2025 Hyper Recent •CC0 1.0 Universal

This work is dedicated to the public domain. No rights reserved.

Access Preprint From Server
June 6th, 2025
Version: 1
University of California, San Francisco
neuroscience
biorxiv

Regulators of Interferon-Responsive Microglia Uncovered by Genome-wide CRISPRi Screening

McQuade, A.Open in Google Scholar•Castillo, V. C.Open in Google Scholar•Hagan, V.Open in Google Scholar•Liang, W.Open in Google Scholar•Ta, T.Open in Google Scholar•Mishra, R.Open in Google Scholar•Teter, O.Open in Google Scholar•Teyssier, N.Open in Google Scholar•Leng, K.Open in Google Scholar•Kampmann, M.Open in Google Scholar

Microglia dynamically support brain homeostasis through the induction of specialized activation programs or states. One such program is the Interferon-Responsive Microglia state (IRM), which has been identified in developmental windows, aging, and disease. While the functional importance of this state is becoming increasingly clear, our understanding of the regulatory networks that govern IRM induction remain incomplete. To systematically identify genetic regulators of the IRM state, we conducted a genome-wide CRISPR interference (CRISPRi) screen in human iPSC-derived microglia (iPS-Microglia) using IFIT1 as a representative IRM marker. We identified 772 genes that modulate IRM, including canonical type I interferon signaling genes (IFNAR2, TYK2, STAT1/2, USP18) and novel regulators. We uncovered a non-canonical role for the CCR4-NOT complex subunit CNOT10 in IRM activation, independent of its traditional function. This work provides a comprehensive resource for dissecting IRM biology and highlights both established and novel targets for modulating microglial interferon signaling in health and disease.

Similar Papers

biorxiv
Sat Jun 07 2025
Neural coding of spectrotemporal modulations in the auditory cortex supports speech and music categorization
Humans effortlessly distinguish speech from music, but the neural basis of this categorization remains debated. Here, we combined intracranial recordings in humans with behavioral categorization of speech or music taken from a naturalistic movie soundtrack to test whether the encoding of spectrotemporal modulation (STM) acoustic features is sufficient to categorize the two classes. We show that pr...
Ginzburg, J.
•
Debaque, E. C.
•
Borderie, A.
•
Morillon, B.
...•
Albouy, P.
biorxiv
Sat Jun 07 2025
Exact linear theory of perturbation response in a space- and feature-dependent cortical circuit model
What are the principles that govern the responses of cortical networks to their inputs and the emergence of these responses from recurrent connectivity? Recent experiments have probed these questions by measuring cortical responses to two-photon optogenetic perturbations of single cells in the mouse primary visual cortex. A robust theoretical framework is needed to determine the implications of th...
Chau, H. Y.
•
Miller, K. D.
•
Palmigiano, A.
biorxiv
Sat Jun 07 2025
The promise and peril of comparing fluorescence lifetime in biology revealed by simulations
Signaling dynamics are crucial in biological systems, and biosensor-based real-time imaging has revolutionized their analysis. Fluorescence lifetime imaging microscopy (FLIM) excels over the widely used fluorescence intensity imaging by allowing the measurement of absolute signal levels, independent of sensor concentration. This capability enables the comparison of signaling dynamics across differ...
Ma, P.
•
Chen, P.
•
Sternson, S.
•
Chen, Y.
biorxiv
Sat Jun 07 2025
Causal Lesion Evidence for Two Motor Speech Coordination Networks in the Brain
Speech production is supported by sensory-to-motor transformations to coordinate activity of the larynx and orofacial muscles. Here, we show that lesions to left temporal lobe areas involved in pitch processing cause reduced neural responses when repeating sentences and when humming piano melodies in a dorsal portion of the left precentral gyrus linked to laryngeal motor control. In contrast, lesi...
Burns, W.
•
Strawderman, E.
•
Meyers, S. P.
•
Schmidt, T.
...•
Garcea, F. E.
biorxiv
Sat Jun 07 2025
Stress induces distinct social behavior states encoded by the ventral hippocampus
A single, acute traumatic experience can result in a host of negative impacts on behavior, such as increased violence, reduced sociability, and exaggerated fear responses. Despite the large body of research on the neurobiology of stress, we have a poor understanding of how trauma rewires social circuits in the brain. To identify how social circuits are re-organized by stress, we interrogated the r...
Sattler, K. P.
•
Conoscenti, M. A.
•
Hedges, A.
•
Ortega, J.
...•
Zelikowsky, M.
biorxiv
Sat Jun 07 2025
Frequency tagging evidence supports perceptual separation of rapid stimuli in human fetuses
In early human development, perceptual processes grow faster with maturation, as inferred using the duration of the attentional blink and multisensory integration window. The consequences of this developmental trend for sensory-cognition in fetuses are unclear: does the fetus perceive rapid stimuli as discrete events or, rather, one fused stimulus? We addressed this question using frequency taggin...
Frohlich, J.
•
Moser, J.
•
Metaxas, D.
•
Sippel, K.
...•
Preissl, H.
biorxiv
Sat Jun 07 2025
Aging modulates the effects of scene complexity on visual search and target selection in virtual environments
Processing task-relevant visual information is important for many everyday tasks. Prior work demonstrated that older adults are more susceptible to distraction by salient task-irrelevant stimuli, leading to less efficient visual search. However, these studies often used simple stimuli, and less is known about how aging influences visual attention in environments more representative of real-world c...
Lachica, I. J.
•
Kalkar, A.
•
Finley, J. M.
biorxiv
Sat Jun 07 2025
Convergent and divergent brain-cognition relationships during development revealed by cross-sectional and longitudinal analyses in the ABCD Study
How brain networks and cognition co-evolve during development remains poorly understood. Using longitudinal data collected at baseline and Year 2 from 2,949 individuals (ages 8.9-13.5) in the Adolescent Brain Cognitive Development (ABCD) study, we show that baseline resting-state functional connectivity (FC) more strongly predicts future cognitive ability than concurrent cognitive ability. Models ...
Yeo, T.
•
Xie, Y.
•
Zhang, S.
•
Orban, C.
...•
Di Martino, A.
biorxiv
Fri Jun 06 2025
Implantable CMOS Deep-Brain Fluorescence Imager with Single-Neuron Resolution
Despite the advantages of optical imaging over electrophysiology, such as cell-type specificity, its application has been limited to the investigation of shallow brain regions (< 2 mm) because of the light scattering property of brain tissue. Passive optical conduits such as graded-index lenses and waveguides have permitted access to deeper locales but with restricted resolution and field of view,...
Yilmaz, S.
•
Choi, J.
•
Uguz, I.
•
Kim, J.
...•
Shepard, K. L.
biorxiv
Fri Jun 06 2025
Neurogenesis-dependent transformation of hippocampal memory traces during systems consolidation
Memories for events (i.e., episodic memories) change qualitatively with time. Systems consolidation theories posit that organizational changes accompany qualitative shifts in memory resolution, but differ as to the locus of this reorganization. Whereas some theories favor inter-regional changes in organization (e.g., hippocampus[-&gt;]cortex; multiple trace theory), others favor intra-regional reo...
Golbabaei, A.
•
Coelho, C. A. O.
•
de Snoo, M.
•
Josselyn, S.
•
Frankland, P.