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Cited by 361

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Distinct Mesenchymal Cell Populations Generate the Essential Intestinal BMP Signaling Gradient

Open access
McCarthy, Neil, Manieri, Elisa, Storm, Elaine E., Saadatpour, Assieh, Luoma, Adrienne M., Kapoor, Varun N., Madha, Shariq, Gaynor, Liam T., Cox, Christian, Keerthivasan, Shilpa, Wucherpfennig, Kai, Yuan, Guo-Cheng, de Sauvage, Frederic J., Turley, Shannon J., Shivdasani, Ramesh A.·2020·Cell Stem Cell

Abstract

SUMMARY Intestinal stem cells (ISCs) are confined to crypt bottoms and their progeny differentiate near crypt-villus junctions. Wnt and bone morphogenic protein (BMP) gradients drive this polarity, and colorectal cancer fundamentally reflects disruption of this homeostatic signaling. However, sub-epithelial sources of crucial agonists and antagonists that organize this BMP gradient remain obscure. Here, we couple whole-mount high-resolution microscopy with ensemble and single-cell RNA sequencing (RNA-seq) to identify three distinct PDGFRA+ mesenchymal cell types. PDGFRA(hi) telocytes are especially abundant at the villus base and provide a BMP reservoir, and we identified a CD81+ PDGFRA(lo) population present just below crypts that secretes the BMP antagonist Gremlin1. These cells, referred to as trophocytes, are sufficient to expand ISCs in vitro without additional trophic support and contribute to ISC maintenance in vivo. This study reveals intestinal mesenchymal structure at fine anatomic, molecular, and functional detail and the cellular basis for a signaling gradient necessary for tissue self-renewal.

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Crossref · 10.1016/j.stem.2020.01.008

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Metadata

Authors
McCarthy, N., Manieri, E., Storm, E. E., Saadatpour, A., Luoma, A. M., Kapoor, V. N., Madha, S., Gaynor, L. T., Cox, C., Keerthivasan, S., Wucherpfennig, K., Yuan, G.-C., de Sauvage, F. J., Turley, S. J., & Shivdasani, R. A.
Venue
Cell Stem Cell
Publisher
Elsevier BV
Published
2020-03
Volume
26
Issue
3
Pages
391-402.e5
ISSN
  • 1875-9777 (ISSN-L)
  • 1934-5909
OpenAlex
W3008165945
Cited by
361
References
72
FWCI
13.35
Type
journal article
Language
en
Open access
bronze

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CoChat. (2026). Citation check: Distinct Mesenchymal Cell Populations Generate the Essential Intestinal BMP Signaling Gradient. https://app.cochat.ai/papers/10.1016/j.stem.2020.01.008
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McCarthy, N., Manieri, E., Storm, E. E., Saadatpour, A., Luoma, A. M., Kapoor, V. N., Madha, S., Gaynor, L. T., Cox, C., Keerthivasan, S., Wucherpfennig, K., Yuan, G.-C., de Sauvage, F. J., Turley, S. J., & Shivdasani, R. A. (2020). Distinct Mesenchymal Cell Populations Generate the Essential Intestinal BMP Signaling Gradient. Cell Stem Cell. https://doi.org/10.1016/j.stem.2020.01.008

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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).

Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.