Numerous protocols have been described for producing neural retina from human pluripotent stem cells (hPSCs), many of which are based on the culture of 3D organoids. Although nearly all such methods yield at least partial segments of retinal structure with a mature appearance, variabilities exist within and between organoids that can change over a protracted time course of differentiation. Adding to this complexity are potential differences in the composition and configuration of retinal organoids when viewed across multiple differentiations and hPSC lines. In an effort to understand better the current capabilities and limitations of these cultures, we generated retinal organoids from 16 hPSC lines and monitored their appearance and structural organization over time by light microscopy, immunocytochemistry, metabolic imaging and electron microscopy. We also employed optical coherence tomography and 3D imaging techniques to assess and compare whole or broad regions of organoids to avoid selection bias. Results from this study led to the development of a practical staging system to reduce inconsistencies in retinal organoid cultures and increase rigor when utilizing them in developmental studies, disease modeling and transplantation.

The proper understanding of semiconductor devices begins at the metal-semiconductor interface. The metal/semiconductor interface itself can also be an important device, as Schottky junctions often forms when the doping in the semiconductors is low. Here, we extend the analysis of metal-silicon Schottky junctions by using graphene, an atomically thin semimetal. We show that a fundamentally new transport model is needed to describe the graphene-silicon Schottky junction. While the current-voltage behavior follows the celebrated ideal diode behavior, the details of the diode characteristics is best characterized by the Landauer transport formalism, suggesting that the injection rate from graphene ultimately determines the transport properties of this new Schottky junction.

There is a close relationship between histone acetylation and ATP-dependent chromatin remodeling that is not fully understood. We show that acetylation of histone H3 tails affects SWI/SNF (mating type switching/ sucrose non fermenting) and RSC (remodels structure of chromatin) remodeling in several distinct ways. Acetylation of the histone H3 N-terminal tail facilitated recruitment and nucleosome mobilization by the ATP-dependent chromatin remodelers SWI/SNF and RSC. Tetra-acetylated H3, but not tetra-acetylated H4 tails, increased the affinity of RSC and SWI/SNF for nucleosomes while also changing the subunits of SWI/SNF that interact with the H3 tail. The enhanced recruitment of SWI/SNF due to H3 acetylation is bromodomain dependent, but is not further enhanced by additional bromodomains found in RSC. The combined effect of H3 acetylation and transcription activators is greater than either separately which suggests they act in parallel to recruit SWI/SNF. Besides enhancing recruitment, H3 acetylation increased nucleosome mobilization and H2A/H2B displacement by RSC and SWI/SNF in a bromodomain dependent manner and to a lesser extent enhanced ATP hydrolysis independent of bromodomains. H3 and H4 acetylation did not stimulate disassembly of adjacent nucleosomes in short arrays by SWI/SNF or RSC. These data illustrate how histone acetylation modulates RSC and SWI/SNF function, and provide a mechanistic insight into their collaborative efforts to remodel chromatin.