Nature Communications 2023

IFNg-Stat1 axis drives aging-associated loss of intestinal tissue homeostasis and regeneration

Omid Omrani, Anna Krepelova, Seyed Mohammad Mahdi Rasa, Dovydas Sirvinskas, Jing Lu, Francesco Annunziata, George Garside, Seerat Bajwa, Susanne Reinhardt, Lisa Adam, Sandra Käppel, Nadia Ducano, Daniela Donna, Alessandro Ori, Salvatore Oliviero, Karl Lenhard Rudolph & Francesco Neri

The influence of aging on intestinal stem cells (ISCs) and their niche can explain underlying causes for perturbation in ISC function observed during aging. However, molecular mechanisms for such a decrease in the functionality of ISCs during aging remain largely undetermined. Mechanistically, we identified increase in proinflammatory immune cells in the lamina propria of aged intestine as the main source of elevated interferon gamma (IFNg). Ifng-signaling leads to the induction of Stat1 activity in ISC priming them to aberrant differentiation and elevated antigen presentation in epithelial cells.
In-vivo inhibition of Ifng-signaling completely reverts these aging phenotypes and reinstalls regenerative capacity of the aged intestinal epithelium. Our findings disclose immune cell-mediated interferon signaling as a major driver of aging-related ISC priming that leads to skewed differentiation, autoantigen overexpression and loss of regenerative capacity of the aged intestinal epithelium.

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Journal of Biomedical Science 2022

Establishment and evaluation of module-based immune-associated gene signature to predict overall survival in patients of colon adenocarcinoma

Jing Lu, Francesco Annunziata, Dovydas Sirvinskas, Omid Omrani, Huahui Li, Seyed Mohammad Mahdi Rasa, Anna Krepelova, Lisa Adam & Francesco Neri

Patients with colon adenocarcinoma (COAD) exhibit significant heterogeneity in overall survival. The current tumor-node-metastasis staging system is insufficient to provide a precise prediction for prognosis.
We integrated different datasets and applied bioinformatic and statistical methods to construct a robust immune-associated risk model for COAD prognosis. The immune-associated risk model discriminated high-risk patients in our investigated and validated cohorts. Survival analyses demonstrated that our gene signature served as an independent risk factor for overall survival and the nomogram exhibited high accuracy. Functional analysis interpreted the correlation between our risk model and its role in prognosis by classifying groups with different immune activities. Remarkably, patients in the low-risk group showed higher immune activity, while those in the high-risk group displayed a lower immune activity.
Our study provides a novel tool that may contribute to the optimization of risk stratification for survival and personalized management of COAD.

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Cell Reports 2022

Inflammaging is driven by upregulation of innate immune receptors and systemic interferon signaling and is ameliorated by dietary restriction

Seyed Mohammad Mahdi Rasa, Francesco Annunziata, Anna Krepelova, Suneetha Nunna, Omid Omrani, Nadja Gebert, Lisa Adam, Sandra Käppel, Sven Höhn, Giacomo Donati, Tomasz Piotr Jurkowski, Karl Lenhard Rudolph, Alessandro Ori & Francesco Neri

Aging is characterized by a chronic low-grade inflammation known as inflammaging in multiple tissues, representing a risk factor for age-related diseases. Dietary restriction (DR) is the best-known non-invasive method to ameliorate aging in many organisms. However, the molecular mechanism and the signaling pathways that drive inflammaging across different tissues and how they are modulated by DR are not yet understood. Here we identify a multi-tissue gene network regulating inflammaging. This network is characterized by chromatin opening and upregulation in the transcription of innate immune system receptors and by activation of interferon signaling through interferon regulatory factors, inflammatory cytokines, and Stat1-mediated transcription. DR ameliorates aging-induced alterations of chromatin accessibility and RNA transcription of the inflammaging gene network while failing to rescue those alterations on the rest of the genome. Our results present a comprehensive understanding of the molecular network regulating inflammation in aging and DR and provide anti-inflammaging therapeutic targets.

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Nature Communications 2021

Establishment of a fluorescent reporter of RNA-polymerase II activity to identify dormant cells

Seyed Mohammad Mahdi Rasa, Francesco Annunziata, Anna Krepelova, Suneetha Nunna, Omid Omrani, Nadja Gebert, Lisa Adam, Sandra Käppel, Sven Höhn, Giacomo Donati, Tomasz Piotr Jurkowski, Karl Lenhard Rudolph, Alessandro Ori & Francesco Neri

Dormancy, a reversible quiescent cellular state characterized by greatly reduced metabolic activity, protects from genetic damage, prolongs survival and is crucial for tissue homeostasis and cellular response to injury or transplantation. Dormant cells have been characterized in many tissues, but their identification, isolation and characterization irrespective of tissue of origin remains elusive. Here, we develop a live cell ratiometric fluorescent Optical Stem Cell Activity Reporter (OSCAR) based on the observation that phosphorylation of RNA Polymerase II (RNApII), a hallmark of active mRNA transcription elongation, is largely absent in dormant stem cells from multiple lineages. 
Using the small intestinal crypt as a model, OSCAR reveals in real time the dynamics of dormancy induction and cellular differentiation in vitro, and allows the identification and isolation of several populations of transcriptionally diverse OSCARhigh and OSCARlow intestinal epithelial cell states in vivo. In particular, this reporter is able to identify a dormant OSCARhigh cell population in the small intestine. OSCAR therefore provides a tool for a better understanding of dormant stem cell biology.

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Molecular Cancer Therapeutics 2021

Characterization of Novel α-Mangostin and Paeonol Derivatives With Cancer-Selective Cytotoxicity

Suneetha Nunna, Ying-Pei Huang, Mahdi Rasa, Anna Krepelova, Francesco Annunziata, Lisa Adam, Sandra Käppel, Ming-Hua Hsu & Francesco Neri

α-Mangostin (aMan) and Paeonol (Pae) have shown anticancer and anti-inflammatory properties. However, these two natural compounds have no clinical value because of their low solubility and low membrane permeability. In this study, we screened chemically synthesized derivatives from these two natural compounds as potential novel chemicals that increase cancer cell cytotoxicity over nontransformed human cells. 
We found that two derivative compounds, named α-Mangostin-1 (aMan1) and Paeonol-1 (Pae1) more efficiently and more specifically induced cytotoxicity in HCT116, HT29, and SW48 colorectal cancer cell lines than the parental compounds. Both aMan1 and Pae1 arrested HCT116 cells in the G1 phase and HT29 and SW48 cells in the G2–M phase of the cell cycle. Both aMan1 and Pae1 induced apoptosis in human colorectal cancer cells, through a caspase-dependent mechanism. aMan1 and Pae1 induced selective transcriptional responses in colorectal cancer cells involving genes related to metabolic stress and DNA damage response signaling pathways. Finally, experiments on primary colon organoids showed that both derivatives were able to kill cancer-derived organoids without affecting the viability of organoids derived from healthy tissue, where the parental compounds and the currently used chemotherapeutic drug irinotecan failed. 
In conclusion, our findings expand the knowledge of natural compound derivatives as anticancer agents and open new avenues of research in the derivation of lead compounds aimed at developing novel chemotherapeutic drugs for colorectal cancer treatment that selectively target cancer, but not healthy cells.

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Scientific Reports 2020

Characterization of an in vitro 3D intestinal organoid model by using massive RNAseq-based transcriptome profiling

Jing Lu, Anna Krepelova, Seyed Mohammad Mahdi Rasa, Francesco Annunziata, Olena Husak, Lisa Adam, Suneetha Nunna & Francesco Neri

Organoids culture provides unique opportunities to study human diseases and to complement animal models. Several organs and tissues can be in vitro cultured in 3D structures resembling in vivo tissue organization. Organoids culture contains most of the cell types of the original tissue and are maintained by growth factors mimicking the in vivo state. However, the system is yet not fully understood, and specific in vivo features especially those driven by cell-extrinsic factors may be lost in culture. 
Here we show a comprehensive transcriptome-wide characterization of mouse gut organoids derived from different intestinal compartments and from mice of different gender and age. RNA-seq analysis showed that the in vitro culture strongly influences the global transcriptome of the intestinal epithelial cells (~ 60% of the total variance). Several compartment-, age- and gender-related transcriptome features are lost after culturing indicating that they are driven by niche or systemic factors. However, certain intrinsic transcriptional programs, for example, some compartment-related features and a minority of gender- and aging- related features are maintained in vitro which suggested possibilities for these features to be studied in this system. 
Moreover, our study provides knowledge about the cell-extrinsic or cell-intrinsic origin of intestinal epithelial transcriptional programs. We anticipated that our characterization of this in vitro system is an important reference for scientists and clinicians using intestinal organoids as a research model.

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 Mechanisms of Ageing and Development 2020

Intestinal stem cells heterogeneity and clonal dominance during aging: two faces of the same coin?

Dovydas Sirvinskas, Francesco Annunziata & Francesco Neri

Intestinal epithelium undergoes dysfunctions and diseases over time with an exponential increase in the elderly population. Recent studies reported that the intestinal stem cells (ISCs) show a functional decline during aging and a lack of an appropriate cell identity control. Increase of cell-to-cell heterogeneity is a hallmark of aging tissues and organs, however there is little experimental evidence with regard to the cell heterogeneity of the ISCs. On the other hand, the ISCs continuously experience a niche clonality process that diminishes the initial cell heterogeneity over time. 
In this article, we discuss the latest findings on these topics focusing on the potential mechanisms driving intestinal stem cell heterogeneity and clonality during aging.

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 Nature Reviews Molecular Cell Biology 2018

Cellular and epigenetic drivers of stem cell ageing

Maria Ermolaeva, Francesco Neri, Alessandro Ori & K. Lenhard Rudolph

Adult tissue stem cells have a pivotal role in tissue maintenance and regeneration throughout the lifespan of multicellular organisms. Loss of tissue homeostasis during post-reproductive lifespan is caused, at least in part, by a decline in stem cell function and is associated with an increased incidence of diseases. Hallmarks of ageing include the accumulation of molecular damage, failure of quality control systems, metabolic changes and alterations in epigenome stability. 
In this Review, we discuss recent evidence in support of a novel concept whereby cell-intrinsic damage that accumulates during ageing and cell-extrinsic changes in ageing stem cell niches and the blood result in modifications of the stem cell epigenome. These cumulative epigenetic alterations in stem cells might be the cause of the deregulation of developmental pathways seen during ageing. In turn, they could confer a selective advantage to mutant and epigenetically drifted stem cells with altered self-renewal and functions, which contribute to the development of ageing-associated organ dysfunction and disease.

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 Nature 2016

Intragenic DNA methylation prevents spurious transcription initiation

Francesco Neri, Stefania Rapelli, Anna Krepelova, Danny Incarnato, Caterina Parlato, Giulia Basile, Mara Maldotti, Francesca Anselmi & Salvatore Oliviero

In mammals, DNA methylation occurs mainly at CpG dinucleotides. Methylation of the promoter suppresses gene expression, but the functional role of gene-body DNA methylation in highly expressed genes has yet to be clarified. Here we show that, in mouse embryonic stem cells, Dnmt3b-dependent intragenic DNA methylation protects the gene body from spurious RNA polymerase II entry and cryptic transcription initiation. 
Using different genome-wide approaches, we demonstrate that this Dnmt3b function is dependent on its enzymatic activity and recruitment to the gene body by H3K36me3. Furthermore, the spurious transcripts can either be degraded by the RNA exosome complex or capped, polyadenylated, and delivered to the ribosome to produce aberrant proteins. Elongating RNA polymerase II therefore triggers an epigenetic crosstalk mechanism that involves SetD2, H3K36me3, Dnmt3b and DNA methylation to ensure the fidelity of gene transcription initiation, with implications for intragenic hypomethylation in cancer.

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A., Krepelova, F., Neri*. (2023). DNA methylation controls hematopoietic stem cell aging. Nat. Aging, 1–3.  (* Corresponding author).
S. Bonzano, E. Dallorto, I. Molineris, F. Michelon, I. Crisci, G. Gambarotta, F. Neri, S. Oliviero, R. Beckervordersandforth, D. C. Lie, P. Peretto, S. Bovetti, M. Studer, S. D. Marchis,. (2023). Nr2f1 shapes mitochondria in the mouse brain unraveling new insights into the neurodevelopmental disorder BBSOAS. Dis. Model. Mech. 16, dmm049854.

Omrani, O., Krepelova, A., Rasa, M., Syrvinskas, D., Lu, J., Annunziata, F., Garside, G., Bajwa, S., Reinhardt, S., Adam, L., Käppel, S., Ducano, N., Donna, D., Ori, A., Oliviero, S., Rudolph, K.L., Neri, F.* (2023). IFNg-Stat1 axis drives aging-associated loss of intestinal tissue homeostasis and regeneration. Nat Commun, 14, 6109. (* Corresponding author).


Lauria, A., Meng, G., Proserpio, V., Rapelli, S., Maldotti, M., Polignano, I.L., Anselmi, F., Incarnato, D., Krepelova, A., Donna, D., Levron, C.L., Donati, G., Molineris, I., Neri, F., and Oliviero, S. (2023). DNMT3B supports meso-endoderm differentiation from mouse embryonic stem cells. Nat Commun 14, 367.


 Annunziata, F., Rasa, S.M.M., Krepelova, A., Lu, J., Minetti, A., Omrani, O., Nunna, S., Adam, L., Käppel, S., and Neri, F.* (2022). Paneth Cells drive Intestinal Stem Cell Competition and Clonality in Aging and Calorie Restriction. Eur J Cell Biol 151282. (* Corresponding author).


Astanina, E., Doronzo, G., Corà, D., Neri, F., Oliviero, S., Genova, T., Mussano, F., Middonti, E., Vallariello, E., Cencioni, C., et al. (2022). The TFEB-TGIF1 axis regulates EMT in mouse epicardial cells. Nat Commun 13, 5191.


Azeez, H.J., Neri, F., Feizi, M.A.H., and Babaei, E. (2022). Transcriptome Profiling of HCT-116 Colorectal Cancer Cells with RNA Sequencing Reveals Novel Targets for Polyphenol Nano Curcumin. Molecules 27, 3470.


Ehsani, M., Bartsch, S., Rasa, S.M.M., Dittmann, J., Pungsrinont, T., Neubert, L., Huettner, S.S., Kotolloshi, R., Schindler, K., Ahmad, A., Mosig, A.S., Adam, L., Ori, A., Neri, F., Berndt, A., Grimm, M-O., Baniahmad, A. (2022). The natural compound atraric acid suppresses androgen-regulated neo-angiogenesis of castration-resistant prostate cancer through angiopoietin 2. Oncogene 41, 3263–3277.


Elia, I., Realini, G., Mauro, V.D., Borghi, S., Bottoni, L., Tornambè, S., Vitiello, L., Weiss, S.J., Chiariello, M., Tamburrini, A., Oliviero, S., Neri, F., Orlandini, M., Galvagni, F. (2022). SNAI1 is upregulated during muscle regeneration and represses FGF21 and ATF3 expression by directly binding their promoters. Faseb J 36, e22401.


Lang, X., Shen, L., Zhu, T., Zhao, W., Chen, Y., Zhu, C., Su, Q., Wang, C., Wang, Y., Neri, F., et al. (2022). Role of Age-Related Changes in DNA Methylation in the Disproportionate Susceptibility and Worse Outcomes of Sepsis in Older Adults. Frontiers Medicine 9, 822847.


Lu, J., Annunziata, F., Sirvinskas, D., Omrani, O., Li, H., Rasa, S.M.M., Krepelova, A., Adam, L., and Neri, F.* (2022). Establishment and evaluation of module-based immune-associated gene signature to predict overall survival in patients of colon adenocarcinoma. J Biomed Sci 29, 81. (* Corresponding author).


Rasa, S.M.M., Annunziata, F., Krepelova, A., Nunna, S., Omrani, O., Gebert, N., Adam, L., Käppel, S., Höhn, S., Donati, G., Jurkowsky, T.P., Rudolph, K.L., Ori, A., Neri, F.* (2022). Inflammaging is driven by upregulation of innate immune receptors and systemic interferon signaling and is ameliorated by dietary restriction. Cell Reports 39, 111017. (* Corresponding author).


Schomann, T., Mirzakhani, K., Kallenbach, J., Lu, J., Rasa, S.M.M., Neri, F., and Baniahmad, A. (2022). Androgen-Induced MIG6 Regulates Phosphorylation of Retinoblastoma Protein and AKT to Counteract Non-Genomic AR Signaling in Prostate Cancer Cells. Biomol 12, 1048.


Širvinskas, D., Omrani, O., Lu, J., Rasa, M., Krepelova, A., Adam, L., Kaeppel, S., Sommer, F., and Neri, F. (2022). Single-cell atlas of the aging mouse colon. Iscience 25, 104202. (* Corresponding author).


Lang, X., Shen, L., Zhu, T., Zhao, W., Chen, Y., Zhu, C., Su, Q., Wang, C., Wang, Y., Neri, F., et al. (2022). Role of Age-Related Changes in DNA Methylation in the Disproportionate Susceptibility and Worse Outcomes of Sepsis in Older Adults. Frontiers Medicine 9, 822847.



Melekhova, A., Leeder, M., Pungsrinont, T., Schmäche, T., Kallenbach, J., Ehsani, M., Mirzakhani, K., Rasa, S.M.M., Neri, F., and Baniahmad, A. (2021). A Novel Splice Variant of the Inhibitor of Growth 3 Lacks the Plant Homeodomain and Regulates Epithelial–Mesenchymal Transition in Prostate Cancer Cells. Biomol 11, 1152.


Mirzakhani, K., Kallenbach, J., Rasa, S.M.M., Ribaudo, F., Ungelenk, M., Ehsani, M., Gong, W., Gassler, N., Leeder, M., Grimm, M.-O., Neri, F., et al. (2021). The androgen receptor—lncRNASAT1-AKT-p15 axis mediates androgen-induced cellular senescence in prostate cancer cells. Oncogene 41 (7), 943-959.


Nunna, S., Huang, Y.-P., Rasa, M., Krepelova, A., Annunziata, F., Adam, L., Käppel, S., Hsu, M.-H., and Neri, F.* (2021). Characterization of novel alpha-Mangostin and Paeonol derivatives with cancer-selective cytotoxicity. Mol Cancer Ther 21, (2), 257-270. (* Corresponding author)


Ebrahimi, M., Babaei, E., Neri, F., and Feizi, M.A.H. (2021). Anti-proliferative and apoptotic effect of gemini curcumin in p53-wild type and p53-mutant colorectal cancer cell lines. Int J Pharmaceut 601, 120592.


Bartsch, S., Mirzakhani, K., Neubert, L., Stenzel, A., Ehsani, M., Esmaeili, M., Pungsrinont, T., Kacal, M., Rasa, S.M.M., Kallenbach, J., Damodaran, D., Ribaudo, F., Grimm, M.O., Neri, F., and Baniahmad, A.. (2021). Antithetic hTERT Regulation by Androgens in Prostate Cancer Cells: hTERT Inhibition Is Mediated by the ING1 and ING2 Tumor Suppressors. Cancers 13, 4025.


Krepelova, A., and Neri, F.* (2021). Enhancers and Promoters, Methods and Protocols: Low-Input Whole-Genome Bisulfite Sequencing. Methods Mol Biology 2351, 353–368. (* Corresponding author).


Freter, R., Falletta, P., Omrani, O., Rasa, M., Herbert, K., Annunziata, F., Minetti, A., Krepelova, A., Adam, L., Käppel, S., Rüdiger, T., Wang, ZQ., Goding, C.*, and Neri, F.* (2021). Establishment of a fluorescent reporter of RNA-polymerase II activity to identify dormant cells. Nature Communications 12, 3318–16. (* Corresponding authors).


Dabaghi, M., Rasa, S.M.M., Cirri, E., Ori, A., Neri, F., Quaas, R., and Hilger, I. (2021). Iron Oxide Nanoparticles Carrying 5-Fluorouracil in Combination with Magnetic Hyperthermia Induce Thrombogenic Collagen Fibers, Cellular Stress, and Immune Responses in Heterotopic Human Colon Cancer in Mice. Pharmaceutics 2021, 13 (10), 1625. 


Marx, C., Sonnemann, J., Beyer, M., Maddocks, O.D.K., Lilla, S., Hauzenberger, I., Piée‐Staffa, A., Siniuk, K., Nunna, S., ..., Neri, F., Heinzel, T., Wang ZQ., and Kramer, O. (2021). Mechanistic insights into p53‐regulated cytotoxicity of combined entinostat and irinotecan against colorectal cancer cells. Mol Oncol. 15 (12), 3404-3429.


Tapias, A., Lázaro, D., Yin, B.-K., Rasa, S. M. M., Krepelova, A., Kelmer Sacramento, E., Grigaravicius, P., Koch, P., Kirkpatrick, J., Ori, A., Neri, F., Wang ZQ. (2021). HAT cofactor TRRAP modulates microtubule dynamics via SP1 signaling to prevent neurodegeneration. eLife, 10.


 Sirvinskas, D., Annunziata, F., & Neri, F.* (2020). Intestinal stem cells heterogeneity and clonal dominance during aging: two faces of the same coin? Mechanisms of Ageing and Development, 189, 111247. (* Corresponding author).


Zhu, C., Xiang, W., Li, B., Wang, Y., Feng, S., Wang, C., … , Neri, F et al. (2020). DNA methylation modulates allograft survival and acute rejection after renal transplantation by regulating the mTOR pathway. American Journal of Transplantation, ajt.16183.

Lu, J., Krepelova, A., Rasa, S.M.M., Annunziata, F., Husak, O., Adam, L., Nunna, S., and Neri, F.* (2020). Characterization of an in vitro 3D intestinal organoid model by using massive RNAseq-based transcriptome profiling. Scientific Reports -Uk 11 (1), 1-14. (* Corresponding author).

Bertacchi, M., Romano, A. L., Loubat, A., Tran Mau Them, F., Willems, M., Faivre, L., … , Neri, F et al. (2020). NR2F1 regulates regional progenitor dynamics in the mouse neocortex and cortical gyrification in BBSOAS patients. The EMBO Journal, 39(13), e104163.



Cencioni, C., Heid, J., Krepelova, A., Rasa, S. M. M., Kuenne, C., Guenther, S., … , Neri, F et al. (2019). Aging Triggers H3K27 Trimethylation Hoarding in the Chromatin of Nothobranchius furzeri Skeletal Muscle. Cells, 8(10).


Chen, Z., Amro, E. M., Becker, F., Hölzer, M., Rasa, S. M. M., Njeru, S. N., … , Neri, F et al. (2019). Cohesin-mediated NF-κB signaling limits hematopoietic stem cell self-renewal in aging and inflammation. The Journal of Experimental Medicine, 216(1), 152–175.


Ermolaeva M. *, Neri F. *, Ori A. *, Rudolph K.L. * (2018). Cellular and epigenetic drivers of stem cell ageing. Nature Reviews Molecular Cell Biology, 20(Suppl. 1), 667.  (* Corresponding authors).


Doronzo, G., Astanina, E., Corà, D., Chiabotto, G., Comunanza, V., Noghero, A., Neri, F et al. (2018). TFEB controls vascular development by regulating the proliferation of endothelial cells. The EMBO Journal.


Grassi, E., Santoro, R., Umbach, A., Grosso, A., Oliviero, S., Neri, F., et al. (2018). Choice of Alternative Polyadenylation Sites, Mediated by the RNA-Binding Protein Elavl3, Plays a Role in Differentiation of Inhibitory Neuronal Progenitors. Frontiers in Cellular Neuroscience, 12, 235.


Bruno, S., Tapparo, M., Collino, F., Chiabotto, G., Deregibus, M. C., Soares Lindoso, R., Neri, F.,  et al. (2017). Renal Regenerative Potential of Different Extracellular Vesicle Populations Derived from Bone Marrow Mesenchymal Stromal Cells. Tissue Engineering Part A, ten.tea.2017.0069. 


Neri, F.*, Rapelli, S., Krepelova, A., Incarnato, D., Maldotti, M., Parlato, C., Anselmi F., Basile G., and Oliviero, S.* (2017). Intragenic DNA methylation prevents spurious transcription initiation. Nature, 543(7643), 72–77. (* Corresponding authors). 

Highlighted on: Research, A. A. F. C. (2017). DNMT3B-Mediated Gene Body Methylation Suppresses Aberrant Transcription. Cancer Discovery.

Highlighted on: Zlotorynski, E. (2017). Epigenetics: DNA methylation prevents intragenic transcription. Nature Reviews Molecular Cell Biology, 18(4), 212–213.

Highlighted on: Teissandier, A., & Bourc'his, D. (2017). Gene body DNA methylation conspires with H3K36me3 to preclude aberrant transcription. The EMBO Journal, e201796812.


Audrito, V., Serra, S., Stingi, A., Orso, F., Gaudino, F., Bologna, C., Neri, F.,  et al. (2017). PD-L1 up-regulation in melanoma increases disease aggressiveness and is mediated through miR-17-5p. Oncotarget, 5(0). 


Bianchi, F.T., Tocco C., Pallavicini, G., Liu Y., Vernì F.,, … Neri, F., Oliviero, S., Mauro,A., Geley, S., Gatti, M., and Di Cunto, F. (2017). Citron Kinase deficiency leads to chromosomal instability and TP53-sensitive microcephaly. Cell Reports, 18(7), 1674–1686.. 


Tassone, B., Saoncella, S., Neri, F., et al. (2017). Rictor/mTORC2 deficiency enhances keratinocyte stress tolerance via mitohormesis. Cell Death and Differentiation, 


Arruga, F., Gizdic, B., Bologna, C., Cignetto, S., Buonincontri, R., Serra, S., Vaisitti, T., Gizzi, K., Vitale, N., Garaffo, G., Mereu, E., Diop, F., Neri, F., et al. (2016). Mutations in NOTCH1 PEST-domain orchestrate CCL19-driven homing of Chronic Lymphocytic Leukemia cells by modulating the tumor suppressor gene DUSP22. Leukemia. 


Schwörer, S.,  Becker, F., Feller, C., . . . . . . ,  Kestler, H.A., Neri F.,  von Maltzahn, J.,  Tümpel, S., and Rudolph, K.L. (2016). Epigenetic stress responses induce muscle stem-cell ageing by Hoxa9 developmental signals. Nature, 540(7633), 428–432. 


Incarnato, D., Anselmi, F., Morandi, E., Neri, F., Maldotti, M., Rapelli, S., et al. (2017). High-throughput single-base resolution mapping of RNA 2'-O-methylated residues. Nucleic Acids Research, 45(3), 1433–1441.. 


Neri, F., Incarnato, D., Krepelova, A., Parlato, C., and Oliviero, S. (2016). Methylation-assisted bisulfite sequencing to simultaneously map 5fC and 5caC on a genome-wide scale for DNA demethylation analysis. Nature Protocols, 11(7), 1191–1205. 


Maldotti, M., Incarnato, D., Neri, F., Krepelova, A., Rapelli, S., Anselmi, F., et al. (2016). The long intergenic non-coding RNA CCR492 functions as a let-7 competitive endogenous RNA to regulate c-Myc expression. Biochimica Et Biophysica Acta, 1859(10), 1322–1332. 



Incarnato, D., Neri, F., Anselmi, F., and Oliviero, S. (2015). RNA structure framework: automated transcriptome-wide reconstruction of RNA secondary structures from high-throughput structure probing data. Bioinformatics btv571. 


Neri, F.,  Incarnato, D., Krepelova, A., Dettori, D., Rapelli, S., Maldotti, M., Parlato, C., Anselmi, F., Galvagni, F., and Oliviero, S. (2015).  TET1 is controlled by pluripotency-associated factors in ESCs and downmodulated by PRC2 in differentiated cells and tissues. Nucleic Acids Research. 43, 6814–6826. 


Neri, F., Incarnato, D., Krepelova, A., Rapelli, S., Parlato, C., and Oliviero, S. (2015). Single base resolution analysis of 5-formyl and 5-carboxyl cytosine reveals the promoter DNA methylation dynamics. CellReports, 10(5), 674–683. 


Collino F., Bruno S., Incarnato D., Dettori D., Neri F., Oliviero S., Tetta C., Quesenberry P., and Camussi G. (2015). AKI Recovery Induced by Mesenchymal Stromal Cell-Derived Extracellular Vesicles Carrying MicroRNAs. Journal of the American Society of Nephrology.JASN, ASN.2014070710.  


Galvagni, F.*, Lentucci, C.*, Neri, F*., Dettori, D., DeClemente, C., Orlandini, M., Anselmi, F., Rapelli, S., Grillo, M., Borghi, S., et al. (2014). Snai1 promotes ESC exit from the pluripotency by direct repression of self-renewal genes. Stem Cells 33, 742–750. (*co-first author)


Incarnato, D., Neri, F.,  Anselmi, F., and Oliviero, S. (2014). Genome-wide profiling of mouse RNA secondary structures reveals key features of the mammalian transcriptome. Genome Biology 15, 491. 


Neri, F., Dettori, D., Incarnato, D., Krepelova, A., Rapelli, S., Maldotti, M., Parlato, C., Panagiotis, P., and Oliviero, S. (2014). TET1 is a tumour suppressor that inhibits colon cancer growth by derepressing inhibitors of the WNT pathway. Oncogene 34, 4168–4176. 


Incarnato, D., Krepelova, A., and Neri, F* (2014). High-throughput single nucleotide variant discovery in E14 mouse embryonic stem cells provides a new reference genome assembly. Genomics 104, 121–127.(*corresponding author).


Fiorito, V., Neri, F., Pala, V., Silengo, L., Oliviero, S., Altruda, F., and Tolosano, E. (2014). Hypoxia controls Flvcr1 gene expression in Caco2 cells through HIF2α and ETS1. Biochim. Biophys. Acta 1839, 259–264. 


Krepelova, A.*, Neri, F.*, Maldotti, M., Rapelli, S., and Oliviero, S. (2014). Myc and Max genome-wide binding sites analysis links the Myc regulatory network with the Polycomb and the Core pluripotency networks in mouse embryonic stem cells. Plos One 9, e88933. (*co-first author)


Neri, F., Krepelova, A., Incarnato, D., Maldotti, M., Parlato, C., Galvagni, F., Matarese, F., Stunnenberg, H.G., and Oliviero, S. (2013). Dnmt3L Antagonizes DNA Methylation at Bivalent Promoters and Favors DNA Methylation at Gene Bodies in ESCs. Cell 155, 121–134. 


Neri, F., Incarnato, D., Krepelova, A., Rapelli, S., Pagnani, A., Zecchina, R., Parlato, C., and Oliviero, S. (2013). Genome-wide analysis identifies a functional association of Tet1 and Polycomb repressive complex 2 in mouse embryonic stem cells. Genome Biology 14, R91. 


Incarnato, D., Neri, F., Diamanti, D., and Oliviero, S. (2013). MREdictor: a two-step dynamic interaction model that accounts for mRNA accessibility and Pumilio binding accurately predicts microRNA targets. Nucleic Acids Research 41, 8421–8433. 


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