An Lgr5-independent developmental lineage is involved in mouse intestinal regeneration.

IF 3.7 2区生物学 Q1 DEVELOPMENTAL BIOLOGY

Development Pub Date : 2025-02-27 DOI:10.1242/dev.204654

Maryam Marefati, Valeria Fernandez-Vallone, Morgane Leprovots, Gabriella Vasile, Frédérick Libert, Anne Lefort, Gilles Dinsart, Achim Weber, Jasna Jetzer, Marie-Isabelle Garcia, Gilbert Vassart

引用次数: 0

Abstract

Collagenase/dispase treatment of intestinal tissue from adult mice generates cells growing in matrigel as stably replatable cystic spheroids in addition to differentiated organoids. Contrary to classical EDTA-derived organoids, these spheroids display poor intestinal differentiation and are independent of Rspondin/Noggin/EGF for growth. Their transcriptome resembles strikingly that of fetal intestinal spheroids, with downregulation of crypt base columnar cell (CBC) markers (Lgr5, Ascl2, Smoc2, Olfm4). In addition, they display upregulation of inflammatory and mesenchymal genetic programs, together with robust expression of YAP target genes. Lineage tracing, cell-sorting and single cell RNA sequencing experiments demonstrate that adult spheroid-generating cells belong to a hitherto undescribed developmental lineage, independent of Lgr5+ve CBCs, and are involved in regeneration of the epithelium following CBC ablation.

查看原文本刊更多论文

一个不依赖lgr5的发育谱系参与了小鼠肠道再生。

成年小鼠肠道组织的胶原酶/疾病处理产生的细胞除了分化的类器官外，还在基质中生长为稳定可移植的囊性球体。与经典的edta衍生类器官相反，这些球体显示出较差的肠道分化，并且不依赖于Rspondin/Noggin/EGF的生长。它们的转录组与胎儿小肠球体的转录组非常相似，隐窝基柱状细胞（CBC）标记物（Lgr5, Ascl2, Smoc2, Olfm4）下调。此外，它们还表现出炎症和间质遗传程序的上调，以及YAP靶基因的强烈表达。谱系追踪、细胞分选和单细胞RNA测序实验表明，成年球形生成细胞属于迄今为止未描述的发育谱系，独立于Lgr5+ve CBCs，并参与CBC消融后上皮的再生。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Development 生物-发育生物学

CiteScore

6.70

自引率

4.30%

发文量

433

审稿时长

3 months

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.