Perovskite-organic tandem solar cells with indium oxide interconnect.

Multijunction solar cells can overcome the fundamental efficiency limits of single-junction devices. The bandgap tunability of metal halide perovskite solar cells renders them attractive for multijunction architectures1. Combinations with silicon and copper indium gallium selenide (CIGS), as well as all-perovskite tandem cells, have been reported2-5. Meanwhile, narrow-gap non-fullerene acceptors have unlocked skyrocketing efficiencies for organic solar cells6,7. Organic and perovskite semiconductors are an attractive combination, sharing similar processing technologies. Currently, perovskite-organic tandems show subpar efficiencies and are limited by the low open-circuit voltage (Voc) of wide-gap perovskite cells8 and losses introduced by the interconnect between the subcells9,10. Here we demonstrate perovskite-organic tandem cells with an efficiency of 24.0 per cent (certified 23.1 per cent) and a high Voc of 2.15 volts. Optimized charge extraction layers afford perovskite subcells with an outstanding combination of high Voc and fill factor. The organic subcells provide a high external quantum efficiency in the near-infrared and, in contrast to paradigmatic concerns about limited photostability of non-fullerene cells11, show an outstanding operational stability if excitons are predominantly generated on the non-fullerene acceptor, which is the case in our tandems. The subcells are connected by an ultrathin (approximately 1.5 nanometres) metal-like indium oxide layer with unprecedented low optical/electrical losses. This work sets a milestone for perovskite-organic tandems, which outperform the best p-i-n perovskite single junctions12 and are on a par with perovskite-CIGS and all-perovskite multijunctions13.

Differential expression of human Polycomb group proteins in various tissues and cell types.

Polycomb group proteins are involved in the maintenance of cellular identity. As multimeric complexes they repress cell type-specific sets of target genes. One model predicts that the composition of Polycomb group complexes determines the specificity for their target genes. To study this hypothesis, we analyzed the expression of Polycomb group genes in various human tissues using Northern blotting and immunohistochemistry. We found that Polycomb group expression varies greatly among tissues and even among specific cell types within a particular tissue. Variations in mRNA expression ranged from expression of all analyzed Polycomb group genes in the heart and testis to no detectable Polycomb group expression at all in bone marrow. Furthermore, each Polycomb group gene was expressed in a different number of tissues. RING1 was expressed in practically all tissues, while HPH1 was expressed in only a few tissues. Also within one tissue the level of Polycomb group expression varied greatly. Cell type-specific Polycomb group expression patterns were observed in thyroid, pancreas, and kidney. Finally, in various developmental stages of fetal kidney, different Polycomb group expression patterns were observed. We conclude that Polycomb group expression can vary depending on the tissue, cell type, and development stage. Polycomb group complexes can only be composed of the Polycomb group proteins that are expressed. This implies that with cell type-specific Polycomb group expression patterns, cell type-specific Polycomb group complexes exist. The fact that there are cell type-specific Polycomb group targets and cell type-specific Polycomb group complexes fits well with the hypothesis that the composition of Polycomb group complexes may determine their target specificity. J. Cell. Biochem. Suppl. 36: 129-143, 2001.

The Polycomb group protein EZH2 is upregulated in proliferating, cultured human mantle cell lymphoma.

Polycomb group (PcG) proteins are involved in the stable transmittance of the repressive state of their gene targets throughout the cell cycle. Mis-expression of PcG proteins can lead to proliferative defects and tumorigenesis. There are two separate multimeric PcG protein complexes: an EED-EZH2-containing complex and a BMI1-RING1-containing complex. In the normal human follicle mantle, both PcG complexes have mutually exclusive expression patterns. BMI1-RING1 is expressed, but EZH2-EED is not. Here, we studied the expression of both complexes in six cases of mantle cell lymphoma (MCL), which is derived from the follicle mantle. MCL cells can be cultured in vitro and stimulated to proliferation. We found that resting MCL cells expressed BMI1-RING1, but not EZH2-EED, like normal mantle cells. Proliferating MCL cells, however, showed strongly enhanced expression of EZH2. Also, BMI1 and RING1 continued to be expressed in proliferating MCL. This is the first demonstration that EZH2 expression can be upregulated in fresh lymphoma cells. To test whether the enhanced EZH2 expression was causal for the increased proliferation in MCL, we overexpressed EZH2 in two different cell lines. In the B cell-derived Ramos cell line, EZH2 overexpression caused an increase in the proliferation rate. This suggests a possible causal effect between EZH2 upregulation and increased proliferation in haematopoietic cells.

C-Terminal binding protein is a transcriptional repressor that interacts with a specific class of vertebrate Polycomb proteins.

Polycomb (Pc) is part of a Pc group (PcG) protein complex that is involved in repression of gene activity during Drosophila and vertebrate development. To identify proteins that interact with vertebrate Pc homologs, we performed two-hybrid screens with Xenopus Pc (XPc) and human Pc 2 (HPC2). We find that the C-terminal binding protein (CtBP) interacts with XPc and HPC2, that CtBP and HPC2 coimmunoprecipitate, and that CtBP and HPC2 partially colocalize in large PcG domains in interphase nuclei. CtBP is a protein with unknown function that binds to a conserved 6-amino-acid motif in the C terminus of the adenovirus E1A protein. Also, the Drosophila CtBP homolog interacts, through this conserved amino acid motif, with several segmentation proteins that act as repressors. Similarly, we find that CtBP binds with HPC2 and XPc through the conserved 6-amino-acid motif. Importantly, CtBP does not interact with another vertebrate Pc homolog, M33, which lacks this amino acid motif, indicating specificity among vertebrate Pc homologs. Finally, we show that CtBP is a transcriptional repressor. The results are discussed in terms of a model that brings together PcG-mediated repression and repression systems that require corepressors such as CtBP.

Characterization of interactions between the mammalian polycomb-group proteins Enx1/EZH2 and EED suggests the existence of different mammalian polycomb-group protein complexes.

In Drosophila melanogaster, the Polycomb-group (PcG) and trithorax-group (trxG) genes have been identified as repressors and activators, respectively, of gene expression. Both groups of genes are required for the stable transmission of gene expression patterns to progeny cells throughout development. Several lines of evidence suggest a functional interaction between the PcG and trxG proteins. For example, genetic evidence indicates that the enhancer of zeste [E(z)] gene can be considered both a PcG and a trxG gene. To better understand the molecular interactions in which the E(z) protein is involved, we performed a two-hybrid screen with Enx1/EZH2, a mammalian homolog of E(z), as the target. We report the identification of the human EED protein, which interacts with Enx1/EZH2. EED is the human homolog of eed, a murine PcG gene which has extensive homology with the Drosophila PcG gene extra sex combs (esc). Enx1/EZH2 and EED coimmunoprecipitate, indicating that they also interact in vivo. However, Enx1/EZH2 and EED do not coimmunoprecipitate with other human PcG proteins, such as HPC2 and BMI1. Furthermore, unlike HPC2 and BMI1, which colocalize in nuclear domains of U-2 OS osteosarcoma cells, Enx1/EZH2 and EED do not colocalize with HPC2 or BMI1. Our findings indicate that Enx1/EZH2 and EED are members of a class of PcG proteins that is distinct from previously described human PcG proteins.

Interference with the expression of a novel human polycomb protein, hPc2, results in cellular transformation and apoptosis.

Polycomb (Pc) is involved in the stable and heritable repression of homeotic gene activity during Drosophila development. Here, we report the identification of a novel human Pc homolog, hPc2. This gene is more closely related to a Xenopus Pc homolog, XPc, than to a previously described human Pc homolog, CBX2 (hPc1). However, the hPc2 and CBX2/hPc1 proteins colocalize in interphase nuclei of human U-2 OS osteosarcoma cells, suggesting that the proteins are part of a common protein complex. To study the functions of the novel human Pc homolog, we generated a mutant protein, delta hPc2, which lacks an evolutionarily conserved C-terminal domain. This C-terminal domain is important for hPc2 function, since the delta hPc2 mutant protein which lacks the C-terminal domain is unable to repress gene activity. Expression of the delta hPc2 protein, but not of the wild-type hPc2 protein, results in cellular transformation of mammalian cell lines as judged by phenotypic changes, altered marker gene expression, and anchorage-independent growth. Specifically in delta hPc2-transformed cells, the expression of the c-myc proto-oncogene is strongly enhanced and serum deprivation results in apoptosis. In contrast, overexpression of the wild-type hPc2 protein results in decreased c-myc expression. Our data suggest that hPc2 is a repressor of proto-oncogene activity and that interference with hPc2 function can lead to derepression of proto-oncogene transcription and subsequently to cellular transformation.

RING1 is associated with the polycomb group protein complex and acts as a transcriptional repressor.

The Polycomb (Pc) protein is a component of a multimeric, chromatin-associated Polycomb group (PcG) protein complex, which is involved in stable repression of gene activity. The identities of components of the PcG protein complex are largely unknown. In a two-hybrid screen with a vertebrate Pc homolog as a target, we identify the human RING1 protein as interacting with Pc. RING1 is a protein that contains the RING finger motif, a specific zinc-binding domain, which is found in many regulatory proteins. So far, the function of the RING1 protein has remained enigmatic. Here, we show that RING1 coimmunoprecipitates with a human Pc homolog, the vertebrate PcG protein BMI1, and HPH1, a human homolog of the PcG protein Polyhomeotic (Ph). Also, RING1 colocalizes with these vertebrate PcG proteins in nuclear domains of SW480 human colorectal adenocarcinoma and Saos-2 human osteosarcoma cells. Finally, we show that RING1, like Pc, is able to repress gene activity when targeted to a reporter gene. Our findings indicate that RING1 is associated with the human PcG protein complex and that RING1, like PcG proteins, can act as a transcriptional repressor.

Identification and characterization of interactions between the vertebrate polycomb-group protein BMI1 and human homologs of polyhomeotic.

In Drosophila melanogaster, the Polycomb-group (PcG) genes have been identified as repressors of gene expression. They are part of a cellular memory system that is responsible for the stable transmission of gene activity to progeny cells. PcG proteins form a large multimeric, chromatin-associated protein complex, but the identity of its components is largely unknown. Here, we identify two human proteins, HPH1 and HPH2, that are associated with the vertebrate PcG protein BMI1. HPH1 and HPH2 coimmunoprecipitate and cofractionate with each other and with BMI1. They also colocalize with BMI1 in interphase nuclei of U-2 OS human osteosarcoma and SW480 human colorectal adenocarcinoma cells. HPH1 and HPH2 have little sequence homology with each other, except in two highly conserved domains, designated homology domains I and II. They share these homology domains I and II with the Drosophila PcG protein Polyhomeotic (Ph), and we, therefore, have named the novel proteins HPH1 and HPH2. HPH1, HPH2, and BMI1 show distinct, although overlapping expression patterns in different tissues and cell lines. Two-hybrid analysis shows that homology domain II of HPH1 interacts with both homology domains I and II of HPH2. In contrast, homology domain I of HPH1 interacts only with homology domain II of HPH2, but not with homology domain I of HPH2. Furthermore, BMI1 does not interact with the individual homology domains. Instead, both intact homology domains I and II need to be present for interactions with BMI1. These data demonstrate the involvement of homology domains I and II in protein-protein interactions and indicate that HPH1 and HPH2 are able to heterodimerize.