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Patients with COVID-19 may develop abnormal inflammatory response and lymphopenia, followed in some cases by delayed-onset syndromes, often long-lasting after the initial SARS-CoV-2 infection. As viral infections may activate human endogenous retroviral elements (HERV), we studied the effect of SARS-CoV-2 on HERV-W and HERV-K envelope (ENV) expression, known to be involved in immunological and neurological pathogenesis of human diseases. Our results have showed that the exposure to SARS-CoV-2 virus activates early HERV-W and K transcription but only HERV-W ENV protein expression, in an infection- and ACE2-independent way within peripheral blood mononuclear cell cultures from one-third of healthy donors. Moreover, HERV-W ENV protein was significantly increased in serum and plasma of COVID-19 patients, correlating with its expression in CD3+ lymphocytes and with disease severity. Finally, HERV-W ENV was found expressed in post-mortem tissues of lungs, heart, brain olfactory bulb and nasal mucosa from acute COVID-19 patients in cell-types relevant for COVID-19-associated pathogenesis within affected organs, but different from those expressing of SARS-CoV-2 antigens. Altogether, the present study revealed that SARS-CoV-2 can induce HERV-W ENV expression in cells from individuals with symptomatic and severe COVID-19. Our data suggest that HERV-W ENV is likely to be involved in pathogenic features underlying symptoms of acute and post-acute COVID. It highlights the importance to further understand patients’ genetic susceptibility to HERV-W activation and the relevance of this pathogenic element as a prognostic marker and a therapeutic target in COVID-19 associated syndromes.Graphical abstract

23 pags., 11 figs., 14 tabs., A small-scale ITC benchmarking study was performed involving 9 biophysics laboratories/facilities, to evaluate inter-laboratory and intra-laboratory basal levels of uncertainty. Our prime goal was to assess a number of important factors that can influence both the data gathered by this technique and the thermodynamic parameter values derived therefrom. In its first part, the study involved 5 laboratories and 13 different instruments, working with centrally prepared samples and the same experimental protocol. The second part involved 4 additional laboratories and 6 more instruments, where the users prepared their own samples according to provided instructions and did the experiments following the same protocol as in the first part. The study design comprised: (1) selecting a minimal set of laboratories; (2) providing very stable samples; (3) providing samples not requiring preparation or manipulation; and (4) providing a well-defined and detailed experimental protocol. Thus, we were able to assess: (i) the variability due to instrument and data analysis performed by each user on centrally prepared samples; (ii) the comparability of data retrieved when using 4 different software packages to analyze the same data, besides the data analysis carried out by the different users on their own experimental results; and (iii) the variability due to local sample preparation (second part of the study). Individual values, as well as averages and standard deviations for the binding parameters for EDTA-cation interaction, were used as metrics for comparing the equilibrium association constant (logK), enthalpy of interaction (ΔH), and the so-called “stoichiometry” (n), a concentration-correction factor., M.B. acknowledges the fnancial support from Fundação para a Ciência e Tecnologia (FCT), Portugal, together with FEDER through “Programa Operacional Competitividade e Internacionalização” (POCI), by COMPETE2020 to Projects POCI-01-0145- FEDER-030579 and UIDB/00081/2020. A.V.C. and O.A. acknowledge fnancial support from the Spanish Ministry of Economy and Competitiveness and European ERDF Funds (MCIU/AEI/FEDER, EU) (BFU2013-47064-P and BFU2016-78232-P to A.V.C.), the Spanish Ministry of Education and Culture (FPU13/3870 to R.C.G.), Fondo de Investigaciones Sanitarias from Instituto de Salud Carlos III and European Union (ERDF/ESF, “Investing in your future”) (PI15/00663 and PI18/00349 to O.A.), Diputación General de Aragón (Protein Targets and Bioactive Compounds Group E45_20R to A.V.C. and Digestive Pathology Group B25_20R to O.A.) and Centro de Investigación Biomédica en Red en Enfermedades Hepáticas y Digestivas (CIBERehd). JBC was supported by NIH Grant GM077422. This work was supported by the Intramural Research Program of the National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health. MB gratefully acknowledges the support of Frederico Silva of the Biochemical and Biophysical Technologies Scientifc Platform of the Instituto de Investigação e Inovação em Saúde, I3S, Universidade do Porto. We all thank COST Action CA15126, Working Group 4, for the support to this study

Recent studies have identified strong relationships between delayed recovery of tree growth after drought and tree mortality caused by subsequent droughts. These observations raise concerns about forest ecosystem services and post-drought growth recovery given the projected increase in drought frequency and extremes. For quantifying the impact of extreme droughts on tree radial growth, we used a network of tree-ring width data of 1689 trees from 100 sites representing most of the distribution of two drought tolerant, deciduous oak species (Quercus petraea and Quercus robur). We first examined which climatic factors and seasons control growth of the two species and if there is any latitudinal, longitudinal or elevational trend. We then quantified the relative departure from pre-drought growth during droughts, and how fast trees were able to recover the pre-drought growth level. Our results showed that growth was more related to precipitation and climatic water balance (precipitation minus potential evapotranspiration) than to temperature. However, we did not detect any clear latitudinal, longitudinal or elevational trends except a decreasing influence of summer water balance on growth of Q. petraea with latitude. Neither species was able to maintain the pre-drought growth level during droughts. However, both species showed rapid recovery or even growth compensation after summer droughts but displayed slow recovery in response to spring droughts where none of the two species was able to fully recover the pre-drought growth-level over the three post-drought years. Collectively, our results indicate that oaks which are considered resilient to extreme droughts have also shown vulnerability when droughts occurred in spring especially at sites where long-term growth is not significantly correlated with climatic factors. This improved understanding of the role of drought seasonality and climate sensitivity of sites is key to better predict trajectories of post-drought growth recovery in response to the drier climate projected for Europe., Science of The Total Environment, 784, ISSN:0048-9697, ISSN:1879-1026

Background Human tuberculosis (TB) is caused by a plethora of Mycobacterium tuberculosis complex (MTBC) strains belonging to seven phylogenetic branches. Lineages 2, 3 and 4 are considered “modern” branches of the MTBC responsible for the majority of worldwide TB. Since the current BCG vaccine confers variable protection against pulmonary TB, new candidates are investigated. MTBVAC is the unique live attenuated vaccine based on M. tuberculosis in human clinical trials. Methods MTBVAC was originally constructed by unmarked phoP and fadD26 deletions in a clinical isolate belonging to L4. Here we construct new vaccines based on isogenic gene deletions in clinical isolates of the L2 and L3 modern lineages. These three vaccine candidates were characterized at molecular level and also in animal experiments of protection and safety. Findings Safety studies in immunocompromised mice showed that MTBVAC-L2 was less attenuated than BCG Pasteur, while the original MTBVAC was found even more attenuated than BCG and MTBVAC-L3 showed an intermediate phenotype. The three MTBVAC candidates showed similar or superior protection compared to BCG in immunocompetent mice vaccinated with each MTBVAC candidate and challenged with three representative strains of the modern lineages. Interpretation MTBVAC vaccines, based on double phoP and fadD26 deletions, protect against TB independently of the phylogenetic linage used as template strain for their construction. Nevertheless, lineage L4 confers the best safety profile. Funding European Commission (TBVAC2020, H2020-PHC-643381), Spanish Ministry of Science (RTI2018-097625-B-I00), Instituto de Salud Carlos III (PI18/0336), Gobierno de Aragón/Fondo Social Europeo and the French National Research Council (ANR-10-LABX-62-IBEID, ANR-16-CE35-0009, ANR-16-CE15-0003)., Graphical abstract Image, graphical abstract

Purpose: Treatment regimens using anti-vascular endothelial growth factor (anti-VEGF) therapy for neovascular age-related macular degeneration (nAMD) generally aim to dry the neovascular lesion, however recent evidence suggests that some fluid, particularly subretinal fluid (SRFL), may be tolerated. We assessed the relationship between fluid and visual outcomes using real-world data to test this hypothesis. Methods: Treatment-naïve eyes in the Fight Retinal Blindness! registry treated for nAMD from 1st January 2010 to 1st June 2018 were identified. Lesion activity was graded by practitioners as inactive, active (more than SRFL [i.e. had intraretinal fluid]) or active (SRFL only). Eyes were grouped based on their initial activity and their predominant activity status during the 12 months of follow-up. The primary outcome was the 12-month mean change in visual acuity (VA) between lesion activity subgroups. Results: There were 555 eyes eligible for the analysis. Visual outcomes between eyes that were initially active (any fluid) and initially active (SRFL only) were similar (P = 0.233), with slightly higher gains (mean [95% CI]) observed in initially active (more than SRFL only) eyes after multivariable adjustment (5.9 [4.4, 7.4] vs. 5.0 [2.3, 7.7] letters). However, mean baseline and final VA were worse in eyes that were initially active with more than SRFL only than in eyes with SRFL only (56.0 vs. 63.6 letters at baseline; P < 0.001 and 61.7 vs. 67.5 letters at 12 months; P = 0.002). There was a significant difference in visual outcomes over 12 months between the 3 predominant activity groups (P = 0.010). Predominantly inactive eyes gained the most mean (95% CI) VA at 12 months (7.2 [4.8, 9.6] letters), followed by predominantly SRFL only (7.0 [2.3, 4.7] letters), with predominantly any fluid eyes performing the worst (3.6 [2.1, 5.6] letters) after multivariable adjustment (Figure 1). Conclusions: Eyes that were predominantly active with more than SRFL only had worse outcomes than eyes that were predominantly inactive or active with SRFL only. The presence of SRFL did not appear to have a detrimental effect on 12-month outcomes.

Background: NUPR1 is a multifunctional intrinsically disordered protein (IDP) involved, among other functions, in chromatin remodelling, and development of pancreatic ductal adenocarcinoma (PDAC). It interacts with several biomolecules through hydrophobic patches around residues Ala33 and Thr68. The drug trifluoperazine (TFP), which hampers PDAC development in xenografted mice, also binds to those regions. Because of the large size of the hot-spot interface of NUPR1, small molecules could not be adequate to modulate its functions. Methods: We explored how amphipathic helical-designed peptides were capable of interacting with wild-type NUPR1 and the Thr68Gln mutant, inhibiting the interaction with NUPR1 protein partners. We used in vitro biophysical techniques (fluorescence, circular dichroism (CD), nuclear magnetic resonance (NMR) and isothermal titration calorimetry (ITC)), in silico studies (docking and molecular dynamics (MD)), and in cellulo protein ligation assays (PLAs) to study the interaction. Results: Peptide dissociation constants towards wild-type NUPR1 were ~ 3 μM, whereas no interaction was observed with the Thr68Gln mutant. Peptides interacted with wild-type NUPR1 residues around Ala33 and residues at the C terminus, as shown by NMR. The computational results clarified the main determinants of the interactions, providing a mechanism for the ligand-capture that explains why peptide binding was not observed for Thr68Gln mutant. Finally, the in cellulo assays indicated that two out of four peptides inhibited the interaction of NUPR1 with the C-terminal region of the Polycomb RING protein 1 (C-RING1B). Conclusions: Designed peptides can be used as lead compounds to inhibit NUPR1 interactions. General significance: Peptides may be exploited as drugs to target IDPs.

Biomonitoring is a research topic that has largely relied on cell culture systems. Recently, the development of “Organ-on-a-Chip” (OC) platforms and the need for a continuous monitoring of these systems has increased its interest. However, the biomonitorization in these systems is still at its infancy due to the difficulty to adapt the sensors to microfluidic OC systems. In this work we have fabricated a modular, versatile, scalable, multi-analyte sensing platform, which integrates dissolved oxygen (DO), Na, K and pH sensors for monitoring their concentrations in small volume of biological fluids. The platform is fabricated by means of rapid prototyping techniques using polymeric substrates, and incorporates all the necessary elements to measure the four analytes. It was designed with four gold sensing electrodes, and integrates a gold counter electrode and an Ag/AgCl pseudo-reference electrode for the electrochemical measurements in small volumes (0.83 μL) of samples. The sensors featured good sensitivities of 3.60 ± 0.2 nA (mg L) for DO and 69 ± 1 mV decade for pH. Na and K μISE exhibited sensitivities of 57 ± 1 mV decade and 52 ± 2 mV decade, and low limits of detection 5 × 10 M and 0.5 × 10 M respectively. This platform allows the dynamic measurement of the biological fluids parameters simultaneously, in real time and with a rapid response. The versatility of the platform allows its adaptation in any microfluidic cells culture systems. The novel multi-sensor platform has been validated in controlled buffers and with artificial urine (AU). A proof-of-concept using real mice urine (RU) has been carried out, demonstrating the good behaviour of the multi-sensing platform.

Although the incidence of tuberculosis (TB) is gradually decreasing in Spain, there is an increase in the proportion of foreign-born cases. This changing scenario is slowly shifting the local TB epidemiology from endemic to imported cases with an increased risk for multidrug-resistant (MDR) and extensively drug resistant (XDR) strains of Mycobacterium tuberculosis complex. MDR/XDR strains from Spain (n = 366 MTBC isolates, 1 strain per patient) isolated between 1998 and 2005 were retained for this retrospective analysis. All strains were analyzed by spoligotyping, while 12-loci MIRU-VNTR data were available for 106 isolates from 2003 to 2005. Demographic, phylogenetic, and epidemiologic analyses using anonymized data were collected and analyzed using the SITVIT2 database. Our study provides with a first snapshot of genetic diversity of MDR/XDR-TB in several autonomous regions of Spain. It highlights significantly more of SIT1/Beijing and SIT66/BOV MDR isolates (5.7% and 7.38% respectively) and increasingly more foreign-born cases from Eastern Europe. Future studies should focus on shared genotypes between Spanish and foreign-born patients to decipher the modes of transmission and risk factors involved, and decipher the proportion of imported cases of active disease versus cases of reactivation of latent TB infection among foreign-born individuals.

Intrinsically disordered proteins (IDPs) are prevalent in eukaryotes, performing signaling and regulatory functions. Often associated with human diseases, they constitute drug-development targets. NUPR1 is a multifunctional IDP, over-expressed and involved in pancreatic ductal adenocarcinoma (PDAC) development. By screening 1120 FDA-approved compounds, fifteen candidates were selected, and their interactions with NUPR1 were characterized by experimental and simulation techniques. The protein remained disordered upon binding to all fifteen candidates. These compounds were tested in PDAC-derived cell-based assays, and all induced cell-growth arrest and senescence, reduced cell migration, and decreased chemoresistance, mimicking NUPR1-deficiency. The most effective compound completely arrested tumor development in vivo on xenografted PDAC-derived cells in mice. Besides reporting the discovery of a compound targeting an intact IDP and specifically active against PDAC, our study proves the possibility to target the 'fuzzy' interface of a protein that remains disordered upon binding to its natural biological partners or to selected drugs.

International audience; Piceatannol is a hydroxylated derivative of resveratrol. While both dietary polyphenols coexist in edible plants and fruits, and share equivalent concentrations in several wines, the influence of piceatannol on adiposity has been less studied than that of resveratrol. Though resveratrol is now recognized to limit fat deposition in various obesity models, the benefit of its dietary supplementation remains under debate regarding human obesity treatment or prevention. The research for more potent resveratrol analogs is therefore still undergoing. This prompted us to compare various effects of piceatannol and resveratrol directly on human adipose tissue (hAT). Hydrogen peroxide release was measured by Amplex Red-based fluorescence in subcutaneous hAT samples from obese patients. Interactions of stilbenes with human amine oxidases and quinone reductase were assessed by radiometric methods, computational docking and electron paramagnetic resonance. Influences on lipogenic and lipolytic activities were compared in mouse adipocytes. Resveratrol and piceatannol inhibited monoamine oxidase (MAO) with respective IC50 of 18.5 and 133.7 μM, but not semicarbazide-sensitive amine oxidase (SSAO) in hAT. For both stilbenes, the docking scores were better for MAO than for SSAO. Piceatannol and resveratrol similarly hampered hydrogen peroxide detection in assays with and without hAT, while they shared pro-oxidant activities when incubated with purified quinone reductase. They exhibited similar dose-dependent inhibition of adipocyte lipogenic activity. Only piceatannol inhibited basal and stimulated lipolysis when incubated at a dose ≥100 μM. Thus, piceatannol exerted on fat cells dose-dependent effects similar to those of resveratrol, except for a stronger antilipolytic action. In this regard, piceatannol should be useful in limiting the lipotoxicity related to obesity when ingested or administered alone - or might hamper the fat mobilization induced by resveratrol when simultaneously administered with it.

Reprogramming of X-chromosome inactivation during the acquisition of pluripotency is accompanied by repression of Xist, the trigger of X-inactivation, and by upregulation of its antisense counterpart Tsix, which triggers resetting of the Xist locus. In undifferentiated embryonic stem cells, key transcription factors that support pluripotency — Nanog, Oct4 and Sox2 — repress Xist transcription. Here, upregulation of Tsix in embryonic stem cells is shown to depend on a different subset of pluripotency factors — Rex1, Klf4 and c-Myc. Therefore, two distinct embryonic-stem-cell-specific complexes couple reprogramming of X-inactivation to pluripotency. Reprogramming of X-chromosome inactivation during the acquisition of pluripotency is accompanied by repression of Xist, the trigger of X-inactivation, and by upregulation of its antisense counterpart, Tsix. In undifferentiated embryonic stem cells (ESCs), key transcription factors that support pluripotency repress Xist transcription. These authors show that upregulation of Tsix in ESCs depends on a different subset of pluripotency factors. Therefore, two distinct ESC-specific complexes couple reprogramming of X-inactivation to pluripotency. The reprogramming of X-chromosome inactivation during the acquisition of pluripotency in vivo and in vitro1 is accompanied by the repression of Xist2, the trigger of X-inactivation3, and the upregulation of its antisense counterpart Tsix4. We have shown that key factors supporting pluripotency—Nanog, Oct4 and Sox2—bind within Xist intron 1 in undifferentiated embryonic stem cells (ESC) to repress Xist transcription5. However, the relationship between transcription factors of the pluripotency network and Tsix regulation has remained unclear5,6. Here we show that Tsix upregulation in embryonic stem cells depends on the recruitment of the pluripotent marker Rex1, and of the reprogramming-associated factors Klf4 and c-Myc, by the DXPas34 minisatellite associated with the Tsix promoter. Upon deletion of DXPas34, binding of the three factors is abrogated and the transcriptional machinery is no longer efficiently recruited to the Tsix promoter. Additional analyses including knockdown experiments further demonstrate that Rex1 is critically important for efficient transcription elongation of Tsix. Hence, distinct embryonic-stem-cell-specific complexes couple X-inactivation reprogramming and pluripotency, with Nanog, Oct4 and Sox2 repressing Xist to facilitate the reactivation of the inactive X, and Klf4, c-Myc and Rex1 activating Tsix to remodel Xist chromatin7,8,9,10 and ensure random X-inactivation upon differentiation1. The holistic pattern of Xist/Tsix regulation by pluripotent factors that we have identified suggests a general direct governance of complex epigenetic processes by the machinery dedicated to pluripotency.

International audience; Resveratrol is beneficial in obese and diabetic rodents. However, its low bioavailability raises questions about its therapeutic relevance for treating or preventing obesity complications. In this context, many related natural polyphenols are being tested for their putative antidiabetic and anti-obesity effects. This prompted us to study the influence of piceatannol, a polyhydroxylated stilbene, on the prevention of obesity complications in Zucker obese rats. A 6-week supplementation was followed by the determination of various markers in plasma, liver, adipose tissue and heart, together with a large-scale analysis of gut microbiota composition. When given in doses of 15 or 45 mg/kg body weight/day, piceatannol did not reduce either hyperphagia or fat accumulation. It did not modify the profusion of the most abundant phyla in gut, though slight changes were observed in the abundance of several Lactobacillus, Clostridium, and Bacteroides species belonging to Firmicutes and Bacteroidetes. This was accompanied by a tendency to reduce plasma lipopolysaccharides by 30 %, and by a decrease of circulating non-esterified fatty acids, LDL-cholesterol, and lactate. While piceatannol tended to improve lipid handling, it did not mitigate hyperinsulinemia and cardiac hypertrophy. However, it increased cardiac expression of ephrin-B1, a membrane protein that contributes to maintaining cardiomyocyte architecture. Lastly, ascorbyl radical plasma levels and hydrogen peroxide release by adipose tissue were similar in control and treated groups. Thus, piceatannol did not exhibit strong slimming capacities but did limit several obesity complications.

13 pages; International audience; Stat3 (Signal Transducer and Activator of Transcription-3) is activated by a number of receptor and nonreceptor tyrosine kinases. We recently demonstrated that engagement of E-cadherin, a calcium-dependent, cell to cell adhesion molecule which is often required for cells to remain tightly associated within the epithelium, also activates Stat3.We nowexamined the effect of two other classical cadherins, cadherin-11 and N-cadherin,whose expression often correlateswith the epithelial to mesenchymal transition occurring in metastasis of carcinoma cells, upon Stat3 phosphorylation and activity. Our results indicate that engagement of these two cadherins also, can trigger a dramatic surge in Stat3 activity. This activation occurs through upregulation ofmembers of the IL6 family of cytokines, and it is necessary for cell survival, proliferation and migration. Interestingly, our results also demonstrate for the first time that, in sharp contrast to Stat3, the activity of Erk (Extracellular Signal Regulated kinase) was unaffected by cadherin-11 engagement. Further examination indicated that, although IL6 was able to activate Erk in sparsely growing cells, IL6 could not induce an increase in Erk activity levels in densely growing cultures. Most importantly, cadherin-11 knock-down did allow Erk activation by IL6 at high densities, indicating that it is indeed cadherin engagement that prevents Erk activation by IL6. The fact that the three classical cadherins tested so far, E-cadherin, N-cadherin and cadherin11,which are present in essentially all tissues, actually activate Stat3 regardless of their role in metastasis, argues for Stat3 as a central survival, rather than invasion factor.

To the Editor: Eleven years of molecular epidemiologic data allowed the Spanish Multidrug-resistant Tuberculosis (MDR TB) Surveillance Network to identify a specific MDR Mycobacterium tuberculosis strain that had been imported into Spain from Equatorial Guinea (1). Our study brings to light the potential dissemination of this strain (named MDR-TBEG) in Equatorial Guinea, a country where little is known about the extent and features of TB or MDR TB. It also highlights that MDR strains can spread across continents, and thus MDR TB’s emergence in any country becomes a global problem. Ten MDR M. tuberculosis isolates obtained from 10 patients from Equatorial Guinea were detected in Spain during 2000 through 2008. Evidence of clonality was found within the 10 isolates because all exhibited identical genetic profiles defined by different molecular epidemiology methods (2,3) and mutations involved in drug resistance (Figure). Notably, none of the remaining 504 MDR isolates in the Spanish database matched SIT177, a spoligotype belonging to the Latin American–Mediterranean 9 (LAM9) subfamily (4). Figure Genetic profile of the multidrug-resistant tuberculosis Equatorial Guinea (MDR-TBEG) strain. RFLP, restriction fragment length polymorphism; SIT, spoligotype international type; LAM, Latin American-Mediterranean; MIRU-VNTR, mycobacterial interspersed ... The data routinely collected for all cases of MDR TB have been previously described (1). All 10 patients in the study were from Equatorial Guinea, a small African country on the Gulf of Guinea with a population of ≈500,000, an MDR TB rate >2.0% (5) of all combined (new and previously treated) TB cases, and an estimated adult HIV prevalence rate of 3.2% (www.who.int/globalatlas/predefinedReports/EFS2008/full/EFS2008_GQ.pdf). The MDR TB isolates were collected within a 9-year period (Technical Appendix): 1 in 2000, 2 in 2001, 3 in 2003, 1 in 2004, 2 in 2007, and 1 in 2008. According to their hospitals of origin, the patients were geographically dispersed in 6 different Spanish cities. We found that the interval between the patients’ arrival in Spain to the initiation of anti-TB treatment was

Transferrin (Tf), the iron transport glycoprotein found in biological fluids of vertebrates, is synthesized mainly by hepatocytes. Tf is also synthesized by oligodendrocytes (Ol), and several lines of evidence indicate that brain Tf could be involved in myelinogenesis. Because Tf is postnatally expressed in the brain, we sought to investigate whether Tf could intervene in Ol differentiation. For this purpose, we analyzed transgenic mice overexpressing the complete human Tf gene in Ol. We show that the hTf transgene was expressed only from 5 days postpartum onward. In the brain of 14-day-old transgenic mice, the DM-20 mRNA level was decreased, whereas the PLP, MBP, CNP, and MAG mRNA levels were increased. We counted a higher proportion of Ol expressing the O4 (Ol-specific antigens) and PLP in brain cells cultured from transgenic mice. These results support the idea that overexpressing Tf in the brain accelerates the oligodendrocyte lineage maturation. Accordingly, by NMR imaging acquisition of diffusion tensor in hTf transgenic mice, we observed early maturation of the cerebellum and spinal cord and more myelination in the corpus callosum. In addition, hTf overexpression led to an increase in Sox10 mRNA and protein. Increases in Sox10 and in Tf expression occur simultaneously during brain development. The Olig1 mRNA level also increased, but long after the rise of hTf and Sox10. The Olig2 mRNA level remained unchanged in the brain of transgenic mice. Our findings suggest that Tf could influence oligodendrocyte progenitor differentiation in the CNS.

International audience