General Information
- Project ID
- OEP000370
- Project Name
- Integrin αEβ7+ T cells direct intestinal stem cell fate decisions via adhesion signaling
- Description
- Intestinal stem cell (ISC) differentiation is regulated precisely by a niche in the crypt, where lymphocytes may interact with stem and transient amplifying (TA) cells. However, whether and how lymphocyte-stem/TA cell contact affects ISC differentiation is largely unknown. Here, we uncover a novel role of T cell-stem/TA cell contact in ISC fate decisions. We show that intestinal lymphocyte depletion results in skewed ISC differentiation in mice, which can be rescued by T cell transfer. Mechanistically, integrin αEβ7 expressed on T cells binds to E-cadherin on ISCs and TA cells, triggering E-cadherin endocytosis and the consequent Wnt and Notch signaling alterations. Blocking αEβ7—E-cadherin adhesion suppresses Wnt signaling and promotes Notch signaling in ISCs and TA cells, leading to defective ISC differentiation. Thus, αEβ7+ T cells regulate ISC differentiation at single-cell level through cell-cell contact-mediated αEβ7—E-cadherin adhesion signaling, highlighting a critical role of the T cell-stem/TA cell contact in maintaining intestinal homeostasis.
- Publications
-
Integrin αEβ7+ T cells direct intestinal stem cell fate decisions via adhesion signaling
Chen S, Zheng Y, Ran X et al. Integrin αEβ7+ T cells direct intestinal stem cell fate decisions via adhesion signaling. Cell Res (2021).
(PMID: 34518654) (DOI: 10.1038/s41422-021-00561-2)
Project information
- Experiments
- 1
Experiment ID Experiment name Experiment type Create Date OEX001784 Mouse intestinal epithelial cell ScRNA-seq Transcriptomic 2019-06-26 - Samples
- 9
Sample ID Sample Name Sample Subject Type Organism Tissue Create Date OES019019 WT-3 Animalia Mus musculus Small intestine 2019-07-02 OES019020 Itgb7 KO-3 Animalia Mus musculus Small intestine 2019-07-02 OES019021 Itgb7 KO-2 Animalia Mus musculus Small intestine 2019-07-02 OES019022 WT-2 Animalia Mus musculus small intestine 2019-07-02 OES111142 WT-1 Animalia Mus musculus Small intestine 2021-08-12 OES111143 Itgb7 KO-1 Animalia Mus musculus Small intestine 2021-08-12 OES111144 T cell transfer-1 Animalia Mus musculus Small intestine 2021-08-12 OES111145 T cell transfer-2 Animalia Mus musculus Small intestine 2021-08-12 OES111146 T cell transfer-3 Animalia Mus musculus Small intestine 2021-08-12 - Runs
-
9
Run ID Run Name Experiment Sample Data Num Create Date OER032610 19X005 OEX001784 OES019019 8 2019-07-02 OER032611 18X100 OEX001784 OES019021 8 2019-07-02 OER032612 18X098 OEX001784 OES111143 8 2019-07-02 OER032613 18X101 OEX001784 OES019022 8 2019-07-02 OER220060 20X014 OEX001784 OES111146 8 2021-08-17 OER220061 20X013 OEX001784 OES111145 8 2021-08-17 OER220062 20X006 OEX001784 OES019020 8 2021-08-17 OER220063 20X007 OEX001784 OES111144 8 2021-08-17 OER220064 18X099 OEX001784 OES111142 8 2021-08-17
Author Information
- Create Date
- 2019-06-26
- Last Modified
- 2021-09-14
- Submission
- Shiyang Chen
- Center for Excellence in Molecular Cell Science