The Lgr5 intestinal stem cell signature: robust expression of proposed quiescent '+4' cell markers.

IF: 14.012

Cited by: 596

Abstract

Two types of stem cells are currently defined in small intestinal crypts: cycling crypt base columnar (CBC) cells and quiescent '+4' cells. Here, we combine transcriptomics with proteomics to define a definitive molecular signature for Lgr5(+) CBC cells. Transcriptional profiling of FACS-sorted Lgr5(+) stem cells and their daughters using two microarray platforms revealed an mRNA stem cell signature of 384 unique genes. Quantitative mass spectrometry on the same cell populations identified 278 proteins enriched in intestinal stem cells. The mRNA and protein data sets showed a high level of correlation and a combined signature of 510 stem cell-enriched genes was defined. Spatial expression patterns were further characterized by mRNA in-situ hybridization, revealing that approximately half of the genes were expressed in a gradient with highest levels at the crypt bottom, while the other half was expressed uniquely in Lgr5(+)stem cells. Lineage tracing using a newly established knock-in mouse for one of the signature genes, Smoc2, confirmed its stem cell specificity. Using this resource, we find-and confirm by independent approaches-that the proposed quiescent/'+4' stem cell markers Bmi1, Tert, Hopx and Lrig1 are robustly expressed in CBC cells.

Keywords

Spatial Omics

Spatial Gene Expression

MeSH terms

Animals

Antigens, Differentiation

Calcium-Binding Proteins

Gene Expression Profiling

Gene Expression Regulation

Intestinal Mucosa

Intestines

Mice

Mice, Transgenic

Oligonucleotide Array Sequence Analysis

RNA, Messenger

Receptors, G-Protein-Coupled

Stem Cells

Authors

Muñoz, Javier

Stange, Daniel E

Schepers, Arnout G

van de Wetering, Marc

Koo, Bon-Kyoung

Itzkovitz, Shalev

Volckmann, Richard

Kung, Kevin S

Koster, Jan

Radulescu, Sorina

Myant, Kevin

Versteeg, Rogier

Sansom, Owen J

van Es, Johan H

Barker, Nick

van Oudenaarden, Alexander

Mohammed, Shabaz

Heck, Albert J R

Clevers, Hans

Recommend literature

1. Single-molecule transcript counting of stem-cell markers in the mouse intestine.

2. Complementarity of medium-throughput in situ RNA hybridization and tissue-specific transcriptomics: case study of Arabidopsis seed development kinetics.

3. Spatio-temporal expression profile of stem cell-associated gene LGR5 in the intestine during thyroid hormone-dependent metamorphosis in Xenopus laevis.

4. Lgr5+ telocytes are a signaling source at the intestinal villus tip.

5. Imaging individual mRNA molecules using multiple singly labeled probes.

Similar data

1. COMPARATIVE TRANSCRIPTOMIC AND PROTEOMIC ANALYSIS OF LGR5+ve STEM CELLS AND THEIR DAUGHTERS

2. Gene expression profiling along the intestinal crypt axis.

3. Active Lgr5 Positive Stem Cells Drive Self-Renewal in the Pyloric Stomach and Efficiently Build Pyloric Units In-vitro

4. Dynamic Reorganization of Chromatin Accessibility Signatures during Dedifferentiation of Secretory Precursors into Lgr5+ Intestinal Stem Cells

5. Injury-inducible stem cell potential of the intestinal enteroendocrine lineage: single-cell mRNA-seq profiling