Graded BMP signaling within intestinal crypt architecture directs self-organization of the Wnt-secreting stem cell niche.
Cell Stem Cell
; 30(4): 433-449.e8, 2023 04 06.
Article
em En
| MEDLINE
| ID: mdl-37028407
ABSTRACT
Signals from the surrounding niche drive proliferation and suppress differentiation of intestinal stem cells (ISCs) at the bottom of intestinal crypts. Among sub-epithelial support cells, deep sub-cryptal CD81+ PDGFRAlo trophocytes capably sustain ISC functions ex vivo. Here, we show that mRNA and chromatin profiles of abundant CD81- PDGFRAlo mouse stromal cells resemble those of trophocytes and that both populations provide crucial canonical Wnt ligands. Mesenchymal expression of key ISC-supportive factors extends along a spatial and molecular continuum from trophocytes into peri-cryptal CD81- CD55hi cells, which mimic trophocyte activity in organoid co-cultures. Graded expression of essential niche factors is not cell-autonomous but dictated by the distance from bone morphogenetic protein (BMP)-secreting PDGFRAhi myofibroblast aggregates. BMP signaling inhibits ISC-trophic genes in PDGFRAlo cells near high crypt tiers; that suppression is relieved in stromal cells near and below the crypt base, including trophocytes. Cell distances thus underlie a self-organized and polar ISC niche.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Nicho de Células-Tronco
/
Mucosa Intestinal
Limite:
Animals
Idioma:
En
Ano de publicação:
2023
Tipo de documento:
Article