Direct lineage conversion is a promising approach to generate therapeutically important cell types for disease modeling and tissue repair. However, the survival and function of lineage-reprogrammed cells in vivo over the long term has not been examined. Here, using an improved method for in vivo conversion of adult mouse pancreatic acinar cells toward beta cells, we show that induced beta cells persist for up to 13 months (the length of the experiment), form pancreatic islet-like structures and support normoglycemia in diabetic mice. Detailed molecular analyses of induced beta cells over 7 months reveal that global DNA methylation changes occur within 10 d, whereas the transcriptional network evolves over 2 months to resemble that of endogenous beta cells and remains stable thereafter. Progressive gain of beta-cell function occurs over 7 months, as measured by glucose-regulated insulin release and suppression of hyperglycemia. These studies demonstrate that lineage-reprogrammed cells persist for >1 year and undergo epigenetic, transcriptional, anatomical and functional development toward a beta-cell phenotype.
Owing to the diversity of composition and excellent transport properties, the ternary I−III−VI 2 type diamond-like chalcopyrite compounds are attractive functional semiconductors, including as thermoelectric materials. In this family, CuInTe 2 and CuGaTe 2 are well investigated and achieve maximum ZT values of ∼1.4 at 950 K and an average ZT of 0.43. However, both compounds have poor electrical conductivity at low temperature, resulting in low ZT below 450 K. In this work, we have greatly improved the thermoelectric performance in the quinary diamondoid compound (Cu 0.8 Ag 0.2 )(In 0.2 Ga 0.8 )Te 2 by understanding and controlling the effects of different constituent elements on the thermoelectric transport properties. Our combined theoretical and experimental effort indicates that Ga in the In site of the lattice decreases the carrier effective mass and improves the electrical conductivity and power factor of Cu 0.8 Ag 0.2 In 1−x Ga x Te 2 . Furthermore, Ag in the Cu site strongly suppresses the heat transport via the enhanced acoustic phonon−optical phonon coupling effects, leading to the ultralow thermal conductivity of ∼0.49 W m −1 K −1 at 850 K in Cu 0.8 Ag 0.2 In 0.2 Ga 0.8 Te 2 . Defect formation energy calculations suggest intrinsic Cu vacancies introduce defect levels that are important to the temperature-dependent hole density and electrical conductivity. Therefore, we introduced extra Cu vacancies to optimize the hole carrier density and improve the power factor of Cu 0.8 Ag 0.2 In 0.2 Ga 0.8 Te 2 . As a result, a maximum ZT of ∼1.5 at 850 K and an average ZT of 0.78 in the temperature range of 400−850 K are obtained, which is among the highest in the diamond-like compound family.
The understanding of thermoelectric properties of ternary I− III−VI 2 type (I = Cu, Ag; III = Ga, In; and VI = Te) chalcopyrites is less well developed. Although their thermal transport properties are relatively well studied, the relationship between the electronic band structure and charge transport properties of chalcopyrites has been rarely discussed. In this study, we reveal the unusual electronic band structure and the dynamic doping effect that could underpin the promising thermoelectric properties of Cu 1−x Ag x GaTe 2 compounds. Density functional theory (DFT) calculations and electronic transport measurements suggest that the Cu 1−x Ag x GaTe 2 compounds possess an unusual non-parabolic band structure, which is important for obtaining a high Seebeck coefficient. Moreover, a mid-gap impurity level was also observed in Cu 1−x Ag x GaTe 2 , which leads to a strong temperature-dependent carrier concentration and is able to regulate the carrier density at the optimized value for a wide temperature region and thus is beneficial to obtaining the high power factor and high average ZT of Cu 1−x Ag x GaTe 2 compounds. We also demonstrate a great improvement in the thermoelectric performance of Cu 1−x Ag x GaTe 2 by introducing Cu vacancies and ZnTe alloying. The Cu vacancies are effective in increasing the hole density and the electrical conductivity, while ZnTe alloying reduces the thermal conductivity. As a result, a maximum ZT of 1.43 at 850 K and a record-high average ZT of 0.81 for the Cu 0.68 Ag 0.3 GaTe 2 −0.5%ZnTe compound are achieved.
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