20
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Single-cell transcriptome analysis reveals differential nutrient absorption functions in human intestine

      research-article

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Single-cell transcriptome analysis of epithelial cells from human ileum, colon, and rectum reveals different nutrient-absorption preferences in the small and large intestine, providing a rich resource for further characterization of human intestine cell constitution and functions.

          Abstract

          The intestine plays an important role in nutrient digestion and absorption, microbe defense, and hormone secretion. Although major cell types have been identified in the mouse intestinal epithelium, cell type–specific markers and functional assignments are largely unavailable for human intestine. Here, our single-cell RNA-seq analyses of 14,537 epithelial cells from human ileum, colon, and rectum reveal different nutrient absorption preferences in the small and large intestine, suggest the existence of Paneth-like cells in the large intestine, and identify potential new marker genes for human transient-amplifying cells and goblet cells. We have validated some of these insights by quantitative PCR, immunofluorescence, and functional analyses. Furthermore, we show both common and differential features of the cellular landscapes between the human and mouse ilea. Therefore, our data provide the basis for detailed characterization of human intestine cell constitution and functions, which would be helpful for a better understanding of human intestine disorders, such as inflammatory bowel disease and intestinal tumorigenesis.

          Graphical Abstract

          Related collections

          Most cited references42

          • Record: found
          • Abstract: found
          • Article: not found

          Bidirectional transport of amino acids regulates mTOR and autophagy.

          Amino acids are required for activation of the mammalian target of rapamycin (mTOR) kinase which regulates protein translation, cell growth, and autophagy. Cell surface transporters that allow amino acids to enter the cell and signal to mTOR are unknown. We show that cellular uptake of L-glutamine and its subsequent rapid efflux in the presence of essential amino acids (EAA) is the rate-limiting step that activates mTOR. L-glutamine uptake is regulated by SLC1A5 and loss of SLC1A5 function inhibits cell growth and activates autophagy. The molecular basis for L-glutamine sensitivity is due to SLC7A5/SLC3A2, a bidirectional transporter that regulates the simultaneous efflux of L-glutamine out of cells and transport of L-leucine/EAA into cells. Certain tumor cell lines with high basal cellular levels of L-glutamine bypass the need for L-glutamine uptake and are primed for mTOR activation. Thus, L-glutamine flux regulates mTOR, translation and autophagy to coordinate cell growth and proliferation.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Canonical correlation analysis: an overview with application to learning methods.

            We present a general method using kernel canonical correlation analysis to learn a semantic representation to web images and their associated text. The semantic space provides a common representation and enables a comparison between the text and images. In the experiments, we look at two approaches of retrieving images based on only their content from a text query. We compare orthogonalization approaches against a standard cross-representation retrieval technique known as the generalized vector space model.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Tales from the crypt: new insights into intestinal stem cells

              The intestinal epithelium withstands continuous mechanical, chemical and biological insults despite its single-layered, simple epithelial structure. The crypt-villus tissue architecture in combination with rapid cell turnover enables the intestine to act both as a barrier and as the primary site of nutrient uptake. Constant tissue replenishment is fuelled by continuously dividing stem cells that reside at the bottom of crypts. These cells are nurtured and protected by specialized epithelial and mesenchymal cells, and together constitute the intestinal stem cell niche. Intestinal stem cells and early progenitor cells compete for limited niche space and, therefore, the ability to retain or regain stemness. Those cells unable to do so differentiate to one of six different mature cell types and move upwards towards the villus, where they are shed into the intestinal lumen after 3-5 days. In this Review, we discuss the signals, cell types and mechanisms that control homeostasis and regeneration in the intestinal epithelium. We investigate how the niche protects and instructs intestinal stem cells, which processes drive differentiation of mature cells and how imbalance in key signalling pathways can cause human disease.
                Bookmark

                Author and article information

                Journal
                J Exp Med
                J. Exp. Med
                jem
                jem
                The Journal of Experimental Medicine
                Rockefeller University Press
                0022-1007
                1540-9538
                3 February 2020
                21 November 2019
                : 217
                : 2
                : e20191130
                Affiliations
                [1 ]The State Key Laboratory of Membrane Biology, Tsinghua-Peking Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing, China
                [2 ]The MOE Key Laboratory of Bioinformatics, Center for Synthetic & Systems Biology, School of Life Sciences, Tsinghua University, Beijing, China
                [3 ]Department of General Surgery, Peking University Third Hospital, Beijing, China
                [4 ]Max-Planck Center for Tissue Stem Cell Research and Regenerative Medicine, Guangzhou Regenerative Medicine and Health Guangdong Laboratory, Guangzhou, China
                Author notes
                Correspondence to Ye-Guang Chen: ygchen@ 123456tsinghua.edu.cn
                [*]

                Y. Wang and W. Song contributed equally to this paper.

                Author information
                https://orcid.org/0000-0003-2785-0534
                https://orcid.org/0000-0002-6701-0065
                Article
                20191130
                10.1084/jem.20191130
                7041720
                31753849
                7e34961a-3d26-4e48-a7f3-18edbdb95797
                © 2019 Wang et al.

                This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms/). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/).

                History
                : 20 June 2019
                : 28 August 2019
                : 18 October 2019
                Page count
                Pages: 15
                Funding
                Funded by: National Key Research and Development Program of China
                Award ID: 2017YFA0103601
                Award ID: 2016YFC0906001
                Funded by: National Natural Science Foundation of China, DOI https://doi.org/10.13039/501100001809;
                Award ID: 31330049
                Award ID: 81472855
                Award ID: 91540109
                Categories
                Research Articles
                Technical Advances and Resources
                308

                Medicine
                Medicine

                Comments

                Comment on this article