Back

Guardian crypt-base-goblet-cells protect the human colonic stem cell niche by triggering cholinergic calcium signal-dependent MUC2 secretion and luminal flushing

Pelaez-Llaneza, N.; Jones, V.; Kam, C.; Lee, A.; Parris, A.; Tattan, S.; Loader, M.; Champion, J.; Russam, G.; Miller, B.; Juge, N.; Wharton, R.; Speakman, C.; Kapur, S.; Hernon, J.; Stearns, A.; Shaik, I.; Pal, A.; Tsigka, A.; Batsoulis, D.; Williams, M. R.

2022-01-04 cell biology
10.1101/2022.01.04.474646 bioRxiv
Show abstract

Mucus secreting goblet cells play a vital role in the maintenance of tissue homeostasis. Here we report the discovery of an enigmatic mechanism for the generation of calcium signals that couple cholinergic input to secretion of hydrated mucus in the human colonic stem cell niche. Mechanistic insights for this study were derived from native human colonic crypts and crypt-like organoids expressing MUC2-mNEON. Importantly, we demonstrate that the human colonic stem cell niche is also a cholinergic niche, and that activation of muscarinic receptors initiates calcium signals at the apical pole of intestinal stem cells and neighbouring crypt-base-goblet-cells. The calcium signal trigger zone is defined by a microdomain of juxtaposed calcium stores expressing TPC1 and InsP3R3 calcium channels. Co-activation of TPC1 and InsP3R3 is required for generation of cholinergic calcium signals and downstream secretion of hydrated mucus, which culminates in the flushing of the colonic stem cell niche.

Matching journals

The top 6 journals account for 50% of the predicted probability mass.

1
Nature Communications
○ 5641 papers in training set
Top 6%
22.9%
Similar papers in this journal
2
Gastroenterology
○ 42 papers in training set
Top 0.1%
8.1%
Similar papers in this journal
3
Cellular and Molecular Gastroenterology and Hepatology
○ 46 papers in training set
Top 0.1%
8.1%
Similar papers in this journal
4
eLife
● 5828 papers in training set
Top 21%
5.6%
Similar papers in this journal
5
Nature
○ 645 papers in training set
Top 3%
5.0%
Similar papers in this journal
6
The EMBO Journal
○ 309 papers in training set
Top 1%
3.5%
50% of probability mass above
7
Science Advances
● 1243 papers in training set
Top 11%
3.2%
8
Cell Reports
○ 1498 papers in training set
Top 14%
2.5%
9
iScience
○ 1154 papers in training set
Top 11%
2.4%
10
Cell Stem Cell
○ 62 papers in training set
Top 0.7%
2.2%
11
Nature Cell Biology
○ 118 papers in training set
Top 2%
1.8%
12
Communications Biology
○ 993 papers in training set
Top 13%
1.8%
13
Proceedings of the National Academy of Sciences
● 2444 papers in training set
Top 27%
1.7%
14
Advanced Science
○ 286 papers in training set
Top 5%
1.5%
15
EMBO Reports
○ 263 papers in training set
Top 4%
1.4%
16
Scientific Reports
○ 3612 papers in training set
Top 59%
1.4%
17
Life Science Alliance
● 285 papers in training set
Top 5%
1.2%
18
Cell
○ 431 papers in training set
Top 7%
1.2%
19
Developmental Cell
○ 196 papers in training set
Top 3%
1.2%
20
JCI Insight
● 277 papers in training set
Top 6%
1.0%
21
Current Biology
○ 665 papers in training set
Top 9%
1.0%
22
Gut Microbes
○ 78 papers in training set
Top 1%
0.9%
23
Nature Medicine
○ 125 papers in training set
Top 3%
0.9%
24
PLOS Biology
● 486 papers in training set
Top 13%
0.6%
25
Stem Cell Reports
○ 130 papers in training set
Top 2%
0.6%

"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.