Neil McCarthy, Camila Mendez Jimenez, Guodong Tie, Gizelle McCarthy, Shariq Madha-Krause, Ruiyang He, Ramesh A Shivdasani
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引用次数: 0
Abstract
When intestinal stem cells (ISCs) are damaged, other epithelial cells de-differentiate to restore the ISC compartment. Immune, nerve and lymphatic endothelial cells contribute signals that promote this response, but it is unclear whether or how the native mesenchymal niche senses and responds to ISC loss. In homeostasis, trophocytes and smooth muscle beneath intestinal crypts secrete BMP inhibitors (BMPi) and R-spondins to foster ISC self-renewal, whereas sub-epithelial myofibroblasts (SEMFs) concentrated at crypt tops promote differentiation through bone morphogenetic proteins (BMPs). We assessed transcriptional responses in mouse sub-epithelial populations after ablating ISCs with whole-body irradiation and treating Lgr5DTR mice with diphtheria toxin. More than any other cell type, SEMFs modulated expression of genes related to ISC expansion. However, the BMPi gene Smoc1 and non-canonical Wnt signals, both expressed in SEMFs after whole-body irradiation, were dispensable for ISC restoration. Instead, SEMFs appear to support ISC regeneration through factors that are not induced by ISC attrition per se but by local inflammation. These findings reveal unexpectedly limited transcriptional modulation of the native niche after ISC losses and context-dependent signaling functions for SEMFs.
期刊介绍：
Development’s scope covers all aspects of plant and animal development, including stem cell biology and regeneration. The single most important criterion for acceptance in Development is scientific excellence. Research papers (articles and reports) should therefore pose and test a significant hypothesis or address a significant question, and should provide novel perspectives that advance our understanding of development. We also encourage submission of papers that use computational methods or mathematical models to obtain significant new insights into developmental biology topics. Manuscripts that are descriptive in nature will be considered only when they lay important groundwork for a field and/or provide novel resources for understanding developmental processes of broad interest to the community.
Development includes a Techniques and Resources section for the publication of new methods, datasets, and other types of resources. Papers describing new techniques should include a proof-of-principle demonstration that the technique is valuable to the developmental biology community; they need not include in-depth follow-up analysis. The technique must be described in sufficient detail to be easily replicated by other investigators. Development will also consider protocol-type papers of exceptional interest to the community. We welcome submission of Resource papers, for example those reporting new databases, systems-level datasets, or genetic resources of major value to the developmental biology community. For all papers, the data or resource described must be made available to the community with minimal restrictions upon publication.
To aid navigability, Development has dedicated sections of the journal to stem cells & regeneration and to human development. The criteria for acceptance into these sections is identical to those outlined above. Authors and editors are encouraged to nominate appropriate manuscripts for inclusion in one of these sections.
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