BMP gradient along the intestinal villus axis controls zonated enterocyte and goblet cell states

Beumer, Joep; Puschhof, Jens; Yengej, Fjodor Yousef; Zhao, Lianzheng; Martínez-Silgado, Adriana; Blotenburg, Marloes; Begthel, Harry; Boot, Charelle; Oudenaarden, Alexander van; Chen, Ye‐Guang

doi:10.1016/j.celrep.2022.110438

Cited by 64 publications

(61 citation statements)

References 57 publications

(80 reference statements)

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“…They may also include subepithelial myofibroblasts, as they express αSMA ( 5 , 13 ). The expression of BMPs and their location suggests an important function in epithelial cell differentiation ( 26 – 28 ). Therefore, the relative location of CD81 + and PDGFRα hi fibroblast subsets contributes to the generation of a signaling gradient along the small intestinal villous-crypt and colonic crypt top-bottom axis that facilitates ISC maintenance and differentiation ( 5 ).…”

Section: Main Textmentioning

confidence: 99%

Fibroblasts in intestinal homeostasis, damage, and repair

2022

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The mammalian intestine is a self-renewing tissue that ensures nutrient absorption while acting as a barrier against environmental insults. This is achieved by mature intestinal epithelial cells, the renewing capacity of intestinal stem cells at the base of the crypts, the development of immune tolerance, and the regulatory functions of stromal cells. Upon intestinal injury or inflammation, this tightly regulated mucosal homeostasis is disrupted and is followed by a series of events that lead to tissue repair and the restoration of organ function. It is now well established that fibroblasts play significant roles both in the maintenance of epithelial and immune homeostasis in the intestine and the response to tissue damage mainly through the secretion of a variety of soluble mediators and ligands and the remodeling of the extracellular matrix. In addition, recent advances in single-cell transcriptomics have revealed an unexpected heterogeneity of fibroblasts that comprise distinct cell subsets in normal and inflammatory conditions, indicative of diverse functions. However, there is still little consensus on the number, terminology, and functional properties of these subsets. Moreover, it is still unclear how individual fibroblast subsets can regulate intestinal repair processes and what is their impact on the pathogenesis of inflammatory bowel disease. In this mini-review, we aim to provide a concise overview of recent advances in the field, that we believe will help clarify current concepts on fibroblast heterogeneity and functions and advance our understanding of the contribution of fibroblasts in intestinal damage and repair.

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Section: Main Textmentioning

confidence: 99%

Fibroblasts in intestinal homeostasis, damage, and repair

2022

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“…The BMP pathway counteracts the pro-stem and pro-proliferative effects of the Wnt pathway, regulating cell differentiation and apoptosis in intestinal homeostasis. 64,65 BMP ligands are members of the transforming growth factor-β (TGFβ) signaling family. 66 They have crucial roles during embryogenesis, mainly in mesoderm formation, cardiac and bone development.…”

Section: Regulating Intestinal Epithelial Cell Fatementioning

confidence: 99%

The emerging era of personalized medicine in advanced colorectal cancer

Reid

Leedham

et al. 2022

J of Gastro and Hepatol

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Colorectal cancer (CRC) is a genetically heterogeneous disease with its pathogenesis often driven by varying genetic or epigenetic alterations. This has led to a substantial number of patients developing chemoresistance and treatment failure, resulting in a high mortality rate for advanced disease. Deep molecular analysis has allowed for the discovery of key intestinal signaling pathways which impacts colonic epithelial cell fate, and the integral role of the tumor microenvironment on cancer growth and dissemination. Through transitioning pre‐clinical knowledge in research into clinical practice, many potential druggable targets within these pathways have been discovered in the hopes of overcoming the roadblocks encountered by conventional therapies. A personalized approach tailoring treatment according to the histopathological and molecular features of individual tumors can hopefully translate to better patient outcomes, and reduce the rate of recurrence in patients with advanced CRC. Herein, the latest understanding on the molecular science behind CRC tumorigenesis, and the potential treatment targets currently at the forefront of research are summarized.

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“…The changing environment along the crypt-villus axis guides both differentiation and functional subspecialization of differentiated cells. ( Beumer et al., 2018 , 2022 ; Moor et al., 2018 ; Beumer and Clevers, 2021 ).…”

Section: Before You Beginmentioning

confidence: 99%

“…Using transient overexpression of the transcription factor Neurogenin-3, we describe the enhancement of differentiation toward rare enteroendocrine cells. For complete details on the use and execution of this protocol, please refer to Beumer et al. (2022) .…”

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confidence: 99%