Biology subjects

Guo, L.

Publications and source records attributed to Guo, L..

257 records · Page 15Linked to original sources

bioRxiv2017

Resolution of Reprogramming Transition States by Single Cell RNA-Sequencing

The Yamanaka factors convert mouse embryonic fibroblasts (MEFs) into induced pluripotent stem cells (iPSCs) through a highly heterogeneous process. Here we profile single cells undergoing an optimized 7-day reprogramming process and show that cells start reprogramming relatively in sync, but diverge into two branches around day 2. The first branch of cells expressing Cd34/Fxyd5/Psca become nonpluripotent. The second one contains cells that are first Oct4+, then Dppa5a+ and pluripotent. We show that IFN-{gamma} blocks this late transition. Our results reveal the heterogeneous nature of somatic cell reprogramming, identify Dppa5a as a marker for pluripotent and innate immunity as a potential barrier for reprogramming.\n\nOne Sentence SummarySingle cell RNA sequencing reveals a continuum of cell fates from somatic to pluripotent and Dppa5a as a marker for chimera-competent iPSCs.

cell biology↗

bioRxiv2017

Stable representation of sounds in the posterior striatum during flexible auditory decisions

The neuronal pathways that link sounds to rewarded actions remain elusive. It is unclear whether neurons in the posterior tail of the dorsal striatum (which receive direct input from the auditory system) mediate action selection, as other striatal circuits do. Here, we examined the role of posterior striatal neurons in auditory decisions in mice. We found that, in contrast to the anterior dorsal striatum, activation of the posterior striatum did not elicit systematic movement. However, activation of posterior striatal neurons during sound presentation in an auditory discrimination task biased the animals choices, and transient inactivation of these neurons largely impaired sound discrimination. Moreover, the activity of these neurons reliably encoded stimulus features, but was only minimally influenced by the animals choices. Our results suggest that posterior striatal neurons play an essential role in auditory decisions, yet these neurons provide sensory information downstream rather than motor commands during well-learned sound-driven tasks.

neuroscience↗

bioRxiv2017

Precision Medicine Screening Using Whole Genome Sequencing And Advanced Imaging To Identify Disease Risk In Adults

BACKGROUNDProgress in science and technology have created the capabilities and alternatives to symptom-driven medical care. Reducing premature mortality associated with age-related chronic diseases, such as cancer and cardiovascular disease, is an urgent priority we address using advanced screening detection.\n\nMETHODSWe enrolled active adults for early detection of risk for age-related chronic disease associated with premature mortality. Whole genome sequencing together with: global metabolomics, 3D/4D imaging using non-contrast whole body magnetic resonance imaging and echocardiography, and 2-week cardiac monitoring were employed to detect age-related chronic diseases and risk for diseases.\n\nRESULTSWe detected previously unrecognized age-related chronic diseases requiring prompt (<30 days) medical attention in 17 (8%, 1:12) of 209 study participants, including 4 participants with early stage neoplasms (2%, 1:50). Likely mechanistic genomic findings correlating with clinical data were identified in 52 participants (25%. 1:4). More than three-quarters of participants (n=164, 78%, 3:4) had evidence of age-related chronic diseases or associated risk factors.\n\nCONCLUSIONSPrecision medicine screening using genomics with other advanced clinical data among active adults identified unsuspected disease risks for age-related chronic diseases associated with premature mortality. This technology-driven phenotype screening approach has the potential to extend healthy life among active adults through improved early detection and prevention of age-related chronic diseases. Our success provides a scalable strategy to move medical practice and discovery toward risk detection and disease modification thus achieving healthier extension of life.\n\nSIGNIFICANCE STATEMENTAdvances in science and technology have enabled scientists to analyze the human genome cost-effectively and to combine genome sequencing with noninvasive imaging technologies for alternatives to symptom-driven medical care. Using whole genome sequencing and noninvasive 3D/4D imaging technologies we screened 209 adults to detect age-related chronic diseases, such as cancer and cardiovascular disease. We found unrecognized age-related chronic diseases requiring prompt (<30 days) medical attention in 1:12 study participants, likely genomic findings correlating with clinical data in 1:4 participants, and evidence of age-related chronic diseases or associated risk factors in more than 3 of 4 participants. These results demonstrate that genome sequencing with clinical imaging data can be used for screening and early detection of diseases associated with premature mortality.

genomics↗

bioRxiv2017

Molecular Mapping Of YrTZ2, A Stripe Rust Resistance Gene In Wild Emmer Accession TZ-2 And Its Comparative Analyses With Aegilops tauschii

Wheat stripe rust, caused by Puccinia striiformis f. sp. tritici (Pst), is a devastating disease that can cause severe yield losses. Identification and utilization of stripe rust resistance genes are essential for effective breeding against the disease. Wild emmer accession TZ-2, originally collected from Mount Hermon, Israel, confers near-immunity resistance against several prevailing Pst races in China. A set of 200 F6:7 recombinant inbred lines (RILs) derived from a cross between susceptible durum wheat cultivar Langdon and TZ-2 was used for stripe rust evaluation. Genetic analysis indicated that the stripe rust resistance of TZ-2 to Pst race CYR34 was controlled by a single dominant gene, temporarily designated YrTZ2. Through bulked segregant analysis (BSA) and SSR mapping, YrTZ2 was located on chromosome arm 1BS and flanked by SSR markers Xwmc230 and Xgwm413 with genetic distance of 0.8 cM (distal) and 0.3 cM (proximal), respectively. By applying wheat 90K iSelect SNP genotyping assay, 11 polymorphic loci (consist of 250 SNP markers) closely linked with YrTZ2 were identified. YrTZ2 was further delimited into a 0.8 cM genetic interval between SNP marker IWB19368 and SSR marker Xgwm413, and co-segregated with SNP marker IWB28744 (attached with 28 SNP markers). Comparative genomics analyses revealed high level of collinearity between the YrTZ2 genomic region and the orthologous region of Aegilops tauschii 1DS. The genomic region between loci IWB19368 and IWB31649 harboring YrTZ2 is orthologous to a 24.5 Mb genomic region between AT1D0112 and AT1D0150, spanning 15 contigs on chromosome 1DS. The genetic and comparative maps of YrTZ2 provide framework for map-based cloning and marker-assisted selection (MAS) of YrTZ2.

plant biology↗

bioRxiv2016

Test-retest reliability of functional connectivity networks during naturalistic fMRI paradigms

Functional connectivity analysis has become a powerful tool for probing the human brain function and its breakdown in neuropsychiatry disorders. So far, most studies adopted resting state paradigm to examine functional connectivity networks in the brain, thanks to its low demand and high tolerance that are essential for clinical studies. However, the test-retest reliability of resting state connectivity measures is moderate, potentially due to its low behavioral constraint. On the other hand, naturalistic neuroimaging paradigms, an emerging approach for cognitive neuroscience with high ecological validity, could potentially improve the reliability of functional connectivity measures. To test this hypothesis, we characterized the test-retest reliability of functional connectivity measures during a natural viewing condition, and benchmarked it against resting state connectivity measures acquired within the same functional magnetic resonance imaging (fMRI) session. We found that the reliability of connectivity and graph theoretical measures of brain networks is significantly improved during natural viewing conditions over resting state conditions, with an average increase of almost 50% across various connectivity measures. Not only sensory networks for audio-visual processing become more reliable, higher order brain networks, such as default mode and attention networks, also appear to show higher reliability during natural viewing. Our results support the use of natural viewing paradigms in estimating functional connectivity of brain networks, and have important implications for clinical application of fMRI.

neuroscience↗