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Single-cell profiling reveals Müller glia coordinate retinal intercellular communication during light/dark adaptation via thyroid hormone signaling |
Min Wei1,2,3, Yanping Sun1,2,3, Shouzhen Li1,2,3, Yunuo Chen1,2,3, Longfei Li1,2,3, Minghao Fang1,2,3, Ronghua Shi3, Dali Tong1,2,3, Jutao Chen1,2,3, Yuqian Ma1,2,3( ), Kun Qu1,2,3( ), Mei Zhang1,2,3( ), Tian Xue1,2,3,4,5( ) |
1. Division of Life Sciences and Medicine, Department of Ophthalmology, The First Affiliated Hospital of USTC, University of Science and Technology of China, Hefei 230026, China 2. Hefei National Research Center for Physical Sciences at the Microscale, Neurodegenerative Disorder Research Center, CAS Key Laboratory of Brain Function and Disease, University of Science and Technology of China, Hefei 230026, China 3. Division of Life Sciences and Medicine, School of Life Sciences, University of Science and Technology of China, Hefei 230026, China 4. Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai 200031, China 5. Institute for Stem Cell and Regeneration, Chinese Academy of Sciences, Beijing 100864, China |
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Abstract Light adaptation enables the vertebrate visual system to operate over a wide range of ambient illumination. Regulation of phototransduction in photoreceptors is considered a major mechanism underlying light adaptation. However, various types of neurons and glial cells exist in the retina, and whether and how all retinal cells interact to adapt to light/dark conditions at the cellular and molecular levels requires systematic investigation. Therefore, we utilized single-cell RNA sequencing to dissect retinal cell-type-specific transcriptomes during light/dark adaptation in mice. The results demonstrated that, in addition to photoreceptors, other retinal cell types also showed dynamic molecular changes and specifically enriched signaling pathways under light/dark adaptation. Importantly, Müller glial cells (MGs) were identified as hub cells for intercellular interactions, displaying complex cell‒cell communication with other retinal cells. Furthermore, light increased the transcription of the deiodinase Dio2 in MGs, which converted thyroxine (T4) to active triiodothyronine (T3). Subsequently, light increased T3 levels and regulated mitochondrial respiration in retinal cells in response to light conditions. As cones specifically express the thyroid hormone receptor Thrb, they responded to the increase in T3 by adjusting light responsiveness. Loss of the expression of Dio2 specifically in MGs decreased the light responsive ability of cones. These results suggest that retinal cells display global transcriptional changes under light/dark adaptation and that MGs coordinate intercellular communication during light/dark adaptation via thyroid hormone signaling.
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| Keywords
single cell
Müller glial cells
intercellular communication
light/dark adaptation
thyroid hormone signaling
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Corresponding Author(s):
Yuqian Ma,Kun Qu,Mei Zhang,Tian Xue
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Issue Date: 26 September 2023
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