Functional Niche Research Articles

Snai2 Maintains Bone Marrow Niche Cells by Repressing Osteopontin Expression

Bone marrow (BM) mesenchymal stem and progenitor cells (MSPCs) are a critical constituent of the hematopoietic stem cell (HSC) niche. Previous studies have suggested that the zinc-finger epithelial-mesenchymal transition transcription factor Snai2 (also known as Slug) regulated HSCs autonomously. Here, we show that Snai2 expression in the BM is restricted to the BM stromal compartment where it regulates the HSC niche. Germline or MSPC-selective Snai2 deletion reduces the functional MSPC pool and their mesenchymal lineage output and impairs HSC niche function during homeostasis and after stress. RNA sequencing analysis revealed that Spp1 (osteopontin) expression is markedly upregulated in Snai2-deficient MSPCs. Genetic deletion of Spp1 in Snai2-deficient mice rescues MSPCs' functions. Thus, SNAI2 is a critical regulator of the transcriptional network maintaining MSPCs by the suppression of osteopontin expression.

Immune outposts in the adventitia: One foot in sea and one on shore.

Advances in microscopy, genetically modified mice, and single-cell RNA sequencing have begun to deconvolute the composition and function of tissue immune niches. Here we discuss the evidence that the adventitia, the outermost layer of larger blood vessels, is a conserved niche and tissue immune outpost for multiple immune cells, including group 2 innate lymphoid cells (ILC2) and subsets of tissue-resident memory T cells, macrophages, and dendritic cells. We also describe the unique non-immune composition at adventitial regions, including fibroblast-like stromal cell subsets, lymphatic and blood endothelial cells, and neurons, and review how immune-stromal crosstalk impacts regional tissue immunity, organ adaptation, and disease.

The nitrogen economic spectrum of legume stoichiometry and fixation strategy.

Leaf nitrogen concentration often is higher in leguminous plants, which associate with dinitrogen-fixing bacteria, compared with nonlegume plants. However, the range of nitrogen concentrations in legumes is wide, likely related to the range of nitrogen fixation strategies. We evaluated how carbon and nitrogen allocation to roots, stems and leaves is influenced by the type of strategy of nitrogen fixation regulation. We grew herbaceous annual legumes (Medicago truncatula, Hymenocarpos circinnatus and Vicia palaestina) under two nitrogen availability treatments (none/sufficient), with and without bacterial inoculation. We found facultative downregulation of the rate of nitrogen fixation when nitrogen was available in H.circinnatus, and an obligate similar fixation rate in both nitrogen treatments in M.truncatula and V.palaestina. Uninoculated plants invested more biomass in roots and contained lower nitrogen concentrations. However, nitrogen concentration in the entire plant and in the leaves was lower and more plastic in the species with a facultative fixation strategy, whereas species with an obligate fixation strategy also maintained high nitrogen concentrations. Our results suggest a suite of functional traits associated with the strategies of allocation and symbiotic nitrogen fixation. This suite of traits probably shapes successional and functional niches of different leguminous species in specious plant communities.

Daily Ethanol Drinking Followed by an Abstinence Period Impairs Bone Marrow Niche and Mitochondrial Function of Hematopoietic Stem/Progenitor Cells in Rhesus Macaques.

Unhealthy consumption of alcohol is a major public health crisis with strong associations between immunological dysfunctions, high vulnerability to infectious disease, anemia, and an increase in the risk of hematological malignancies. However, there is a lack of studies addressing alcohol-induced changes in bone marrow (BM) and hematopoiesis as fundamental aspects of immune system function. To address the effect of chronic alcohol consumption on hematopoietic stem and progenitor cells (HSPCs) and the BM niche, we used an established rhesus macaque model of voluntary alcohol drinking. A cohort of young adult male rhesus macaques underwent a standard ethanol self-administration protocol that allowed a choice of drinking alcohol or water 22hours/day with periods of forced abstinence that elevated subsequent intakes when alcohol availability resumed. Following the last month of forced abstinence, the monkeys were euthanized. HSPCs and bone samples were collected and analyzed in functional assays and by confocal microscopy. HSPCs from alcohol animals exhibited reduced ability to formgranulocyte-monocyte and erythroidcolonies in vitro. HSPCs also displayed a decrease in mitochondrial oxygen consumption linked to ATP production and basal respiratory capacity. Chronic alcohol use led to vascular remodeling of the BM niche, a reduction in the number of primitive HSPCs, and a shift in localization of HSPCs from an adipose to a perivascular niche. Our study demonstrates, for the first time, that chronic voluntary alcohol drinking in rhesus macaque monkeys leads to the long-term impairment of HSPC function, a reduction in mitochondrial respiratory activity, and alterations in the BM microenvironment. Further studies are needed to determine whether these changes in hematopoiesis are persistent or adaptive during the abstinent period and whether an initial imprinting to alcohol primes BM to become more vulnerable to future exposure to alcohol.

Linking intraspecific variability in trophic and functional niches along an environmental gradient

Abstract Intraspecific trophic variability has important ecological and evolutionary implications, and is driven by multiple interacting factors. Functional traits and environmental conditions are important in mediating the trophic niche of individuals because they determine their ability to consume certain prey, their energetic requirements, and resource availability. In this study, we aimed at investigating the interacting effects of functional traits and environmental conditions on several attributes of trophic niche in natural populations. Here, we quantified intraspecific variability in the trophic niche of 12 riverine populations of European minnow (Phoxinus phoxinus) using stable isotope analyses. Functional traits (i.e. morpho‐anatomical traits) and environmental conditions (i.e. upstream–downstream gradient, forest cover) were quantified to identify the determinants of (1) trophic position and resource origin, (2) trophic niche size, and (3) trophic differentiation (β‐diversity) among populations. We demonstrated that trophic position and resource origin covaried with functional traits related to body size and locomotion performance, and that the strength and shape of these relationships varied according to local environmental conditions. The trophic niche size also differed among populations, although no determinant was identified. Finally, trophic β‐diversity was correlated to environmental differentiation among sites. Overall, the determinants of intraspecific variability in trophic niche appeared highly context‐dependent, and related to the interactions between functional traits and environmental conditions. Because populations are currently facing important environmental changes, understanding this context‐dependency is important for predicting food web structure and ecosystem dynamics in a changing world.

Identification of Complex Rumen Microbiome Interaction Within Diverse Functional Niches as Mechanisms Affecting the Variation of Methane Emissions in Bovine.

A network analysis including relative abundances of all ruminal microbial genera (archaea, bacteria, fungi, and protists) and their genes was performed to improve our understanding of how the interactions within the ruminal microbiome affects methane emissions (CH4). Metagenomics and CH4 data were available from 63 bovines of a two-breed rotational cross, offered two basal diets. Co-abundance network analysis revealed 10 clusters of functional niches. The most abundant hydrogenotrophic Methanobacteriales with key microbial genes involved in methanogenesis occupied a different functional niche (i.e., “methanogenesis” cluster) than methylotrophic Methanomassiliicoccales (Candidatus Methanomethylophylus) and acetogens (Blautia). Fungi and protists clustered together and other plant fiber degraders like Fibrobacter occupied a seperate cluster. A Partial Least Squares analysis approach to predict CH4 variation in each cluster showed the methanogenesis cluster had the best prediction ability (57.3%). However, the most important explanatory variables in this cluster were genes involved in complex carbohydrate degradation, metabolism of sugars and amino acids and Candidatus Azobacteroides carrying nitrogen fixation genes, but not methanogenic archaea and their genes. The cluster containing Fibrobacter, isolated from other microorganisms, was positively associated with CH4 and explained 49.8% of its variability, showing fermentative advantages compared to other bacteria and fungi in providing substrates (e.g., formate) for methanogenesis. In other clusters, genes with enhancing effect on CH4 were related to lactate and butyrate (Butyrivibrio and Pseudobutyrivibrio) production and simple amino acids metabolism. In comparison, ruminal genes negatively related to CH4 were involved in carbohydrate degradation via lactate and succinate and synthesis of more complex amino acids by γ-Proteobacteria. When analyzing low- and high-methane emitters data in separate networks, competition between methanogens in the methanogenesis cluster was uncovered by a broader diversity of methanogens involved in the three methanogenesis pathways and larger interactions within and between communities in low compared to high emitters. Generally, our results suggest that differences in CH4 are mainly explained by other microbial communities and their activities rather than being only methanogens-driven. Our study provides insight into the interactions of the rumen microbial communities and their genes by uncovering functional niches affecting CH4, which will benefit the development of efficient CH4 mitigation strategies.

Functional Divergence Drives Invasibility of Plant Communities at the Edges of a Resource Availability Gradient

Invasive Alien Species (IAS) are a serious threat to biodiversity, severely affecting natural habitats and species assemblages. However, no consistent empirical evidence emerged on which functional traits or trait combination may foster community invasibility. Novel insights on the functional features promoting community invasibility may arise from the use of mechanistic traits, like those associated with drought resistance, which have been seldom included in trait-based studies. Here, we tested for the functional strategies of native and invasive assemblage (i.e., environmental filtering hypothesis vs. niche divergence), and we assessed how the functional space determined by native species could influence community invasibility at the edges of a resource availability gradient. Our results showed that invasive species pools need to have a certain degree of differentiation in order to persist in highly invaded communities, suggesting that functional niche divergence may foster community invasibility. In addition, resident native communities more susceptible to invasion are those which, on average, have higher resource acquisition capacity, and lower drought resistance coupled with an apparently reduced water-use efficiency. We advocate the use of a mechanistic perspective in future research to comprehensively understand invasion dynamics, providing also new insights on the factors underlying community invasibility in different ecosystems.

"In situ similis" Culturing of Plant Microbiota: A Novel Simulated Environmental Method Based on Plant Leaf Blades as Nutritional Pads.

High-throughput cultivation methods have recently been developed to accelerate the recovery of microorganisms reluctant to cultivation. They simulate in situ environmental conditions for the isolation of environmental microbiota through the exchange of growth substrates during cultivation. Here, we introduce leaf-based culture media adopting the concept of the plant being the master architect of the composition of its microbial community. Pre-physical treatments of sunflower plant leaves, namely punching, freezing, and/or autoclavation, allowed the diffusion of electrolytes and other nutrients to configure the leaf surface as a natural pad, i.e., creating an “in situ similis” environment suitable for the growth of rarely isolated microbiota. We used surface inoculation and membrane-filtration methods to assess the culturability of endophytic bacteria from the sunflower phyllosphere and rhizosphere. Both methods supported excellent colony-forming unit (CFU) development when compared to standard R2A medium, with a special affinity to support better growth of epiphytic and endophytic populations of the phyllosphere compared with the rhizosphere. A 16S rRNA gene analysis of >122 representative isolates indicated the cultivation of a diverse set of microorganisms by application of the new methods. It indicated the predominance of 13 genera of >30 potential species, belonging to Firmicutes, Proteobacteria, and Actinobacteria, and especially genera not commonly reported for sunflower, e.g., Rhizobium, Aureimonas, Sphingomonas, Paracoccus, Stenotrophomonas, Pantoea, Kosakonia, and Erwinia. The strategy successfully extended diversity and richness in the endophyllosphere compared to the endorhizosphere, while CFUs grown on the standard R2A medium mainly pertain to Firmicutes, especially Bacillus spp. MALDI-TOF MS analysis clustered the isolates according to their niche and potential functions, where the majority of isolates of the endorhizosphere were clustered away from those of the endophyllosphere. Isolates identified as Gammaproteobacteria and Alphaproteobacteria were distinguishably sub-clustered, which was in contrast to the heterogeneous isolates of Firmicutes (Bacillus spp.). In conclusion, leaf in situ similis cultivation is an effective strategy to support the future application of culturomics of plant microbiota. This is an effort to access novel isolates that are more adapted and competitive in their natural environments, especially those subjected to abiotic stresses like those prevailing in arid/semi-arid zones, and, consequently, to support the application of agro-biotechnologies, among other technologies, to improving agriculture in such zones.

Bone marrow niche dysregulation in myeloproliferative neoplasms.

The bone marrow niche is a complex and dynamic structure composed of a multitude of cell types which functionally create an interactive network facilitating hematopoietic stem cell development and maintenance. Its specific role in the pathogenesis, response to therapy, and transformation of myeloproliferative neoplasms has only recently been explored. Niche functionality is likely affected not only by the genomic background of the myeloproliferative neoplasm-associated mutated hematopoietic stem cells, but also by disease-associated ‘chronic inflammation’, and subsequent adaptive and innate immune responses. ‘Cross-talk’ between mutated hematopoietic stem cells and multiple niche components may contribute to propagating disease progression and mediating drug resistance. In this timely article, we will review current knowledge surrounding the deregulated bone marrow niche in myeloproliferative neoplasms and suggest how this may be targeted, either directly or indirectly, potentially influencing therapeutic choices both now and in the future.

The Cellular and Physiological Basis for Lung Repair and Regeneration: Past, Present, and Future.

The respiratory system, which includes the trachea, airways, and distal alveoli, is a complex multi-cellular organ that intimately links with the cardiovascular system to accomplish gas exchange. In this review and as members of the NIH/NHLBI-supported Progenitor Cell Translational Consortium, we discuss key aspects of lung repair and regeneration. We focus on the cellular compositions within functional niches, cell-cell signaling in homeostatic health, the responses to injury, and new methods to study lung repair and regeneration. We also provide future directions for an improved understanding of the cell biology of the respiratory system, as well as new therapeutic avenues.

Community-level variation in plant functional traits and ecological strategies shapes habitat structure along succession gradients in alpine environment

Plant traits and ecological strategies elucidate various aspects of ecosystem functioning and services. However, the well-recognized trade-offs evident at the species level are not always expected to mirror community-level variation. Here, we investigated, at the regional scale, the community-level trade-offs of three key plant traits representing economics and size spectra (LA—leaf area, LDMC—leaf dry matter content and SLA—specific leaf area) and Grime’s CSR (competitive, stress tolerant, ruderal) plant strategies. We compared six siliceous alpine plant communities, also representative of Habitat types of EU Community interest (Habitats Directive, 92/43/EEC), distributed along a succession gradient, using a wide range of phytosociological releves for which we calculated community weighted mean (CWM) trait values and C-, S- and R-scores. Our aims were to: (1) determine the validity of the plant community global spectrum of trait variation within alpine habitats; (2) investigate the discriminating capacity of plant traits and strategies to identify functional niches of dominance, stress and disturbance along the succession gradient; (3) quantify the variation in community structure (species richness and total species cover) through such functional niches. We observed a clear pattern of community-level trait variation that reflected the plant economics spectrum: from acquisitive and fast-growing characteristics in pioneer succession stages, to conservative and stress-tolerant features toward the succession climax, while the productive niche typical of C-selected strategies was scarce. Species richness and total species cover were both greater at intermediate levels of S- and R-selection gradients, indicating high niche differentiation in habitats characterized by exposure to stress or disturbance. Overall, this study demonstrates that trait trade-offs between communities identified at the global scale can undergo adaptation at the regional scale caused by local environmental conditions and also confirms the applicability of CSR strategies to investigate community-level variation of alpine vegetation.

Reversibility of the subterranean life-style

The extreme traits of subterranean organisms have traditionally been considered detrimental in the surface environment, thereby permanently restricting them to the dark, fragmented and relatively stable subsurface. Specifically, the loss of eyes and pigment coupled with stenothermy is thought to be disadvantageous in the dynamic surface environment, especially in the face of competition from epigean counterparts. However, this paradigm has been challenged by several recent studies which indicate that in rare cases, a reversal to surface habitats seems likely. Using the amphipod genus Niphargus as a model, I present environmental, life-history, phylogeographic, phylogenetic, trophic and functional morphological data that supports at least two independent reversals to surface environments. The two studied species, N. hrabei and N. valachicus, have rarely been reported from groundwater, but are common inhabitants of surface rivers, streams and lakes. They have very broad geographical distributions (>1300 km) with modest genetic divergence, indicating wide-scale dispersal and gene-flow via the interconnected surface river network. Molecular phylogenies strongly support their independent origin from groundwater ancestors. In the case of N. valachicus, life-history data further supports an epigean lifestyle due to the strong influence of seasonality, closely matching the patterns observed in surface amphipods. A comparison of functional morphology and trophic niche between this species and two of its most common sympatric surface relatives (Gammarus dacicus and Synurella ambulans) reveals that it occupies a unique predatory niche, indicating little trophic overlap and decreased competitive pressure. It therefore appears that, under certain circumstances, subterranean species do not only recolonize, but also thrive in surface environments.

Functional diversity of tree cavities for secondary cavity-nesting birds in logged subtropical Piedmont forests of the Andes

Studies about functional ecology have increased in the last years and they are currently an important element for the understanding of ecosystem processes. The aim of this study was to compare different functional traits of cavity trees for secondary cavity-nesting birds, between unlogged (control forest) and conventionally logged sites in subtropical piedmont forests of NW Argentina. Between 10 and 20 plots per site were established and were grouped according to the treatments (control forest and logged forest) for statistical analyses. We measured and defined the following cavity tree traits potentially important for cavity-nesting birds: diameter at breast height (DBH), cavity height, cavity entrance size and cavity internal depth. Besides, abundance and taxonomic richness of cavity tree species were calculated, as well as functional indices: Functional Richness (FRic, amount of functional niche volume filled by cavity tree species in the community), Functional Evenness (FEve, measures the regularity of the distribution of cavity tree species abundances and dissimilarities in functional space), Functional Divergence (FDiv, quantifies how cavity tree species diverge in their abundance-weighted, distances in functional space) and Community-Weighted Mean (CWM, mean of trait values present in the community weighted by the relative abundance of species bearing each value). The main results showed that logged sites (relative to control sites) had: (1) lower abundance and taxonomic richness of cavity trees; (2) lower functional richness; (3) higher functional evenness, which may be due to the uniformity in distribution of the traits of the cavity tree species in space; (4) lower ‘Community-Weighted Mean’ of cavity size, possibly due to the fact that larger cavities need larger tree species and they are the most extracted in logged sites. Understanding how the functional traits of cavity trees are affected may help decision makers to implement sustainable policies for conservation of secondary-cavity user birds, and consequently, of the ecological services they provide.

Arabidopsis RanBP2-Type Zinc Finger Proteins Related to Chloroplast RNA Editing Factor OZ1.

OZ1, an RNA editing factor that controls the editing of 14 cytidine targets in Arabidopsis chloroplasts, contains two RanBP2-type zinc finger (Znf) domains. The RanBP2 Znf is a C4-type member of the broader zinc finger family with unique functions and an unusually diverse distribution in plants. The domain can mediate interactions with proteins or RNA and appears in protein types such as proteases, RNA editing factors, and chromatin modifiers; however, few characterized Arabidopsis proteins containing RanBP2 Znfs have been studied specifically with the domain in mind. In humans, RanBP2 Znf-containing proteins are involved in RNA splicing, transport, or transcription initiation. We present a phylogenetic overview of Arabidopsis RanBP2 Znf proteins and the functional niches that these proteins occupy in plants. OZ1 and its four-member family represent a branch of this family with major impact on the RNA biology of chloroplasts and mitochondria in Arabidopsis. We discuss what is known about other plant proteins carrying the RanBP2 Znf domain and point out how phylogenetic information can provide clues to functions of uncharacterized Znf proteins.

Functional volumes, niche packing and species richness: biogeographic legacies in the Congo Basin.

Understanding the determinants of species coexistence in complex and species-rich communities is a fundamental goal of ecology. Patterns of species coexistence depend on how biotic interactions and environmental filtering act over ecological and evolutionary time scales. Climatic fluctuations in lowland rainforests of the Congo Basin led to the number of vertebrate species being significantly lower in central compared with northern ecoregions of the Basin. We used null models to assess whether climatic variations affected the community assembly of shrews. A consistent limit to functional similarity of species was not related to species richness. Rather, species richness is constrained by environmental factors, and these constraints are stronger in the central lowland forests of the Congo Basin. By constraining species geographic distributions, historical effects of rainforest refugia arising from climatic fluctuations may affect contemporary species composition of local shrew communities. The Congo River represents a vicariance event that led to allopatric speciation of shrews and continues to represent a barrier to dispersal. Ultimately, the historical effects of this barrier have led to differences in the functional volume of shrew communities in northern and central ecoregions. We suggest that the analyses of community assembly can be used to identify Holocene refugia in the Congo Basin.

Mitochondrial impairment drives intestinal stem cell transition into dysfunctional Paneth cells predicting Crohn’s disease recurrence

ObjectiveReduced Paneth cell (PC) numbers are observed in inflammatory bowel diseases and impaired PC function contributes to the ileal pathogenesis of Crohn’s disease (CD). PCs reside in proximity to Lgr5+...

Short and simple sequences favored the emergence of N-helix phospho-ligand binding sites in the first enzymes

The ubiquity of phospho-ligands suggests that phosphate binding emerged at the earliest stage of protein evolution. To evaluate this hypothesis and unravel its details, we identified all phosphate-binding protein lineages in the Evolutionary Classification of Protein Domains database. We found at least 250 independent evolutionary lineages that bind small molecule cofactors and metabolites with phosphate moieties. For many lineages, phosphate binding emerged later as a niche functionality, but for the oldest protein lineages, phosphate binding was the founding function. Across some 4 billion y of protein evolution, side-chain binding, in which the phosphate moiety does not interact with the backbone at all, emerged most frequently. However, in the oldest lineages, and most characteristically in αβα sandwich enzyme domains, N-helix binding sites dominate, where the phosphate moiety sits atop the N terminus of an α-helix. This discrepancy is explained by the observation that N-helix binding is uniquely realized by short, contiguous sequences with reduced amino acid diversity, foremost Gly, Ser, and Thr. The latter two amino acids preferentially interact with both the backbone amide and the side-chain hydroxyl (bidentate interaction) to promote binding by short sequences. We conclude that the first αβα sandwich domains emerged from shorter and simpler polypeptides that bound phospho-ligands via N-helix sites.

Laminin is the ECM niche for trophoblast stem cells.

The niche is a specialized microenvironment for tissue stem cells in vivo. It has long been emphasized that niche ECM molecules act on tissue stem cells to regulate their behavior, but the molecular entities of these interactions remain to be fully elucidated. Here, we report that laminin forms the in vivo ECM niche for trophoblast stem cells (TSCs), the tissue stem cells of the placenta. TSCs expressed fibronectin-binding, vitronectin-binding, and laminin-binding integrins, whereas the integrin ligands present in the TSC niche were collagen and laminin. Therefore, the only niche integrin ligand available for TSCs in vivo was laminin. Laminin promoted TSC adhesion and proliferation in vitro in an integrin binding-dependent manner. Importantly, when the integrin-binding ability of laminin was genetically ablated in mice, the size of the TSC population was significantly reduced compared with that in control mice. The present findings underscore an ECM niche function of laminin to support tissue stem cell maintenance in vivo.

Trophic Selective Pressures Organize the Composition of Endolithic Microbial Communities From Global Deserts.

Studies of microbial biogeography are often convoluted by extremely high diversity and differences in microenvironmental factors such as pH and nutrient availability. Desert endolithic (inside rock) communities are relatively simple ecosystems that can serve as a tractable model for investigating long-range biogeographic effects on microbial communities. We conducted a comprehensive survey of endolithic sandstones using high-throughput marker gene sequencing to characterize global patterns of diversity in endolithic microbial communities. We also tested a range of abiotic variables in order to investigate the factors that drive community assembly at various trophic levels. Macroclimate was found to be the primary driver of endolithic community composition, with the most striking difference witnessed between hot and polar deserts. This difference was largely attributable to the specialization of prokaryotic and eukaryotic primary producers to different climate conditions. On a regional scale, microclimate and properties of the rock substrate were found to influence community assembly, although to a lesser degree than global hot versus polar conditions. We found new evidence that the factors driving endolithic community assembly differ between trophic levels. While phototrophic taxa, mostly oxygenic photosynthesizers, were rigorously selected for among different sites, heterotrophic taxa were more cosmopolitan, suggesting that stochasticity plays a larger role in heterotroph assembly. This study is the first to uncover the global drivers of desert endolithic diversity using high-throughput sequencing. We demonstrate that phototrophs and heterotrophs in the endolithic community assemble under different stochastic and deterministic influences, emphasizing the need for studies of microorganisms in context of their functional niche in the community.

BMP Antagonists Secreted by Mesenchymal Stromal Cells Improve Colonic Organoid Formation: Application for the Treatment of Radiation-induced Injury

Radiation therapy is crucial in the therapeutic arsenal to cure cancers; however, non-neoplastic tissues around an abdominopelvic tumor can be damaged by ionizing radiation. In particular, the radio-induced death of highly proliferative stem/progenitor cells of the colonic mucosa could induce severe ulcers. The importance of sequelae for patients with gastrointestinal complications after radiotherapy and the absence of satisfactory management has opened the field to the testing of innovative treatments. The aim of this study was to use adult epithelial cells from the colon, to reduce colonic injuries in an animal model reproducing radiation damage observed in patients. We demonstrated that transplanted in vitro-amplified epithelial cells from colonic organoids (ECO) of C57/Bl6 mice expressing green fluorescent protein implant, proliferate, and differentiate in irradiated mucosa and reduce ulcer size. To improve the therapeutic benefit of ECO-based treatment with clinical translatability, we performed co-injection of ECO with mesenchymal stromal cells (MSCs), cells involved in niche function and widely used in clinical trials. We observed in vivo an improvement of the therapeutic benefit and in vitro analysis highlighted that co-culture of MSCs with ECO increases the number, proliferation, and size of colonic organoids. We also demonstrated, using gene expression analysis and siRNA inhibition, the involvement of bone morphogenetic protein antagonists in MSC-induced organoid formation. This study provides evidence of the potential of ECO to limit late radiation effects on the colon and opens perspectives on combined strategies to improve their amplification abilities and therapeutic effects.