The Role of SOX2 and SOX9 Transcription Factors in the Reactivation-Related Functional Properties of NT2/D1-Derived Astrocytes.

Astrocytes are the main homeostatic cells in the central nervous system, with the unique ability to transform from quiescent into a reactive state in response to pathological conditions by reacquiring some precursor properties. This process is known as reactive astrogliosis, a compensatory response that mediates tissue damage and recovery. Although it is well known that SOX transcription factors drive the expression of phenotype-specific genetic programs during neurodevelopment, their roles in mature astrocytes have not been studied extensively. We focused on the transcription factors SOX2 and SOX9, shown to be re-expressed in reactive astrocytes, in order to study the reactivation-related functional properties of astrocytes mediated by those proteins. We performed an initial screening of SOX2 and SOX9 expression after sensorimotor cortex ablation injury in rats and conducted gain-of-function studies in vitro using astrocytes derived from the human NT2/D1 cell line. Our results revealed the direct involvement of SOX2 in the reacquisition of proliferation in mature NT2/D1-derived astrocytes, while SOX9 overexpression increased migratory potential and glutamate uptake in these cells. Our results imply that modulation of SOX gene expression may change the functional properties of astrocytes, which holds promise for the discovery of potential therapeutic targets in the development of novel strategies for tissue regeneration and recovery.

The gut microbiome regulates astrocyte reaction to Aß amyloidosis through microglial dependent and independent mechanisms.

BACKGROUND: Previous studies show that antibiotic-mediated (abx) alteration of the gut microbiome (GMB) results in a reduction of amyloid beta (Aß) plaques and proinflammatory microglial phenotype in male APPPS1-21 mice. However, the effect of GMB perturbation on astrocyte phenotypes and microglial-astrocyte communication in the context of amyloidosis has not been examined. METHODS: To study whether the GMB modulates astrocyte phenotype in the context of amyloidosis, APPPS1-21 male and female mice were treated with broad-spectrum abx leading to GMB perturbation. GFAP + astrocytes, plaque-associated astrocytes (PAA), PAA morphological parameters, and astrocyte complement component C3 levels were quantified using a combination of immunohistochemistry, immunoblotting, widefield microscopy, and confocal microscopy. Furthermore, these same astrocyte phenotypes were assessed in abx-treated APPPS1-21 male mice that received either fecal matter transplant (FMT) from untreated APPPS1-21 male donors to restore their microbiome or vehicle control. To assess complete absence of the GMB on astrocyte phenotypes, the same astrocyte phenotypes were quantified in APPPS1-21 male mice raised in germ-free (GF) or specific-pathogen free conditions (SPF). Lastly, we assessed whether microglia are necessary for abx-induced astrocyte phenotypes by depleting microglia in APPPS1-21 male mice via treatment with a colony-stimulating factor 1 receptor (CSF1R) inhibitor (PLX5622) and vehicle control or PLX5622 and abx. RESULTS: Herein, we demonstrate that postnatal treatment of male APPPS1-21 mice with broad-spectrum abx leading to GMB perturbation reduces GFAP + reactive astrocytes and PAAs, suggesting that the GMB plays a role in regulating reactive astrocyte induction and recruitment to Aß plaques. Additionally, we show that compared to controls, PAAs in abx-treated male APPPS1-21 mice exhibit an altered morphology with increased number and length of processes and reduced astrocytic complement C3, consistent with a homeostatic phenotype. GFAP + astrocyte reduction, PAA reduction, astrocyte morphological changes, and C3 levels are restored when abx-treated mice are subject to FMT from untreated APPPS1-21 male donor mice. Next, we found that APPPS1-21 male mice raised in GF conditions have similar astrocyte phenotypes as abx-treated male APPPS1-21 male mice. Correlational analysis revealed that pathogenic bacteria depleted by abx correlate with GFAP + astrocytosis, PAAs, and astrocyte morphological changes. Finally, we determined that abx-mediated reduction in GFAP + astrocytosis, PAAs, and astrocytic C3 expression is independent of microglia. However, abx-induced astrocyte morphological alterations are dependent on the presence of microglia, suggesting that there is both microglial independent and dependent GMB control of reactive astrocyte phenotypes. CONCLUSIONS: We show for the first time, in the context of amyloidosis, that the GMB plays an important role in controlling reactive astrocyte induction, morphology, and astrocyte recruitment to Aß plaques. GMB regulation of these astrocytic phenotypes is both independent and dependent on microglia.

Gene Expression and Early Radiation Response of Two Distinct Neuroblastoma Cell Lines.

INTRODUCTION: Neuroblastoma is one of the most common childhood cancers with one of the lowest survival rates, accounting for 15% of childhood cancer mortality. Approximately half of children treated for high-risk neuroblastoma will relapse following remission, while another 15% of patients do not respond to initial treatment. External beam radiation is infrequently used for treatment of pediatric cancer such as neuroblastoma, typically reserved for palliative care in patients with aggressive metastatic disease who fail to respond to alternative treatments. Understanding effects of radiation on neuroblastoma cells could improve efficacy of this final means of therapy to decrease tumor burden and stabilize the disease. METHODS: In this study, we found that two microRNAs with opposite functions were expressed in two neuroblastoma cell lines with marked differences in radiosensitivity. Clonogenic assays were used to evaluate the radiation responses for these 2 cell lines, designated SK-N-AS and SK-N-DZ; cells were then irradiated at doses that cause 90% cell killing based on clonogenic assay and their RNA isolated and subjected to microarray analysis. In addition, cells were transfected with pre-miRNA constructs that led to overexpression of microRNAs miR-34a and miR-1228 to determine possible microRNA regulation of radiation response. RESULTS: Statistically significant differences were detected for expression of several thousand genes when the 2 cell lines were compared with each other. In comparison, radiation exposure resulted in only minor gene expression differences of less than 2-fold at the 1 h postirradiation timepoint in both cell lines. Overexpression of miR-34a and miR-1228 in either cell line did not alter this outcome. DISCUSSION: While these two neuroblastoma cell lines are phenotypically diverse and gene expression differences between them are extensive, we observed that the regulation of gene expression in both cell lines is in a stable equilibrium at early timepoints after exposure to ionizing radiation.

Unraveling the Reaction Mystery of Li and Na with Dry Air.

Li and Na metals with high energy density are promising in application in rechargeable batteries but suffer from degradation in the ambient atmosphere. The phenomenon that in terms of kinetics, Li is stable but Na is unstable in dry air has not been fully understood. Here, we use in situ environmental transmission electron microscopy combined with theoretical simulations and reveal that the different stabilities in dry air for Li and Na are reflected by the formation of compact Li2O layers on Li metal, while porous and rough Na2O/Na2O2 layers on Na metal are a consequence of the different thermodynamic and kinetics in O2. It is shown that a preformed carbonate layer can change the kinetics of Na toward an anticorrosive behavior. Our study provides a deeper understanding of the often-overlooked chemical reactions with environmental gases and enhances the electrochemical performance of Li and Na by controlling interfacial stability.

Lessons learned in the practice of community-based participatory research with community partner collaboration in study design and implementation: the community scientist model.

Engagement of community participation is an innovative driver of modern research. However, to benefit the communities being studied, it is imperative to continuously evaluate ethical considerations, the relationship dynamic between researchers and community members, and the responsiveness of research teams to the needs and preferences of communities. Northwestern University's Center for Health Equity Transformation founded a community scientist program in 2018 that implemented a study using the Community-Based Participatory Research (CBPR) model. This project is an ongoing study of heavy metal exposure by geographic location in Chicago. Community scientists from various backgrounds, communities, and organizations formed an advisory panel, partnering with the cancer research team. This commentary describes lessons learned in structuring meaningful community involvement and benefit in CBPR, with a focus on three lessons learned that relate to ethics, relationships, and responsiveness. Our findings lay new groundwork for iteratively shaping best practices in CBPR.

In vitro effect of beer, red and white wine on the morphology and surface roughness of human enamel.

BACKGROUND: Beer, red and white wine are acidic drinks whose frequent consumption can increase the risk of dental erosion. OBJECTIVES: To establish the effect of beer, red and white wine on the morphology and surface roughness (SR) of human enamel using different exposure times in a cyclic deand remineralization model in vitro. MATERIAL AND METHODS: The experiment included 33 surgically extracted impacted human third molars from patients aged 18-25 years. Enamel samples obtained by cutting crowns (n = 132) were submitted to alternate cycles of demineralization in (1) beer, (2) red wine, (3) white wine, (PC) positive control (orange juice), and remineralization in artificial saliva, which also represented a medium for negative control (NC). The experiment included cycles with different exposure times in alcoholic beverages and orange juice of 15, 30 and 60 min. Thus, 12 groups were formed (for each drink and each exposure time) containing 10 samples each, while the NC group consisted of 12 samples. Experiments were repeated 3x/day for 10 days. Enamel surface alterations were determined by stylus profilometry (average surface roughness (Ra)) and scanning electron microscopy (SEM). The Shapiro-Wilk test, independent samples Kruskal-Wallis test and multiple comparisons (all pairwise) were performed. RESULTS: With increasing exposure time, there was a positive correlation with Ra for white wineand orange juice-immersed samples (60 min compared to 15 min), which was also observed using SEM. There was no significant difference in the Ra between the other experimental samples for the same exposure time. CONCLUSIONS: This study confirms a certain erosive potential of beer, red and white wine, and a significant relationship with pH, titratable acidity (TA) and SR, but not with the exposure time for all tested alcoholic beverages. Moreover, differences among the ultrastructural patterns caused by alcoholic beverages over the enamel surface were observed.

Effects of Autoclave Sterilization on Cyclic Fatigue Resistance in 5 Types of Rotary Endodontic Instruments: An In Vitro Study.

BACKGROUND Rotary endodontic instruments are increasingly used in root canal treatment and have replaced stainless steel manual files. Cyclic fatigue is the cyclic loading of stress to produce deformation or fracture. This study aimed to evaluate and compare the effects of autoclave sterilization on cyclic fatigue in 5 types of rotary endodontic instruments. MATERIAL AND METHODS ProTaper Universal, BioRace, ProTaper Next, Twisted File, and HyFlex CM instruments were included in this study. Each type included 96 instruments, divided into 4 groups according to the number of sterilization cycles (0, 1, 3, 5). After sterilization, each group of instruments was divided into 2 subgroups and tested for cyclic fatigue in 2 simulated canals (45 degrees both and 2 radii, 2 mm and 5 mm). The number of cycles to failure (NCF) was calculated, and statistical analyses were carried out using the t test, Mann-Whitney U test, and ANOVA, followed by the Tukey post hoc test (p<0.05). Fracture surfaces were analyzed using scanning electron microscopy (SEM). RESULTS Within the group of non-sterilized instruments, ProTaper Universal showed significantly lower resistance to cyclic fatigue compared to the other types of instruments (p<0.001). After repeated sterilization, a significantly higher mean of NCF was observed for BioRace (p<0.001), ProTaper Next (p<0.001), Twisted File (p<0.001), and HyFlex CM (p<0.001) compared to ProTaper Universal. The resistance of HyFlex CM was significantly higher compared to the other types of instruments (p<0.001). CONCLUSIONS The findings from this study showed that autoclave sterilization of newer rotary endodontic instruments could increase resistance to cyclic fatigue.

Determining the Impact of the COVID-19 Pandemic on Dental Care in the Serbian Adult Population: An Online Questionnaire-Based Study.

BACKGROUND Emergence of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 virus) could lead to an increase in dental anxiety, avoidance of dental visits, and general neglect of oral health. This online questionnaire-based study conducted in April and May of 2021 in Serbia aimed to determine the impact of the coronavirus disease 2019 (COVID-19) pandemic on dental care. MATERIAL AND METHODS The study included 2060 adult citizens of the Republic of Serbia who participated in an anonymous online questionnaire based on a 5-point Likert scale. Data were collected on dental care routine prior to and during the pandemic, and the fear of negative consequences for oral health. The results were statistically analyzed using descriptive statistics, Pearson's correlation coefficient, ANOVA, and the paired t test. RESULTS Approximately one-fifth of the respondents postponed dental visits during the pandemic. Concern about postponing dental treatment was expressed by more than one-half of the respondents (57.1%), while 21.4% thought that they were already experiencing the consequences. Avoidance of preventive examinations and improvement of oral hygiene are more common among the elderly compared to younger respondents (P=.000). CONCLUSIONS The COVID-19 pandemic did not significantly affect the habit of avoiding dental interventions due to fear, but it did lead to part of the population completely avoiding even urgent dental interventions during the peak of the pandemic, and opting for tooth extraction rather than treatment. The strongest impact on dental care in the pandemic was among people over 64 years old.

Aberrant glial activation and synaptic defects in CaMKIIα-iCre and nestin-Cre transgenic mouse models.

Current scientific research is driven by the ability to manipulate gene expression by utilizing the Cre/loxP system in transgenic mouse models. However, artifacts in Cre-driver mouse lines that introduce undesired effects and confound results are increasingly being reported. Here, we show aberrant neuroinflammation and synaptic changes in two widely used Cre-driver mouse models. Neuroinflammation in CaMKIIα-iCre mice was characterized by the activation and proliferation of microglia and astrocytes in synaptic layers of the hippocampus. Increased GFAP and Iba1 levels were observed in hippocampal brain regions of 4-, 8- and 22-month-old CaMKIIα-iCre mice compared to WT littermates. Synaptic changes in NMDAR, AMPAR, PSD95 and phosphorylated CaMKIIα became apparent in 8-month-old CaMKIIα-iCre mice but were not observed in 4-month-old CaMKIIα-iCre mice. Synaptophysin and synaptoporin were unchanged in CaMKIIα-iCre compared to WT mice, suggesting that synaptic alterations may occur in excitatory postsynaptic regions in which iCre is predominantly expressed. Finally, hippocampal volume was reduced in 22-month-old CaMKIIα-iCre mice compared to WT mice. We tested the brains of mice of additional common Cre-driver mouse models for neuroinflammation; the nestin-Cre mouse model showed synaptic changes and astrocytosis marked by increased GFAP+ astrocytes in cortical and hippocampal regions, while the original CaMKIIα-Cre T29-1 strain was comparable to WT mice. The mechanisms underlying abnormal neuroinflammation in nestin-Cre and CaMKIIα-iCre are unknown but may be associated with high levels of Cre expression. Our findings are critical to the scientific community and demonstrate that the correct Cre-driver controls must be included in all studies using these mice.

Findings from international archived data: Fractionation reduces mortality risk of ionizing radiation for total doses below 4 Gray in rodents.

Ionizing radiation is omnipresent and unavoidable on Earth; nevertheless, the range of doses and modes of radiation delivery that represent health risks remain controversial. Radiation protection policy for civilians in US is set at 1 mSv per year. Average persons from contemporary populations are exposed to several hundred milliSieverts (mSv) over their lifetimes from both natural and human made sources such as radon, cosmic rays, CT-scans (20-50 mSv partial body exposure per scan), etc. Health risks associated with these and larger exposures are focus of many epidemiological studies, but uncertainties of these estimates coupled with individual and environmental variation make it is prudent to attempt to use animal models and tightly controlled experimental conditions to supplement our evaluation of radiation risk question. Data on 11,528 of rodents of both genders exposed to x-ray or gamma-ray radiation in facilities in US and Europe were used for this analysis; animal mortality data argue that fractionated radiation exposures have about 2 fold less risk per Gray than acute radiation exposures in the range of doses between 0.25 and 4 Gy.

COVID-19: Another Cause of Dental Anxiety?

BACKGROUND Fear has always been closely linked to dentistry but it could be intensified by the objective risks imposed by the pandemic. The objective of this study was to determine the profile of the frightened dental patient during the COVID-19 pandemic and determine measures taken by dentists to reduce fear and increase security among their patients. MATERIAL AND METHODS An anonymous online survey was conducted between March 15 and April 15, 2021. The respondents were 2060 adult citizens of the Republic of Serbia. In addition to demographic data, data related to the COVID-19 pandemic, dental fear, and attitudes and fear of dental interventions during the ongoing pandemic were compiled. The data were analyzed using descriptive statistics: the chi-square test and Pearson's coefficient. RESULTS Seventy percent of the respondents felt some level of fear of the ongoing pandemic, 50% felt fear of going to a dentist during the pandemic, 20% considered a dental office a hotspot for the transmission of SARS-CoV-2, and 43% would visit their dentist only in the case of emergency. CONCLUSIONS The COVID-19 pandemic has affected the attitudes and behavior of people pertaining to visits to dental offices. Identifying frightened patients and their opinions and fears at this challenging time would make it easier for dentists to include protocols in their everyday practice to increase a sense of security among their patients, such as implementing preventive measures in front of the patients, ensuring an empty waiting room, and providing telephone consultations.

Poloxamer-188 Exacerbates Brain Amyloidosis, Presynaptic Dystrophies, and Pathogenic Microglial Activation in 5XFAD Mice.

BACKGROUND: Alzheimer's disease (AD) is initiated by aberrant accumulation of amyloid beta (Aß) protein in the brain parenchyma. The microenvironment surrounding amyloid plaques is characterized by the swelling of presynaptic terminals (dystrophic neurites) associated with lysosomal dysfunction, microtubule disruption, and impaired axonal transport. Aß-induced plasma membrane damage and calcium influx could be potential mechanisms underlying dystrophic neurite formation. OBJECTIVE: We tested whether promoting membrane integrity by brain administration of a safe FDA approved surfactant molecule poloxamer-188 (P188) could attenuate AD pathology in vivo. METHODS: Three-month-old 5XFAD male mice were administered several concentrations of P188 in the brain for 42 days with mini-osmotic pumps. After 42 days, mice were euthanized and assessed for amyloid pathology, dystrophic neurites, pathogenic microglia activation, tau phosphorylation, and lysosomal / vesicular trafficking markers in the brain. RESULTS: P188 was lethal at the highest concentration of 10mM. Lower concentrations of P188 (1.2, 12, and 120µM) were well tolerated. P188 increased brain Aß burden, potentially through activation of the γ-secretase pathway. Dystrophic neurite pathology was exacerbated in P188 treated mice as indicated by increased LAMP1 accumulation around Aß deposits. Pathogenic microglial activation was increased by P188. Total tau levels were decreased by P188. Lysosomal enzyme cathepsin D and calciumdependent vesicular trafficking regulator synaptotagmin-7 (SYT7) were dysregulated upon P188 administration. CONCLUSION: P188 brain delivery exacerbated amyloid pathology, dystrophic neurites, and pathogenic microglial activation in 5XFAD mice. These effects correlated with lysosomal dysfunction and dysregulation of plasma membrane vesicular trafficking. P188 is not a promising therapeutic strategy against AD pathogenesis.

Influence of Porosity of Sulfide-Based Artificial Solid Electrolyte Interphases on Their Performance with Liquid and Solid Electrolytes in Li and Na Metal Batteries.

Realization of all-solid-state batteries combined with metallic Li/Na is still hindered due to the unstable interface between the alkali metal and solid electrolytes, especially for highly promising thiophosphate materials. Artificial and uniform solid-electrolyte interphases (SEIs), serving as thin ion-conducting films, have been considered as a strategy to overcome the issues of such reactive interfaces. Here, we synthesized sulfide-based artificial SEIs (LixSy and NaxSy) on Li and Na by solid/gas reaction between the alkali metal and S vapor. The synthesized films are carefully characterized with various chemical/electrochemical techniques. We show that these artificial SEIs are not beneficial from an application point of view since they either contribute to additional resistances (Li) or do not prevent reactions at the alkali metal/electrolyte interface (Na). We show that NaxSy is more porous than LixSy, supported by (i) its rough morphology observed by focused ion beam-scanning electron microscopy, (ii) the rapid decrease of Rinterface (interfacial resistance) in NaxSy-covered-Na symmetric cells with liquid electrolyte upon aging under open-circuit potential, and (iii) the increase of Rinterface in NaxSy-covered-Na solid-state symmetric cells with Na3PS4 electrolyte. The porous SEI allows the penetration of liquid electrolyte or alkali metal creep through its pores, resulting in a continuous chemical reaction. Hence, porosity of SEIs in general should be carefully taken into account in the application of batteries containing both liquid electrolyte and solid electrolyte.

Oral nimodipine treatment has no effect on amyloid pathology or neuritic dystrophy in the 5XFAD mouse model of amyloidosis.

Dysregulation of calcium homeostasis has been hypothesized to play a role in Alzheimer's disease (AD) pathogenesis. Increased calcium levels can impair axonal transport, disrupt synaptic transmission, and ultimately lead to cell death. Given the potential role of calcium dyshomeostasis in AD, there is interest in testing the ability of already approved drugs targeting various calcium channels to affect amyloid pathology and other aspects of disease. The objective of this study was to test the effects of FDA-approved L-type calcium channel antagonist nimodipine on amyloid accumulation and dystrophic neurite formation in 5XFAD mice, a mouse model of amyloid pathology. 5XFAD transgenic mice and non-transgenic littermates were treated with vehicle or nimodipine-containing chow from two to eight months of age, then brains were harvested and amyloid pathology assessed by immunoblot and immunofluorescence microscopy analyses. Nimodipine was well tolerated and crossed the blood brain barrier, as expected, but there was no effect on Aß accumulation or on the relative amount of neuritic dystrophy, as assessed by either immunoblot, dot blot or immunofluorescence imaging of Aß42 and dystrophic neurite marker LAMP1. While we conclude that nimodipine treatment is not likely to improve amyloid pathology or decrease neuritic dystrophy in AD, it is worth noting that nimodipine did not worsen the phenotype suggesting its use is safe in AD patients.

Insights into Cationic Transference Number Values and Solid Electrolyte Interphase Growth in Liquid/Solid Electrolytes for Potassium Metal Batteries.

Liquid/solid battery electrolytes make separators dispensable and enable a high cationic transference number with liquid-like room temperature ionic conductivity. This work gives insights into electrochemical behavior (galvanostatic polarization and time-dependent impedance spectroscopy) of liquid/solid electrolytes containing potassium salts in battery cells enclosing potassium metal anodes. Very high potassium transference numbers (t K = 0.88) are observed in carbonate-based electrolytes, linked with long-term mechanical instability of the solid electrolyte interphase on the potassium anode. In the case of glyme-based electrolytes, electrochemical behavior indicates the existence of the highly porous solid electrolyte interphase and additional surface porosity of the potassium electrode.

Porosity of Solid Electrolyte Interphases on Alkali Metal Electrodes with Liquid Electrolytes.

Despite the fact that solid electrolyte interphases (SEIs) on alkali metals (Li and Na) are of great importance in the utilization of batteries with high energy density, growth mechanism of SEIs under an open-circuit potential important for the shelf life and the nature of ionic transport through SEIs are yet poorly understood. In this work, SEIs on Li/Na formed by bringing the electrodes in contact with ether- and carbonate-based electrolyte in symmetric cells were systematically investigated using diverse electrochemical/chemical characterization techniques. Electrochemical impedance spectroscopy (EIS) measurements linked with activation energy determination and cross-section images of Li/Na electrodes measured by ex situ FIB-SEM revealed the liquid/solid composite nature of SEIs, indicating their porosity. SEIs on Na electrodes are shown to be more porous compared to the ones on Li in both carbonate and glyme-based electrolytes. Nonpassivating nature of such SEIs is detrimental for the performance of alkali metal batteries. We laid special emphasis on evaluating time-dependent activation energy using EIS.

Development of Multi-Scale X-ray Fluorescence Tomography for Examination of Nanocomposite-Treated Biological Samples.

Research in cancer nanotechnology is entering its third decade, and the need to study interactions between nanomaterials and cells remains urgent. Heterogeneity of nanoparticle uptake by different cells and subcellular compartments represent the greatest obstacles to a full understanding of the entire spectrum of nanomaterials' effects. In this work, we used flow cytometry to evaluate changes in cell cycle associated with non-targeted nanocomposite uptake by individual cells and cell populations. Analogous single cell and cell population changes in nanocomposite uptake were explored by X-ray fluorescence microscopy (XFM). Very few nanoparticles are visible by optical imaging without labeling, but labeling increases nanoparticle complexity and the risk of modified cellular uptake. XFM can be used to evaluate heterogeneity of nanocomposite uptake by directly imaging the metal atoms present in the metal-oxide nanocomposites under investigation. While XFM mapping has been performed iteratively in 2D with the same sample at different resolutions, this study is the first example of serial tomographic imaging at two different resolutions. A cluster of cells exposed to non-targeted nanocomposites was imaged with a micron-sized beam in 3D. Next, the sample was sectioned for immunohistochemistry as well as a high resolution "zoomed in" X-ray fluorescence (XRF) tomography with 80 nm beam spot size. Multiscale XRF tomography will revolutionize our ability to explore cell-to-cell differences in nanomaterial uptake.

Environmental signals rather than layered ontogeny imprint the function of type 2 conventional dendritic cells in young and adult mice.

Conventional dendritic cells (cDC) are key activators of naive T cells, and can be targeted in adults to induce adaptive immunity, but in early life are considered under-developed or functionally immature. Here we show that, in early life, when the immune system develops, cDC2 exhibit a dual hematopoietic origin and, like other myeloid and lymphoid cells, develop in waves. Developmentally distinct cDC2 in early life, despite being distinguishable by fate mapping, are transcriptionally and functionally similar. cDC2 in early and adult life, however, are exposed to distinct cytokine environments that shape their transcriptional profile and alter their ability to sense pathogens, secrete cytokines and polarize T cells. We further show that cDC2 in early life, despite being distinct from cDC2 in adult life, are functionally competent and can induce T cell responses. Our results thus highlight the potential of harnessing cDC2 for boosting immunity in early life.