Crucial transitions in cancer-including tumor initiation, local expansion, metastasis, and therapeutic resistance-involve complex interactions between cells within the dynamic tumor ecosystem. Transformative single-cell genomics technologies and spatial multiplex in situ methods now provide an opportunity to interrogate this complexity at unprecedented resolution. The Human Tumor Atlas Network (HTAN), part of the National Cancer Institute (NCI) Cancer Moonshot Initiative, will establish a clinical, experimental, computational, and organizational framework to generate informative and accessible three-dimensional atlases of cancer transitions for a diverse set of tumor types. This effort complements both ongoing efforts to map healthy organs and previous largescale cancer genomics approaches focused on bulk sequencing at a single point in time. Generating single-cell, multiparametric, longitudinal atlases and integrating them with clinical outcomes should help identify novel predictive biomarkers and features as well as therapeutically relevant cell types, cell states, and cellular interactions across transitions. The resulting tumor atlases should have a profound impact on our understanding of cancer biology and have the potential to improve cancer detection, prevention, and therapeutic discovery for better precision-medicine treatments of cancer patients and those at risk for cancer.Cancer forms and progresses through a series of critical transitions-from pre-malignant to malignant states, from locally contained to metastatic disease, and from treatment-responsive to treatment-resistant tumors (Figure 1). Although specifics differ across tumor types and patients, all transitions involve complex dynamic interactions between diverse pre-malignant, malignant, and non-malignant cells (e.g., stroma cells and immune cells), often organized in specific patterns within the tumor

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Information on genetic diversity and population structure of elite wheat (Triticum aestivum L.) breeding lines promotes effective use of genetic resources. We analyzed 205 elite wheat breeding lines from major winter wheat breeding programs in the USA using 245 markers across the wheat genomes. This collection showed a high level of genetic diversity as refl ected by allele number per locus (7.2) and polymorphism information content (0.54). However, the diversity of U.S. modern wheat appeared to be lower than previously reported diversity levels in worldwide germplasm collections. As expected, this collection was highly structured according to geographic origin and market class with soft and hard wheat clearly separated from each other. Hard wheat accessions were further divided into three subpopulations. Linkage disequilibrium (LD) was primarily distributed around centromere regions. The mean genome-wide LD decay estimate was 10 cM (r 2 > 0.1), although the extent of LD was highly variable throughout the genome. Our results on genetic diversity of different gene pools and the distribution of LD facilitates the effective use of genetic resources for wheat breeding and the choice of marker density in gene mapping and markerassisted breeding. WHEAT, rice (Oryza sativa L.), and maize (Zea mays L.) are the three staple food crops in the world. As the human population increases and more maize is dedicated to a growing biofuel industry, the demand for high yields of good quality wheat grain will increase. In the past century, wheat breeders worldwide have made remarkable progress in improving disease resistance, grain yield, and end-use quality of wheat. However, continuous breeding activities may result in erosion of genetic diversity as a result of intense selection pressure, recurrent use of a few adapted elite germplasm lines as parents, and adoption of breeding schemes that do not perpetuate genetic recombination (Hoisington et al., 1999). Th e degree of genetic diversity in contemporary germplasm from breeding programs may indirectly refl ect the level of genetic progress achievable in future cultivars. Th erefore, evaluation of the genetic diversity resident in current breeding programs at the molecular level and integration of this information into cultivar development programs are essential to using genetic resources eff ectively in breeding programs (Chao et al., 2007).Genetic diversity, population structure, and LD of a population provide strategic information for association mapping and marker-assisted breeding. Th e resolution of association mapping and eff ectiveness of marker-assisted

In order to explore the possible physiological mechanism of high temperature induced sterility in rice, we examined the floret sterility and endogenous plant growth regulator contents in pollens of two hybrid rice cultivars Shanyou63 and Teyou559 that are tolerant and susceptible to high temperature, respectively. Indexes of floret sterility, pollen activity, and variation of endogenous indole-3-acetic acid (IAA), gibberellic acids (GAs), abscisic acid (ABA), free proline and soluble proteins in anthers were measured. We found that during the course of high temperature treatment, both cultivars exhibited a marked decrease in pollen activity, pollen germination and floret fertility; however, the high temperature tolerant Shanyou63 showed a much slower rate of decrease than the high temperature susceptible Teyou559. In addition, anthers of both cultivars displayed a decrease in the contents of IAA, GAs, free proline and soluble proteins but an increase in the ABA content. Yet compared to Teyou559, Shanyou63 retained significantly higher levels of free praline and GAs and a lower level of ABA, along with higher pollen vigour and pollen germination rate even after prolonged high temperature treatment. Our study suggests a possible correlation between pollen viability/floret sterility and high temperature-caused changes in IAA, GAs, ABA, free proline and soluble protein contents. The severity in these changes may reflect the variation of rice cultivars in their heat stress sensitivities for floret development.

Cellular responses to DNA damage are critical determinants of cancer development and aging-associated pathogenesis. Here we report a novel DNA damage response pathway that regulates alternative splicing of numerous gene products, including the human tumor suppressor p53, and controls DNA damage-induced cellular senescence. In brief, ionizing irradiation (IR) inhibits the activity of hSMG-1, a phosphoinositide-3-kinase-like kinase (PIKK) family member, reducing the binding of hSMG1 to a specific region of p53 precursor mRNA near exon 9 and promoting the binding of ribosomal protein L26 (RPL26) to p53 pre-mRNA. RPL26, in turn, is required for the recruitment of the Serine/Arginine-rich splicing factor, SRSF7, to p53 pre-mRNA and generation of alternatively spliced p53β RNA. Disruption of this pathway via selective knockout of p53β by CRISPR/Cas9 or down-regulation of pathway constituents significantly reduces IR-induced senescence markers and cells lacking p53β expression fail to transcriptionally repress negative regulators of cellular senescence and aging.