https://repository.kulib.kyoto-u.ac.jp/dspace/bitstream/2433/159777/1/j.cell.2006.07.024.pdf

Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors.

抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1（PfPMP1）与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员，通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

疟原虫var基因转换速率变化导致抗原变异[英]／Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A

https://repository.kulib.kyoto-u.ac.jp/dspace/bitstream/2433/49782/1/Yamanaka_Cell_131_5.pdf

Induction of Pluripotent Stem Cells from Adult Human Fibroblasts by Defined Factors

Comprehensive Integration of Single-Cell Data.

Computational single-cell RNA-seq (scRNA-seq) methods have been successfully applied to experiments representing a single condition, technology, or species to discover and define cellular phenotypes. However, identifying subpopulations of cells that are present across multiple data sets remains challenging. Here, we introduce an analytical strategy for integrating scRNA-seq data sets based on common sources of variation, enabling the identification of shared populations across data sets and downstream comparative analysis. We apply this approach, implemented in our R toolkit Seurat (http://satijalab.org/seurat/), to align scRNA-seq data sets of peripheral blood mononuclear cells under resting and stimulated conditions, hematopoietic progenitors sequenced using two profiling technologies, and pancreatic cell 'atlases' generated from human and mouse islets. In each case, we learn distinct or transitional cell states jointly across data sets, while boosting statistical power through integrated analysis. Our approach facilitates general comparisons of scRNA-seq data sets, potentially deepening our understanding of how distinct cell states respond to perturbation, disease, and evolution.

/pdf/integrating-single-cell-transcriptomic-data-across-different-3dtsi5w7ob.pdf

Integrating single-cell transcriptomic data across different conditions, technologies, and species.

Follistatin, an antagonist of activin, is expressed in the Spemann organizer and displays direct neuralizing activity

Multiple cell types of the pancreas appear asynchronously during embryogenesis, which requires that pancreatic progenitor cell potential changes over time. Loss-of-function studies have shown that Notch signaling modulates the differentiation of these progenitors, but it remains unclear how and when the Notch pathway acts. We established a modular transgenic system to heritably activate mouse Notch1 in multiple types of progenitors and differentiated cells. We find that misexpression of activated Notch in Pdx1-expressing progenitor cells prevents differentiation of both exocrine and endocrine lineages. Progenitors remain trapped in an undifferentiated state even if Notch activation occurs long after the pancreas has been specified. Furthermore, endocrine differentiation is associated with escape from this activity, because Ngn3-expressing endocrine precursors are susceptible to Notch inhibition, whereas fully differentiated endocrine cells are resistant.

https://www.pnas.org/content/pnas/100/25/14920.full.pdf

Notch signaling controls multiple steps of pancreatic differentiation

Publisher Summary This chapter discusses the in vitro ribonucleic acid (RNA) synthesis with SP6 RNA polymerase. The chapter describes the use of in vitro transcription systems for the synthesis of RNAs for use as substrates and hybridization probes. The chapter discusses the advantages of the technique and several associated problems. The system of SP6 RNA polymerase is used as an example throughout the chapter, but the observations are stated to be general and can be applied to any of the phage polymerase and promoter systems, including T3 and T7. The chapter discusses the in vitro transcription with bacteriophage RNA polymerase, vectors containing bacteriophage promoters, RNA synthesis reaction, and several related concepts. The optimum conditions for in vitro transcription of deoxyribonucleic acid (DNA) cloned into plasmids containing an SP6 promoter are described in the chapter. The normal product of a transcription reaction contains a triphosphate group at the 5' end of the molecule. RNA is very stable when stored as an ethanol suspension and unlike DNA it does not seem to aggregate. As a result, very reproducible samples of RNA can be taken from an ethanol suspension providing that it is vortexed prior to setting up the reaction. The chapter reviews some of the problems most commonly encountered when using in vitro transcription systems and some potential solutions.

In vitro RNA synthesis with SP6 RNA polymerase.

Notochord signals to the endoderm are required for development of the chick dorsal pancreas. Sonic hedgehog (SHH) is normally absent from pancreatic endoderm, and we provide evidence that notochord, in contrast to its effects on adjacent neuroectoderm where SHH expression is induced, represses SHH expression in adjacent nascent pancreatic endoderm. We identify activin-βB and FGF2 as notochord factors that can repress endodermal SHH and thereby permit expression of pancreas genes including Pdx1 and insulin. Endoderm treatment with antibodies that block hedgehog activity also results in pancreatic gene expression. Prevention of SHH expression in prepancreatic dorsal endoderm by intercellular signals, like activin and FGF, may be critical for permitting early steps of chick pancreatic development.

/pdf/notochord-repression-of-endodermal-sonic-hedgehog-permits-20u0kgkzx4.pdf

Notochord repression of endodermal Sonic hedgehog permits pancreas development

Type 1 diabetes (T1D) is the result of an autoimmune destruction of pancreatic β cells. The cellular and molecular defects that cause the disease remain unknown. Pluripotent cells generated from patients with T1D would be useful for disease modeling. We show here that induced pluripotent stem (iPS) cells can be generated from patients with T1D by reprogramming their adult fibroblasts with three transcription factors (OCT4, SOX2, KLF4). T1D-specific iPS cells, termed DiPS cells, have the hallmarks of pluripotency and can be differentiated into insulin-producing cells. These results are a step toward using DiPS cells in T1D disease modeling, as well as for cell replacement therapy.

/pdf/generation-of-pluripotent-stem-cells-from-patients-with-type-4t1as51n7o.pdf

Douglas A. Melton

Papers

Follistatin, an antagonist of activin, is expressed in the Spemann organizer and displays direct neuralizing activity

Notch signaling controls multiple steps of pancreatic differentiation

In vitro RNA synthesis with SP6 RNA polymerase.

Notochord repression of endodermal Sonic hedgehog permits pancreas development

Generation of pluripotent stem cells from patients with type 1 diabetes.