Person: Tan, Longzhi
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Tan
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Longzhi
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Tan, Longzhi
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Publication Rare event of histone demethylation can initiate singular gene expression of olfactory receptors(Proceedings of the National Academy of Sciences, 2013) Tan, Longzhi; Zong, Chenghang; Xie, XiaoliangIn mammals, the sense of odors relies on the peculiar expression pattern of olfactory receptors (ORs). Each single neuron chooses one, and only one, from all ∼1,400 OR genes that are present in a mouse genome. In neurobiology, a long-standing mystery is how such singularity can be achieved. We show theoretically that a simple kinetic scheme of OR activation followed by feedback can be solely responsible for the observed singularity, as long as the two timescales—slow activation by epigenetic modification and fast feedback by transcriptional regulation—are well separated. Our work provides the theoretical underpinning behind the choice of ORs, and demonstrates how the nervous system utilizes the kinetics of epigenetic changes to direct neurogenesis.Publication Modeling Recent Human Evolution in Mice by Expression of a Selected EDAR Variant(Elsevier BV, 2013) Kamberov, Yana; Wang, Sijia; Tan, Jingze; Gerbault, Pascale; Wark, Abigail; Tan, Longzhi; Yang, Yajun; Li, Shilin; Tang, Kun; Chen, Hua; Powell, Adam; Itan, Yuval; Fuller, Dorian; Lohmueller, Jason; Mao, Junhao; Schachar, Asa; Paymer, Madeline; Hostetter, Elizabeth; Byrne, Elizabeth; Burnett, Melissa; McMahon, Andrew P.; Thomas, Mark G.; Lieberman, Daniel; Jin, Li; Tabin, Clifford; Morgan, Bruce; Sabeti, PardisAn adaptive variant of the human Ectodysplasin receptor, EDARV370A, is one of the strongest candidates of recent positive selection from genome-wide scans. We have modeled EDAR370A in mice and characterized its phenotype and evolutionary origins in humans. Our computational analysis suggests the allele arose in central China approximately 30,000 years ago. Although EDAR370A has been associated with increased scalp hair thickness and changed tooth morphology in humans, its direct biological significance and potential adaptive role remain unclear. We generated a knockin mouse model and find that, as in humans, hair thickness is increased in EDAR370A mice. We identify new biological targets affected by the mutation, including mammary and eccrine glands. Building on these results, we find that EDAR370A is associated with an increased number of active eccrine glands in the Han Chinese. This interdisciplinary approach yields unique insight into the generation of adaptive variation among modern humans.Publication Olfactory sensory neurons transiently express multiple olfactory receptors during development(John Wiley and Sons Inc., 2015) Tan, Longzhi; Li, Qian; Xie, X SunneyAbstract In mammals, each olfactory sensory neuron randomly expresses one, and only one, olfactory receptor (OR)—a phenomenon called the “one‐neuron‐one‐receptor” rule. Although extensively studied, this rule was never proven for all ~1,000 OR genes in one cell at once, and little is known about its dynamics. Here, we directly tested this rule by single‐cell transcriptomic sequencing of 178 cells from the main olfactory epithelium of adult and newborn mice. To our surprise, a subset of cells expressed multiple ORs. Most of these cells were developmentally immature. Our results illustrated how the “one‐neuron‐one‐receptor” rule may have been established: At first, a single neuron temporarily expressed multiple ORs—seemingly violating the rule—and then all but one OR were eliminated. This work provided experimental evidence that epigenetic regulation in the olfactory system selects a single OR by suppressing a few transiently expressed ORs in a single cell during development.