cytokine-regulated balance of RORgammat and Foxp3.

Dopamine neurons derived from embryonic stem cells function in an animal model of Parkinson's disease

Abstract: Parkinson's disease is a widespread condition caused by the loss of midbrain neurons that synthesize the neurotransmitter dopamine. Cells derived from the fetal midbrain can modify the course of the disease, but they are an inadequate source of dopamine-synthesizing neurons because their ability to generate these neurons is unstable. In contrast, embryonic stem (ES) cells proliferate extensively and can generate dopamine neurons. If ES cells are to become the basis for cell therapies, we must develop methods of enriching for the cell of interest and demonstrate that these cells show functions that will assist in treating the disease. Here we show that a highly enriched population of midbrain neural stem cells can be derived from mouse ES cells. The dopamine neurons generated by these stem cells show electrophysiological and behavioural properties expected of neurons from the midbrain. Our results encourage the use of ES cells in cell-replacement therapy for Parkinson's disease.

Origin, differentiation and renewal of the four main epithelial cell types in the mouse small intestine. V. Unitarian Theory of the origin of the four epithelial cell types.

Abstract: The previous articles of this series provided presumptive evidence that the four main differentiated cell types in the epithelium of the mouse small intestine: villus columnar, mucous, entero-endocrine, and Paneth cells, originate from the same precursor, the crypt-base columnar cell. In the present work, direct evidence was obtained in support of this view. It was first found that crypt-base columnar cells phagocytose non-viable cells in their vicinity, with the result that a large phagosome appears in the cytoplasm. Such phagosomes were then used as markers to follow the evolution of crypt-base columnar cells. In normal control animals, a rare crypt-base columnar cell includes a large phagosome containing Paneth cell remnants. By six hours after injection of two μCi 3H-thymidine per g body weight, a fair number of crypt-base columnar cells include a different type of phagosome containing labeled nucleus and granulefree cytoplasm, which is attributed to phagocytosis of a labeled crypt-base columnar cell killed by beta-radiation from the incorporated 3H-thymidine. By 12 hours after 3H-thymidine injection, phagosomes have appeared in partly differentiated mid-crypt columnar cells and oligomucous cells; by 18–24 hours, in fully differentiated columnar cells and in Paneth cells; and by 30 hours, in an entero-endocrine cell. Since phagosomes are first found in crypt-base columnar cells and only later in the four differentiated cell types, it is concluded that crypt-base columnar cells transform into cells of these four types and, therefore, behave as the stem cells of the epithelium. The finding of rare epithelial cells containing two different types of secretory material (either mucous globules and entero-endocrine granules, or mucous globules and Paneth cell granules) confirms that the stem cells are multipotential. These findings support the Unitarian Theory of epithelial cell formation in the small intestine.