Time : 16:00-17:30 pm, Apr.17(Wednesday)
Venue: Room 300, SIBS Main Building, Yueyang Road 320
Host：PICB Student Group
Speaker1: Lian Deng
Title: Prioritizing adaptive variants by analyzing the deep-sequenced genomes and quantitative traits of Tibetan highlanders
Abstract: Human genetic adaptation to high altitudes (>2500 m) has been extensively studied over the last few years, but few functional genetic variants have been shown to be associated with adaptive traits, largely owing to the lack of deep-genome sequencing data available to previous studies. To fully identify and prioritize known and novel adaptive genetic variants in the Tibetan people, we complied and analyzed multiple-omics data, including 77 deep-sequenced genomes (30–60×), RNA-Seq transcriptomes of 57 term placentas, and 62 quantitative traits of 2,849 Tibetan highlanders. We built a list of putative adaptive variants, including 63 missense, 7 loss-of-function, 1,298 evolutionarily conserved variants, and 509 expression quantitative traits loci. Notably, the top signal of selection is located in TMEM247, which is a transmembrane protein coding gene and harbors one high-frequency (76.3%) missense variant, rs116983452 (c.248C>T; p.Ala83Val), in Tibetan highlanders. The rs116983452-T is derived from archaic ancestry and carried by >94% of Tibetans but is absent or in low frequencies (< 3%) in non-Tibetan populations. This Tibetan-enriched allele is strongly and positively correlated with altitude, and is significantly associated with reduced hemoglobin concentration (p = 5.78×10-5), red blood cell count (p = 5.72×10-7), and hematocrit (p = 2.57×10-6). These results were further validated in 1,160 replicate Tibetan samples collected from four different altitudes. This study provides a panel of functional variants associated with a variety of adaptive phenotypes in Tibetan highlanders, many of which have not been identified in previous studies where whole-genome deep-sequencing data were not available. These results are expected to narrow down the target sequence variations for future studies and to broaden our understanding of human adaptation to the Tibetan Plateau.
Speaker2: Luyue Wang
Title: Single-cell profiling of lineage and identity in neural differentiation of human pluripotent stem cells
Abstract: Cell therapy is an important method for neurological diseases (like Parkinson’s disease) treatment. Recent study shows that dopamine neuron derived from human embryonic stem cells (hESCs) can efficiently engrafted in animal model of Parkinson’s disease and the symptoms will be significantly relieved. The challenge of cell transplantation in adult brain is low differentiation efficiency and graft-induced dyskinesia, that limited treatment effect, so if more detailed feature of specific progenitor cells can be obtained, the curative effect may be improved. What’s more, the viral-barcoding system can provide valuable information to whether cells originate from the same ancestors. At the same time, the development and stable application of single-cell RNA sequencing technology make it possible to explore the heterogeneity of individual cell transcriptome at different developmental times and locations. This presentation will introduce a series of method and some preliminary results.