Browse Articles

Space‐Time‐Frequency Information Metasurface and Its Application in Electromagnetic Environment Sensing

ABSTRACT The advancement of 6G communications, Internet of Things, and electronic warfare systems toward higher frequencies, wider bandwidths, and multi‐scenario cooperation has imposed increasingly stringent demands on real‐time and high‐precision electromagnetic field sensing. However, the efficiency‐complexity trade‐off persists as a critical bottleneck for conventional sensing approaches in the space, time and space‐time domains. To address this problem, we propose a space‐time‐frequency information metasurface and investigate its applications in electromagnetic environment sensing. By incorporating differentiated frequency‐shift digital coding into meta‐atoms, different meta‐atoms will modulate distinct characteristic frequencies independently, resulting in a space‐time‐frequency coding strategy. The joint coding strategy enables efficient decoupling and parallel extraction of atom‐level electromagnetic signals in frequency domain under a single radio‐frequency reception channel, significantly reducing the system complexity and hardware costs. This method extends the modulation dimensions of information metasurface to the space‐time‐frequency coding, and may pave a new pathway for high‐dimensional electromagnetic signal processing and sensing systems.

TESCLA: A Fully Soft Electromagnetic Linear Actuator With Continuous Bending Enabled by Liquid‐Metal Solenoids

ABSTRACT Linear actuators are widely employed in robots and wearable devices due to their capability of directly generating linear motion. Although soft actuators and flexible linear actuators have been developed to enable effective operation in various configurations, they are still constrained by a limited actuation range and a discrete bending, which restricts their achievable workspace and curvatures. Here, we propose a tubular electromagnetic soft conformal linear actuator (TESCLA) exerting thrust force over a large actuation stroke with continuous bending. The actuator operates under both a straight configuration and a conformal deformation to the surrounding environment, leveraging the softness of liquid‐metal solenoids (soft stator) and compliant magnetic composites (soft mover). The synchronous actuation strategy allows the actuator to produce controllable bidirectional electromagnetic thrust by applying an electric current to the soft stator. In addition, the step position is estimated by measuring inductance variance of the soft solenoids resulting from the displacement of the soft mover. The design of the actuator components is evaluated through numerical simulations to determine an effective configuration, considering performance characteristics such as thrust force, minimum step size, and sensing resolution. By utilizing the functionalities of the proposed actuator, biomimetic robotic applications and a wearable haptic device were demonstrated.

Nondestructive Integration of Laser‐Induced Biomass Graphene for Sustainable Wearable Electronics

ABSTRACT Laser‐induced graphene (LIG) circuits hold significant promise for wearable electronics due to their excellent chemical stability and biocompatibility. However, fossil‐derived aromatic precursors are challenged by limited availability and environmental burden, and high energy laser processing damages substrates and hinders separation. Here, we propose a nondestructive strategy that integrates rapid heat dissipation and stress‐free pattern transfer based on a botanical lignin‐based precursor. Guided by the ReaxFF molecular dynamics simulation on the decomposition and reconstruction processes, lignin‐derived LIG circuits with high‐ordered structure and sheet resistance as low as 15 Ω sq −1 are obtained, and allow for complete integration onto a wide range of polymers, including those with ultrathin (20 µm), low‐modulus (69 kPa), and low‐melting‐point (84°C) profiles previously inaccessible. Leveraging the above platforms, six flexible devices irradiating light, electron, and thermal sensing applications are constructed, demonstrating its universality. Last but not the least, lignin offers high biosynthetic yield, closed‐loop recyclability, and excellent biodegradability, achieving an approximately 90% reduction in environmental footprint compared to fossil‐based alternatives.

Coherent Solid–Solution Interface With Near‐Zero Lattice Mismatch Enables Stable Zinc Anodes

ABSTRACT Aqueous Zn‐ion batteries (AZIBs) are attractive for large‐scale energy storage owing to their high theoretical capacity, intrinsic safety, and low cost. However, interfacial instability of Zn metal remains a major obstacle, leading to dendritic growth, parasitic reactions, and rapid capacity decay. Here, we introduce a coherent solid–solution interface (SSI) strategy with near‐zero lattice mismatch to stabilize the Zn metal anode. The in situ formed SSI exhibits a lattice mismatch of only 0.11% with Zn, enabling coherent Zn growth and suppressing detrimental side reactions. Combined experimental and theoretical analyses reveal that the SSI reduces interfacial polarization, suppresses HER, and promotes uniform lattice‐aligned dense Zn deposition. As a result, SSI‐Zn delivers stable Zn||Zn symmetric cell cycling for over 9100 h (1 year and 18 days) and achieves Zn||Cu asymmetric cell performance with a Coulombic efficiency (CE) of 99.9% over 10 000 cycles. In full cell configurations, Zn||AC cells and Zn||I 2 cells operate stably for over 120 000 cycles and 17 000 cycles, respectively, with average CE (ACE) values of 99.6% and 99.99%. Furthermore, an anode‐free Zn||Br pouch cell operates stably at an areal capacity of 5 mAh cm −2 with 99.4% ACE, achieving a practical energy density of 61 Wh kg −1 . By coupling near‐zero lattice mismatch with interfacial stabilization, this work demonstrates coherent interface engineering as a promising strategy toward high‐energy and long‐lifespan AZIBs.

Advancing 1.84 eV Wide‐Bandgap Perovskite Photovoltaics Beyond 20% via Single‐Facet‐Oriented Self‐Assembled Molecules

ABSTRACT Uncontrolled crystal growth and structural heterogeneity in solution‐processed self‐assembled molecules (SAMs) remain major limitations for efficient interfacial charge transport. Herein, we report a dipole‐engineered molecular strategy to regulate SAMs crystallization through the rational design of fluorinated benzimidazole‐carboxylic acid (BzIm‐COOH) derivatives (1F‐COOH, 2F‐COOH, and 3F‐COOH). Co‐assembly of these molecules with the parent SAMs induces strong electrostatic and dipole‐dipole interactions that direct crystal growth along the (100) facet, converting the SAMs layer from a polyfaceted, disordered morphology into a highly oriented architecture. Among them, 3F‐COOH, possessing the largest molecular dipole moment, exhibits the most pronounced facet‐directing capability. In addition to structural regulation, the BzIm‐COOH molecules optimize the interfacial energetics at the hole‐transport‐layer/perovskite junction, enabling more efficient hole extraction. Meanwhile, strong chemical interactions between 3F‐COOH and the perovskite precursor regulate crystallization kinetics and passivate interfacial defects. Consequently, wide‐bandgap (1.84 eV) PSCs incorporating 3F‐COOH deliver a champion efficiency of 20.16% (certified 19.25%) with markedly improved operational stability (90.38% after 600 h). The strategy further enables 26.75% perovskite/organic tandem devices and extends to 1.67 eV perovskite devices (23.56%) and perovskite/silicon tandems (32.34%, certified 31.54%). This work establishes dipole‐engineered molecular engineering as a powerful approach for directing SAMs crystallography and optimizing charge‐selective interfaces.

Low‐Dimensional V–VI van der Waals Compound Photodetectors

ABSTRACT This review for the first time provides a comprehensive overview on the low‐dimensional V–VI van der Waals compounds‐based photodetectors. It begins with the fundamental physical mechanisms for photodetection and the properties of various V–VI van der Waals compounds. Then, the preparation methods for producing low‐dimensional V–VI compounds have been presented. Following this, various photodetectors based on low‐dimensional V–VI compounds with distinct characteristics have been epitomized by categorizing them into trivial semiconductors and non‐trivial topological insulators. Subsequently, photodetectors built of V–VI compounds based heterostructures have been introduced, elaborating on the collaborative benefits enabled by heterostructuring. In the end, the future directions of this burgeoning domain have been proposed. On the whole, this review presents a full landscape of low‐dimensional V–VI van der Waals compound photodetectors, underscoring alternative paradigms for the implementation of the next generation of advanced optoelectronic devices and systems.

Reclaiming Reactive Oxygen Species With Taurine/Peroxytaurine Redox Couple for Achieving Ultra‐Long‐Term Cycle Stability in 4.8 V Li‐Rich Layered Oxide Cathodes

ABSTRACT Li‐rich Mn‐based layered oxides (LRMOs) are essential cathode materials for higher energy densities in batteries. Nevertheless, the release of reactive oxygen species (ROS) at high voltages, accompanied by the migration of surface oxygen vacancies and transition metal ions, results in continuous electrolyte decomposition, irreversible phase transition, and nanovoids formation within bulk materials. These processes significantly shorten cycle life of batteries and limit practical applications. Herein, inspired by biological properties of taurine (TA) in scavenging ROS, we propose a straightforward cathode additive strategy by employing TA to effectively interact with ROS, thereby generating a reversible TA/peroxotaurine redox couple. This innovative mechanism enables efficient recycling of ROS, which in turn inhibits continuous electrolyte decomposition, O 2 release, and nanovoid formation. Furthermore, the derived high‐quality cathode electrolyte interphase layer, which is rich in inorganic components and thinner in structure, stabilizes the layered structure while ensuring efficient Li + transport kinetics. Consequently, the modified LRMO demonstrates an exceptional initial Coulombic efficiency of 89% (vs. 81% for LRMO), and a splendid capacity retention of 92% at 1C after 400 cycles (vs. 68% for LRMO). Additionally, the pouch cell paired with graphite anodes exhibits superior capacity retention of 78% after 1000 ultra‐long cycles at 1/3C.

Analog Tensor Processing With Carbon Nanotube In‐Memory Matrix Multiplications for Edge Computer Vision Acceleration

ABSTRACT Computer vision requires intense tensor operations, primarily matrix multiplications, imposing substantial computation demands. Using hardware such as GPU and ASICs for acceleration offers a viable solution. Their application at edge, however, can be constrained by complexity in the computing architecture and incompatibility with analog systems. Here, we prototype an analog tensor core based on carbon nanotube charge‐trapping nonvolatile memory for edge computer vision acceleration. The memory, exhibiting ∼100 linear, symmetric analog weights with fast programming (500 ns) and data processing (1 Mbit/s), enables in‐memory matrix multiplications, facilitating compact tensor core design and operation of vectors and scalars in visual tasks. As demonstrations, the analog tensor core proves three‐dimensional (3D) spatial transformation with an error of <2.81% and edge detection with a signal‐to‐noise ratio of >22 dB, underpinning its potential for accelerating computer vision tasks in, for example, autonomous driving, VR/AR, robot navigation, and industrial automation. Proof‐of‐concept simulation achieves viewfield distortion correction and edge detection of street view fisheye captures by parallel single‐layer tensor processing using our analog tensor core in large scales.

The role of the locus coeruleus in eye movements during perceptual decision making

The locus coeruleus (LC) is the primary source of norepinephrine in the brain and has been implicated in the processes of attention, arousal, and perceptual decision making. Although prior work has linked transient LC activation to both sensory stimulus processing and motor processing, the precise contribution of LC to the distinct sensory and motor components of perceptual decisions remains unclear. Here, we recorded the spiking activity of single LC neurons in rhesus macaques (1 male, 1 female) while they performed a visual two-alternative forced-choice change detection task with a saccadic report, designed to cleanly dissociate sensory and motor contributions to LC activity. We found that the large majority of recorded neurons showed robust increases in response tightly locked to the choice saccade, while only a small fraction showed significant responses to the visual stimuli. Saccade-aligned LC responses did not vary with behavioral outcome, perceptual difficulty, reaction time, or session-wide fluctuations in perceptual sensitivity and criterion, indicating that LC motor-related signals were dissociated from perceptual performance. Together, these results demonstrated the existence of a subpopulation of LC neurons whose activity was tightly coupled to oculomotor output across both voluntary and involuntary eye movements during perceptual decision making, but were independent of perceptual decision accuracy. Our findings support a role for LC in facilitating motor preparation and execution in response to behaviorally significant sensory events. Significance Statement The locus coeruleus has been implicated as a main source of changes in the state of the brain through its brain-wide neuromodulatory inputs. We recorded from this deep brain structure during a task that helped separately assess how it contributes to sensory signals and eye movements to report a decision. We found that the locus coeruleus has activity consistent with a role in facilitating motor preparation relevant to perceptual decisions.

Stage-dependent effects of “too little and too much” medial prefrontal activity on reversal learning in rats: functional inhibition impairs early, whereas neural disinhibition impairs late reversals

Schizophrenia is associated with prefrontal cortex dysfunction, including neural disinhibition (reduced GABAergic inhibition) and hypoactivation (‘hypofrontality’), alongside impaired reversal learning. However, evidence implicating prefrontal regions, including the rodent medial PFC (mPFC), in reversal learning is mixed. mPFC involvement may scale with demand for mPFC-dependent attention and cognitive control to overcome prepotent responses and to learn that reward contingencies can reverse, which is highest during early reversals. We therefore hypothesized that (1) the mPFC is required for early reversal learning but less important when reversal proficiency is high during late reversals. Furthermore, mPFC disinhibition may impair cognitive performance by causing circuit-level disruption outside the mPFC. Therefore, we hypothesized that (2) even when the mPFC is not required, mPFC disinhibition may impair reversal performance. To test hypotheses (1) and (2), we first examined the effect of mPFC functional inhibition and disinhibition, by microinfusion of the GABA-A receptor agonist muscimol and antagonist picrotoxin, on early reversals (reversals 1-3) versus late reversals (reversal 5 onwards) on a 2-lever discrimination task in adult male rats. mPFC functional inhibition by muscimol impaired only early reversals, increasing perseveration and impairing lose-shift behavior at reversal 2. In contrast, mPFC disinhibition by picrotoxin impaired late reversals, reducing lose-shift and win-stay behavior. Using chemogenetic mPFC disinhibition (hM4Di-mediated inhibition of GABAergic neurons), we further tested hypothesis (2). Similar to mPFC picrotoxin, chemogenetic mPFC disinhibition impaired late reversals, primarily disrupting win-stay behavior. Our findings suggest that reduced and disinhibited mPFC activity impair distinct aspects of reversal learning. Significance statement Schizophrenia is associated with reduced activation (“hypofrontality”) and neural disinhibition (reduced GABAergic inhibition) within the prefrontal cortex (PFC). However, it is not clear if and how these distinct aspects of prefrontal dysfunction contribute to impaired reversal learning, a key feature of the cognitive inflexibility characterizing schizophrenia. Here, we combined bi-directional manipulations of prefrontal GABAergic inhibition with testing of reversal learning in rats. Increasing prefrontal functional inhibition (i.e., reducing prefrontal activation) selectively impaired early reversals, enhancing perseveration and reducing lose-shift behavior, whereas prefrontal disinhibition disrupted late reversals, impairing both lose-shift and win-stay behavior. Our findings suggest that reduced activation and disinhibition of PFC disrupt distinct aspects of reversal learning, by distinct mechanisms.

Non-overlapping social and sucrose reward representations in the basolateral amygdala

Animals must continually evaluate the relative value of social and nonsocial rewards to guide adaptive behavior. While both food and social stimuli engage overlapping reward networks, how these reward types are represented within specific nodes of the circuit remains unresolved. The basolateral amygdala (BLA), a region critical for valence and motivational processing, has been implicated in encoding both shared and distinct representations of social and food stimuli. Using in vivo calcium imaging in freely behaving male and female mice performing a two-choice social-sucrose operant task, we examined how individual BLA neurons encode these two different rewards within the same behavioral framework. We found that largely non-overlapping populations of BLA neurons respond to social and sucrose rewards, revealing distinct representational subspaces for each reward type. Under baseline conditions both sexes robustly encoded social and sucrose rewards, but water deprivation revealed a pronounced sex difference, shifting representations toward sucrose reward in females. Populations of sucrose reward responsive neurons in the BLA were selectively sensitive to reward omission. Specifically, sucrose-excited neurons were more strongly modulated by the absence of expected reward than sucrose-inhibited neurons, suggesting a key role for these neurons in signaling reward prediction violations. Together, these findings demonstrate that the BLA encodes social and sucrose rewards through distinct, state-dependent, and functionally heterogeneous neuronal populations, highlighting region-specific strategies for representing reward identity and internal motivational context. Significance Statement The brain’s capacity to weigh different types of rewards, like sucrose versus social interaction, is fundamental to survival yet remains poorly understood. By imaging neuronal activity in the basolateral amygdala (BLA) as mice freely choose between social and sucrose rewards, we found that largely distinct populations of BLA neurons encode each reward type. Internal state selectively altered the recruitment of reward-responsive BLA neurons in a sex-dependent manner. We further show that individual BLA neurons are differentially sensitive to the omission of expected rewards based on baseline responses. Together, these findings highlight the functional diversity through which the brain assigns value across reward modalities and dynamically adapts to changing motivational states.

Neuronal mechanisms mediating long-lasting changes in signal processing also influence neurovascular coupling in the rat hippocampus

To investigate how altered neural signal processing influences fMRI-BOLD responses in the hippocampus, we performed simultaneous in vivo electrophysiology and BOLD-fMRI in male Wistar rats during electrical stimulation of the perforant pathway. By defining input activity via applied pulses and measuring output activity through population spikes, we were able to identify qualitative and quantitative changes in signal processing once the relationship between input and output changed. An initial series of three low-intensity stimulations (LIS) induced clear, consistent BOLD responses. However, following a high-intensity stimulation (HIS) that triggered brief neuronal after-discharges, subsequent series of three identical LIS resulted in significantly attenuated BOLD responses. Electrophysiological data revealed that while total neuronal activity remained stable across all LIS, only the initial LIS induced long-lasting changes in signal processing (persisting beyond 1 minute) and transiently increased gamma band activity. By contrast, after HIS, these changes were reversed and could no longer be re-induced, coinciding with the absence of further increases in gamma band activity. Pharmacological experiments using MK801 and isoflurane further demonstrated that the mechanisms underlying long-lasting changes in signal processing also enhance LIS-induced BOLD responses. These findings suggest that positive fMRI-BOLD responses reflect functionally relevant changes in neural network properties—such as long-lasting modifications in signal processing—rather than simple increases in total neuronal output. Significance Statement An increase in BOLD fMRI signal in a specific brain region is generally interpreted as reflecting increased neuronal activity, with larger increases taken to indicate higher levels of activity. Here, we show that identical inputs can elicit stronger BOLD responses when they also induce long-lasting changes in local network properties, even when the overall activity of principal neurons remains similar. This suggests that the BOLD response is better understood as an indicator of functionally relevant changes in local network processing rather than a purely quantitative measure of neuronal activity.

NOTCHing the MSC-endothelial interplay in the HSC niche

Procr+ endothelial progenitor cells govern hematopoiesis through fine-tuning mesenchymal stem cell niche signals

Abstract Hematopoietic stem cells (HSCs) rely on specialized niche cells for their maintenance, yet how these regulators functionally integrate to preserve hematopoiesis remains unknown. In this study, we identified a subset of protein C receptor–positive (Procr+) endothelial cells (ECs) with progenitor-like properties in bone marrow (BM) which is critical for vascular homeostasis and regeneration after injury. Endothelial-specific ablation of Procr severely compromises BM vascular integrity and function. Beyond serving as a stem cell marker, Procr also serves as a functional signaling receptor in multicellular communication. Mechanistically, Procr binds heat shock protein A8 (HSPA8) to promote Foxc2 nuclear translocation, thereby upregulating delta-like ligand 4 (Dll4) transcription to sustain Dll4/Notch3 activation in mesenchymal stem cells (MSCs), revealing a Procr/HSPA8/Foxc2/Dll4 axis essential for EC and MSC cross talk. Through the HSPA8/Foxc2/Dll4/Notch3 axis, Procr+ ECs instruct MSC notch signaling, coordinating their adipogenic and osteogenic differentiation to maintain HSC self-renewal and myeloid output. Building on this mechanism, we demonstrated conserved functionality of Procr+ endothelial progenitor cells (EPCs) in human BM. Human PROCR+ ECs were found to similarly enhance DLL4/Notch3 signaling in MSCs, consequently preserving HSC function, confirming their therapeutic relevance. Our work highlights that Procr+ EPCs sustain vascular integrity and govern MSC-dependent HSC maintenance, offering targeted clinical strategies for niche regeneration.

Li C, Wu B, Li Y, et al. Loss of sphingosine kinase 2 promotes the expansion of hematopoietic stem cells by improving their metabolic fitness. <i>Blood</i> . 2022;140(15):1686-1701.

Haploidentical transplant, gene therapy, and standard care in sickle cell disease: a cost-effectiveness analysis

Abstract Nonmyeloablative-related haploidentical allogeneic stem cell transplantation (NMAC-HID allo-HSCT) has emerged as an additional treatment to achieve durable remission in sickle cell disease (SCD), a prevalent blood disorder characterized by painful vaso-occlusive crises and chronic anemia. The standard of care (SOC) for SCD includes hydroxyurea, pain management, and blood transfusion, but patients with SCD still lose several decades of life expectancy. Gene therapy (GT) for SCD is the other treatment for lifelong disease amelioration in SCD, with accessibility limited by cost and manufacturing capacity in the United States and globally. Two recent prospective studies that evaluated NMAC-HID allo-HSCT validated haploidentical allotransplantation as an efficacious and accessible treatment option in the era of GT. Given the ongoing price negotiation across jurisdictions for GT implementation and the absence of cost-effectiveness data comparing NMAC-HID allo-HSCT and GT, we conducted a cost-effectiveness analysis of NMAC-HID allo-HSCT vs GT vs SOC for adults and children living with SCD. The primary outcomes were the incremental cost-effectiveness ratio and the net monetary benefits across these 3 strategies. The secondary outcome was the maximum cost-effective threshold price for GT compared with NMAC-HID allo-HSCT. Treatment with SOC, NMAC-HID allo-HSCT, and GT accrued 14.3, 20.1, and 22.1 quality-adjusted life-years at costs of $1.22 million, $1.15 million, and $2.75 million, respectively. NMAC-HID allo-HSCT was the cost-effective strategy compared with GT in 100% of 10 000 Monte Carlo iterations across the base case and all scenario analyses. The maximum cost-effective thresholds for GT vs SOC were $1.4 million in the United States and $4200 to $22 000 across India, Nigeria, and Tanzania, depending on willingness-to-pay thresholds.

Granulopoiesis under attack by mutant IDH1

Abro B, Maurer MJ, Habermann TM, et al. Real-world impact of differences in the WHO and ICC classifications of non-Hodgkin lymphoma: a LEO cohort study analysis. <i>Blood</i> . 2024;144(19):2063-2066.

<i>IDH2</i> clonal hematopoiesis and IKAROS loss cooperate in a B-ALL subtype after lenalidomide therapy for multiple myeloma

Abstract Lenalidomide, a maintenance treatment in multiple myeloma first-line therapy, increases the risk of secondary malignancies, including B-cell precursor acute lymphoblastic leukemia (B-ALL). We present a comprehensive molecular characterization of 57 patients with lenalidomide-associated B-ALL (LenB-ALL), revealing 3 mutational subgroups: (1) TP53mt (30%); (2) IDH2mt (p.R140Q) (23%); and (3) other, including NRAS/KRASmt. Remarkably, IDH2 R140Q mutations were highly enriched in LenB-ALL compared with those in primary B-ALL (P&amp;lt; .001). Furthermore, IKZF1 intragenic deletions, often subclonal and likely RAG recombinase-mediated, were observed in 54% (7/13) of IDH2mt patients with LenB-ALL. IDH2 mutations were not restricted to the leukemic clone: they persisted during measurable residual disease–negative remission and were identified in lymphoid as well as myeloid cell populations using fluorescence-activated cell sorting and single-cell RNA sequencing. This indicates a preleukemic origin of the IDH2 mutation within the context of clonal hematopoiesis. Transcriptomic and DNA methylation analyses revealed a distinct gene expression profile and a DNA hypermethylation phenotype in IDH2mt LenB-ALL, including IDH2mt-specific as well as lenalidomide-associated features. We propose that lenalidomide promotes the expansion of IDH2-mutated clonal hematopoiesis and, via IKAROS downregulation, induces a maturation arrest at the B-cell precursor stage. Subsequent genetic or epigenetic alterations render leukemogenesis independent of ongoing lenalidomide exposure. All these data define IDH2mt B-ALL as a distinct molecular subtype that is markedly overrepresented after lenalidomide treatment and highlight clonal hematopoiesis as a key contributing factor in the development of LenB-ALL.

Mutant IDH1 blocks neutropoiesis by repressing myeloid progenitor programs

Abstract IDH1 and IDH2 are frequently mutated in various cancers, including acute leukemias. However, the distinct mechanisms by which mutant IDH1 or IDH2 drive hematopoietic neoplasms remain poorly understood. Here, we analyzed DNA methylation in IDH1- and IDH2-mutant acute myeloid leukemia and found neutrophil lineage-specific epigenetic alterations in IDH1-mutant patients that went along with severely impaired neutrophil differentiation. Transcriptional analysis of normal hematopoiesis in humans and mice revealed a strong physiological upregulation of IDH1/Idh1 in myeloid progenitors. To study the functional effects of Idh1 mutations on hematopoiesis in a preleukemic setting, we used a genetically engineered inducible mouse model expressing a heterozygous Idh1 mutation under control of the endogenous promotor. Our study revealed a cell-intrinsic block in neutrophil differentiation caused by repression of myeloid transcription programs in neutrophil progenitors. This included impaired expression of Cebpe, which encodes a key transcription factor regulating neutrophil differentiation. Reactivation of Cebpe expression, by overexpression of its upstream regulator Cebpa or following treatment with hypomethylating agents, restored differentiation, indicating that the differentiation block is reversible. In summary, we found a reversible, preleukemic impairment of neutrophil differentiation in IDH1-mutant hematopoiesis that correlates with elevated IDH1 expression in myeloid progenitors and likely explains the strong association of IDH1 mutations with myeloid neoplasms.