The current classification of cells in an organism is largely based on their anatomic and developmental origin. Cells types and tissues are traditionally classified into those that arise from the three embryonic germ layers, the ectoderm, mesoderm and endoderm, but this model does not take into account the organization of cell type-specific patterns of gene expression. Here, we present computational models for cell type and tissue specification derived from a collection of 921 RNA-sequencing samples from 272 distinct mouse cell types or tissues. In an unbiased fashion, this analysis accurately predicts the three known germ layers. Unexpectedly, this analysis also suggests that in total there are eight major domains of cell type-specification, corresponding to the neurectoderm, neural crest, surface ectoderm, endoderm, mesoderm, blood mesoderm, germ cells and the embryonic domain. Further, we identify putative genes responsible for specifying the domain and the cell type. This model has implications for understanding trans-lineage differentiation for stem cells, developmental cell biology and regenerative medicine.

Abstract Previously, linalool was found to be the most abundant component among the cocktail of volatiles released from flowers of Freesia hybrida. Linalool formation is catalysed by monoterpene synthase TPS1. However, the regulatory network developmentally modulating the expression of the TPS1 gene in Freesia hybrida remains unexplored. In this study, three regulatory genes, FhMYB21L1, FhMYB21L2, and FhMYC2, were screened from 52 candidates. Two MYB transcription factor genes were synchronously expressed with FhTPS1 and could activate its expression significantly when overexpressed, and the binding of FhMYB21L2 to the MYBCORE sites in the FhTPS1 promoter was further confirmed, indicating a direct role in activation. FhMYC2 showed an inverse expression pattern compared with FhTPS1; its expression led to a decreased binding of FhMYB21 to the FhTPS1 promoter to reduce its activation capacity when co-expressed, suggesting a role for an MYB–bHLH complex in the regulation of the FhTPS1 gene. In Arabidopsis, both MYB21 and MYC2 regulators were shown to activate the expression of sesquiterpene synthase genes, and the regulatory roles of AtMYB21 and AtMYC2 in the expression of the linalool synthase gene were also confirmed, implying conserved functions of the MYB–bHLH complex in these two evolutionarily divergent plants. Moreover, the expression ratio between MYB21 and MYC2 orthologues might be a determinant factor in floral linalool emission.

Somatic cell reprogramming by exogenous factors requires cooperation with transcriptional co-activators and co-repressors to effectively remodel the epigenetic environment. How this interplay is regulated remains poorly understood. Here, we demonstrate that NCoR/SMRT co-repressors bind to pluripotency loci to create a barrier to reprogramming with the four Yamanaka factors (OCT4, SOX2, KLF4 and c-MYC), and consequently, suppressing NCoR/SMRT significantly enhances reprogramming efficiency and kinetics. The core epigenetic subunit of the NCoR/SMRT complex, histone deacetylase 3 (HDAC3), contributes to the effects of NCoR/SMRT by inducing histone deacetylation at pluripotency loci. Among the Yamanaka factors, recruitment of NCoR/SMRT-HDAC3 to genomic loci is mostly facilitated by c-MYC. Hence, we describe how c-MYC is beneficial for the early phase of reprogramming but deleterious later. Overall, we uncover a role for NCoR/SMRT co-repressors in reprogramming and propose a dual function for c-MYC in this process.

RNA-binding proteins (RBPs), in addition to their functions in cellular homeostasis, play important roles in lineage specification and maintaining cellular identity. Despite their diverse and essential functions, which touch on nearly all aspects of RNA metabolism, the roles of RBPs in somatic cell reprogramming are poorly understood. Here we show that the DEAD-box RBP DDX5 inhibits reprogramming by repressing the expression and function of the non-canonical polycomb complex 1 (PRC1) subunit RYBP. Disrupting Ddx5 expression improves the efficiency of iPSC generation and impedes processing of miR-125b, leading to Rybp upregulation and suppression of lineage-specific genes via RYBP-dependent ubiquitination of H2AK119. Furthermore, RYBP is required for PRC1-independent recruitment of OCT4 to the promoter of Kdm2b, a histone demethylase gene that promotes reprogramming by reactivating endogenous pluripotency genes. Together, these results reveal important functions of DDX5 in regulating reprogramming and highlight the importance of a Ddx5-miR125b-Rybp axis in controlling cell fate.

In this study, the phytotoxicity of seven metal oxide nanoparticles(NPs)—titanium dioxide (nTiO2), silicon dioxide (nSiO2), cerium dioxide (nCeO2), magnetite (nFe3O4), aluminum oxide (nAl2O3), zinc oxide (nZnO) and copper oxide (nCuO)—was assessed on two agriculturally significant crop plants (maize and rice). The results showed that seed germination was not affected by any of the seven metal oxide NPs. However, at the concentration of 2000 mg·L−1, the root elongation was significantly inhibited by nCuO (95.73% for maize and 97.28% for rice), nZnO (50.45% for maize and 66.75% for rice). On the contrary, minor phytotoxicity of nAl2O3 was only observed in maize, and no obvious toxic effects were found in the other four metal oxide NPs. By further study we found that the phytotoxic effects of nZnO, nAl2O3 and nCuO (25 to 2000 mg·L−1) were concentration dependent, and were not caused by the corresponding Cu2+, Zn2+ and Al3+ ions (0.11 mg·L−1, 1.27 mg·L−1 and 0.74 mg·L−1, respectively). Furthermore, ZnO NPs (<50 nm) showed greater toxicity than ZnO microparticles(MPs)(<5 μm) to root elongation of both maize and rice. Overall, this study provided valuable information for the application of engineered NPs in agriculture and the assessment of the potential environmental risks.

Floral flavonols play specific pivotal roles in pollinator attraction, pollen germination and fertility, in addition to other functions in vegetative organs. For many plants, the process of flavonol biosynthesis in late flower development stages and in mature flower tissues is poorly understood, in contrast to early flower development stages. It is thought that this process may be regulated independently of subgroup 7 R2R3 MYB (SG7 MYB) transcription factors. In this study, two FLS genes were shown to be expressed synchronously with the flower development-specific and tissue-specific biosynthesis of flavonols in Freesia hybrida. FhFLS1 contributed to flavonol biosynthesis in early flower buds, toruses and calyxes, and was regulated by four well-known SG7 MYB proteins, designated as FhMYBFs, with at least partial regulatory redundancy. FhFLS2 accounted for flavonols in late developed flowers and in the petals, stamens and pistils, and was targeted directly by non SG7 MYB protein FhMYB21L2. In parallel, AtMYB21 and AtMYB24 also activated AtFLS1, a gene highly expressed in Arabidopsis anthers and pollen, indicating the conserved regulatory roles of MYB21 against FLS genes in these two evolutionarily divergent angiosperm plants. Our results reveal a novel regulatory and synthetic mechanism underlying flavonol biosynthesis in floral organs and tissues which may be exploited to investigate supplementary roles of flavonols in flowers.

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BackgroundHematopoiesis is a progressive process collectively controlled by an elaborate network of transcription factors (TFs). Among these TFs, GATA2 has been implicated to be critical for regulating multiple steps of hematopoiesis in mouse models. However, whether similar function of GATA2 is conserved in human hematopoiesis, especially during early embryonic development stage, is largely unknown.ResultsTo examine the role of GATA2 in human background, we generated homozygous GATA2 knockout human embryonic stem cells (GATA2−/− hESCs) and analyzed their blood differentiation potential. Our results demonstrated that GATA2−/− hESCs displayed attenuated generation of CD34+CD43+ hematopoietic progenitor cells (HPCs), due to the impairment of endothelial to hematopoietic transition (EHT). Interestingly, GATA2−/− hESCs retained the potential to generate erythroblasts and macrophages, but never granulocytes. We further identified that SPI1 downregulation was partially responsible for the defects of GATA2−/− hESCs in generation of CD34+CD43+ HPCs and granulocytes. Furthermore, we found that GATA2−/− hESCs restored the granulocyte potential in the presence of Notch signaling.ConclusionOur findings revealed the essential roles of GATA2 in EHT and granulocyte development through regulating SPI1, and uncovered a role of Notch signaling in granulocyte generation during hematopoiesis modeled by human ESCs.Electronic supplementary materialThe online version of this article (doi:10.1186/s13619-015-0018-7) contains supplementary material, which is available to authorized users.