PMID- 30270040 OWN - NLM STAT- MEDLINE DCOM- 20190729 LR - 20190729 IS - 1097-4172 (Electronic) IS - 0092-8674 (Linking) VI - 175 IP - 4 DP - 2018 Nov 1 TI - Spatial Reconstruction of Single Enterocytes Uncovers Broad Zonation along the Intestinal Villus Axis. PG - 1156-1167.e15 LID - S0092-8674(18)31164-4 [pii] LID - 10.1016/j.cell.2018.08.063 [doi] AB - The intestinal epithelium is a highly structured tissue composed of repeating crypt-villus units. Enterocytes perform the diverse tasks of absorbing a wide range of nutrients while protecting the body from the harsh bacterium-rich environment. It is unknown whether these tasks are spatially zonated along the villus axis. Here, we extracted a large panel of landmark genes characterized by transcriptomics of laser capture microdissected villus segments and utilized it for single-cell spatial reconstruction, uncovering broad zonation of enterocyte function along the villus. We found that enterocytes at villus bottoms express an anti-bacterial gene program in a microbiome-dependent manner. They next shift to sequential expression of carbohydrates, peptides, and fat absorption machineries in distinct villus compartments. Finally, they induce a Cd73 immune-modulatory program at the villus tips. Our approach can be used to uncover zonation patterns in other organs when prior knowledge of landmark genes is lacking. CI - Copyright (c) 2018 Elsevier Inc. All rights reserved. FAU - Moor, Andreas E AU - Moor AE AD - Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel. Electronic address: andreas.moor@weizmann.ac.il. FAU - Harnik, Yotam AU - Harnik Y AD - Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel. FAU - Ben-Moshe, Shani AU - Ben-Moshe S AD - Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel. FAU - Massasa, Efi E AU - Massasa EE AD - Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel. FAU - Rozenberg, Milena AU - Rozenberg M AD - Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel. FAU - Eilam, Raya AU - Eilam R AD - Department of Veterinary Resources, Weizmann Institute of Science, Rehovot, Israel. FAU - Bahar Halpern, Keren AU - Bahar Halpern K AD - Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel. FAU - Itzkovitz, Shalev AU - Itzkovitz S AD - Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel. Electronic address: shalev.itzkovitz@weizmann.ac.il. LA - eng GR - HHMI/Howard Hughes Medical Institute/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20180927 PL - United States TA - Cell JT - Cell JID - 0413066 CIN - Nat Rev Gastroenterol Hepatol. 2018 Dec;15(12):717. doi: 10.1038/s41575-018-0080-z. PMID: 30361614 MH - Animals MH - Cell Differentiation MH - Cell Movement MH - Enterocytes/cytology/*metabolism/physiology MH - Male MH - Mice MH - Mice, Inbred C57BL MH - Single-Cell Analysis MH - *Transcriptome OTO - NOTNLM OT - metabolism OT - mucosal immunology OT - single-cell transcriptomics OT - spatial transcriptomics OT - systems biology EDAT- 2018/10/03 06:00 MHDA- 2019/07/30 06:00 CRDT- 2018/10/02 06:00 PHST- 2018/05/28 00:00 [received] PHST- 2018/07/29 00:00 [revised] PHST- 2018/08/29 00:00 [accepted] PHST- 2018/10/03 06:00 [pubmed] PHST- 2019/07/30 06:00 [medline] PHST- 2018/10/02 06:00 [entrez] AID - S0092-8674(18)31164-4 [pii] AID - 10.1016/j.cell.2018.08.063 [doi] PST - ppublish SO - Cell. 2018 Nov 1;175(4):1156-1167.e15. doi: 10.1016/j.cell.2018.08.063. Epub 2018 Sep 27.