The origin and specification of human dendritic cells (DCs) have not been investigated at clonal level. Using clonal assays combined with statistical computation to quantify the yield of granulocytes, monocytes, lymphocytes and three subsets of DCs from single human CD34+ progenitor cells, we show DC lineage specification occurs in parallel with myeloid and lymphoid lineages in HSCs, starting as a lineage bias defined by specific transcriptional programs correlated with the relative IRF8/PU.1 ratios, which is transmitted to most progeny and reinforced by FLT3L-driven IRF8 upregulation over division. We propose a model in which DC lineage specification is driven by parallel and inheritable transcriptional programs in HSCs, and reinforced over cell division by recursive interaction between transcriptional programs and extrinsic signals.
Over the last 10 years great research interest has been directed toward nanofibrous architectures produced by electrospinning bioactive plant extracts. The resulting structures possess antimicrobial, anti-inflammatory, and anti-oxidant activity, which are attractive for biomedical applications and food industry. This review describes the diverse approaches that have been developed to produce electrospun nanofibres that are able to deliver naturally-derived chemical compounds in a controlled way and to prevent their degradation. The efficacy of those composite nanofibres as wound dressings, scaffolds for tissue engineering, and active food packaging systems will be discussed.
SUMMARY
Pluripotent stem cells (PSCs) could provide a powerful system to model development of the human esophagus, whose distinct tissue organization compared to rodent esophagus suggests that developmental mechanisms may not be conserved between species. We therefore established an efficient protocol for generating esophageal epithelial progenitors (EPCs) from human PSCs. We found that inhibition of TGFß and BMP signaling is required for sequential specification of EPCs, which can be further purified using cell surface markers. These EPCs resemble their human fetal counterparts and can recapitulate normal development of esophageal stratified squamous epithelium during in vitro 3D cultures and in vivo. Importantly, combining hPSC differentiation strategies with mouse genetics elucidated a critical role for Notch signaling in the formation of this epithelium. These studies therefore not only provide an efficient approach to generate EPCs, but also offer a model system to study the regulatory mechanisms underlying development of the human esophagus.
SUMMARY
The distribution of sense and antisense strand DNA mutations on transcribed duplex DNA contributes to the development of immune and neural systems along with the progression of cancer. Because developmentally matured B cells undergo biologically programmed strand-specific DNA mutagenesis at focal DNA/RNA hybrid structures, they make a convenient system to investigate strand-specific mutagenesis mechanisms. We demonstrate that the sense and antisense strand DNA mutagenesis at the immunoglobulin heavy chain locus and some other regions of the B cell genome depends upon localized RNA processing protein complex formation in the nucleus. Both the physical proximity and coupled activities of RNA helicase Mtr4 (and Senataxin) with the noncoding RNA processing function of RNA exosome determine the strand specific distribution of DNA mutations. Our study suggests that strand-specific DNA mutagenesis-associated mechanisms will play major roles in other undiscovered aspects of organismic development.
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