Biology subjects

Knaack, S. A.

Publications and source records attributed to Knaack, S. A..

7 recordsLinked to original sources

bioRxiv2026

Opposing Experiences Shape Parvalbumin Interneuron Plasticity through Distinct Molecular Programs

Life experiences profoundly influence brain function, yet how opposing experiences are encoded remains unclear. Here, we show that opposing experiences, chronic stress (CS) and voluntary running (VR), induce largely distinct molecular programs rather than a simple bidirectional modulation of a shared molecular program in parvalbumin interneurons (PVIs). PVI-specific translational profiling across frontal cortex and dorsal and ventral hippocampus reveals that experience-dependent gene expression is organized into brain region-specific architectures, which are further structured into distinct co-expression modules. We uncovered CS-induced upregulation of histone acetyltransferase KAT6A and H3K23 acetylation specifically in PVIs of the frontal cortex accompanied by altered genome-wide redistribution of acetylated H3K23, including genes implicated in neuropsychiatric disorders. Targeted elevation of KAT6A in PVIs recapitulates CS-induced morphological and behavioral alterations. Together, our findings reveal that opposing experiences engage distinct and region-specific molecular programs in PVIs and identify a stress-responsive epigenetic pathway underlying inhibitory circuit plasticity.

neuroscience↗

bioRxiv2025

Molecular and cellular processes disrupted in the early postnatal Down syndrome prefrontal cortex

Down syndrome is the most common genetic cause of intellectual disability and is characterized by early-onset delays in motor, cognitive, and language development. The molecular mechanisms underlying these neurodevelopmental impairments remain poorly understood. Here, we utilized single-nucleus multiomic sequencing to simultaneously profile gene expression and chromatin accessibility in the Down syndrome prefrontal cortex during early postnatal development, a critical period for synaptogenesis, neural maturation, and developmental neuroimmune interactions. Our findings reveal widespread dysregulation of chromatin accessibility and gene expression, with deficits spanning metabolic and synaptic pathways, oligodendrocyte lineage progression, and a pronounced neuroinflammatory signature. We present a molecular atlas of Down syndrome neuropathology at a critical stage of brain development, highlighting convergent neurodevelopmental and neurodegenerative pathways and informing potential targeted therapies for Down syndrome-associated neuroinflammation.

neuroscience↗

bioRxiv2023

The Single-Cell Transcriptome Program of Nodule Development Cellular Lineages in Medicago truncatula

Legumes can establish a symbiotic relationship with nitrogen-fixing rhizobia by developing nodules after root exposure to lipo-chito-oligosaccharides secreted by the bacteria. Nodule development initiates with anticlinal mitotic divisions in the pericycle and endodermal and inner cortical cells, establishing cell lineages that ultimately form each nodule compartment. We characterized these lineages by isolating and sequencing the transcriptome of Medicago truncatula single nuclei derived from uninoculated roots and roots undergoing early nodule development at 24, 48, and 96 hours after inoculation. To enrich samples for cells responding to the rhizobia, we complemented the analysis of the Medicago wild-type genotype A17 with a mutant for the autoregulation of nodulation, sunn-4. Analysis of cell lineage trajectories derived from the cortex indicates that their transcriptome is initially enriched for cytokinin perception and signaling while repressing auxin accumulation. As these cells differentiate to form nodules, expression of genes related to auxin biosynthesis, transport, and signaling was enhanced, while genes involved in cytokinin degradation were activated as lineages bifurcated to form the nodule meristem and infection zones. While the contribution of auxin and cytokinin in nodule development has been recognized, this single-cell resource quantifies the expression of each of their regulators, receptors and targets as cells divide and differentiate to form each nodule compartment.

plant biology↗

bioRxiv2021

Single-cell analysis resolves the genetic program of primary vascular system formation in hybrid poplar

Despite the enormous potential of novel approaches to explore gene expression at a single-cell level, we lack a high-resolution and cell type-specific gene expression map of the shoot apex in woody perennials. We use single-nuclei RNA sequencing to determine the cell type-specific transcriptome of the Populus vegetative shoot apex. We identified highly heterogeneous cell populations clustered into seven broad groups represented by 18 transcriptionally distinct cell clusters. Next, we established the developmental trajectories of epidermal cells, leaf mesophyll, and vascular tissue. Motivated by the high similarities between Populus and Arabidopsis cell population in the vegetative apex, we created and applied a pipeline for interspecific single-cell expression data integration. We contrasted the developmental trajectories of primary phloem and xylem formation in both species, establishing the first comparison of primary vascular development between a model annual herbaceous and a woody perennial plant species. Our results offer a valuable resource for investigating the basic principles underlying cell division and differentiation conserved between herbaceous and perennial species, which also allows the evaluation of the divergencies at single-cell resolution. One Sentence SummarySingle-cell RNA-seq of the vegetative shoot apex resolved the genetic program of primary vascular development in hybrid poplar.

plant biology↗

bioRxiv2021

Temporal change in chromatin accessibility predicts regulators of nodulation in Medicago truncatula

Rhizobia can establish symbiotic associations with legumes to provide plants with nitrogen needed in agricultural systems. Symbiosis triggers extensive genome and transcriptome remodeling in the plant, yet the extent of chromatin changes and impact on gene expression is unknown. We profiled the temporal chromatin accessibility (ATAC-seq) and transcriptome (RNA-seq) dynamics of M. truncatula roots treated with rhizobia lipo-chitooligosaccharides. Using a novel approach, Dynamic Regulatory Module Networks, we predicted gene expression as a function of chromatin accessibility and accessible cis-regulatory elements. This approach identified the cis-regulatory elements and associated transcription factors that most significantly contribute to transcriptomic changes triggered by lipo-chitooligosaccharides. Regulators involved in auxin (IAA4-5,SHY2), ethylene (EIN3, ERF1) and abscisic acid (ABI5) hormone response, as well as histone and DNA methylation (IBM1), emerged among those most predictive of transcriptome dynamics. RNAi-based knockdown of EIN3 and ERF1 reduced nodule number in M. truncatula validating the role of these predicted regulators in symbiosis between legumes and rhizobia. Significance StatementLegumes can fix nitrogen through symbiosis with rhizobia in root nodules, a critical mutualistic relationship for crop productivity and agricultural sustainability. Introducing this symbiotic relationship into non-legume crops is of great interest, but limited knowledge of host genome modifications induced by rhizobia has hampered such efforts. We applied time-course analysis of chromatin accessibility and gene expression of M. truncatula roots treated with rhizobia lipochitooligosaccharides. We show that extensive remodeling of genome accessibility drives a large component of the temporal transcriptome dynamics. By predicting gene expression as a function of accessibility of regulatory features, we identified known and novel regulators that are associated with early nodule development, which may be critical for its engineering into crops.

plant biology↗

bioRxiv2021

Functional and comparative genomics reveals conserved noncoding sequences in the nitrogen-fixing clade

Nitrogen is one of the most inaccessible plant nutrients, but certain species have overcome this limitation by establishing symbiotic interactions with nitrogen-fixing bacteria in the root nodule. This root nodule symbiosis (RNS) is restricted to species within a single clade of angiosperms, suggesting a critical evolutionary event at the base of this clade, which has not yet been determined. While genes implicated in the RNS are present in most plant species (nodulating or not), gene sequence conservation alone does not imply functional conservation - developmental or phenotypic differences can arise from variation in the regulation of transcription. To identify putative regulatory sequences implicated in the evolution of RNS, we aligned the genomes of 25 species capable of nodulation. We detected 3,091 conserved noncoding sequences (CNS) in the nitrogen-fixing clade that are absent from outgroup species. Functional analysis revealed that chromatin accessibility of 452 CNS significantly correlates with the differential regulation of genes responding to lipo-chitooligosaccharides in Medicago truncatula. These included 38 CNS in proximity to 19 known genes involved in RNS. Five such regions are upstream of MtCRE1, Cytokinin Response Element 1, required to activate a suite of downstream transcription factors necessary for nodulation in M. truncatula. Genetic complementation of a Mtcre1 mutant showed a significant association between nodulation and the presence of these CNS, when they are driving the expression of a functional copy of MtCRE1. Conserved noncoding sequences, therefore, may be required for the regulation of genes controlling the root nodule symbiosis in M. truncatula.

plant biology↗

bioRxiv2018

Evolution of regulatory networks controlling adaptive traits in cichlids

Seminal studies of vertebrate protein evolution speculated that gene regulatory changes can drive anatomical innovations. However, very little is still known about gene regulatory network (GRN) evolution associated with phenotypic effect across ecologically-diverse species. Using a novel approach to reconstruct GRNs in vertebrate species, we aimed to study GRN evolution in representative species of the most striking example of an adaptive radiation, the East African cichlids. We previously demonstrated how the explosive phenotypic diversification of East African cichlids is attributed to diverse molecular mechanisms, including accelerated regulatory sequence evolution and gene expression divergence. To investigate these mechanisms across species at a genome-wide scale, our novel network-based approach identifies ancestral and extant gene co-expression modules along a phylogeny, and by integrating associated regulators, predicts candidate regulatory regions implicated in traits under selection in cichlids. As a case study, we present data from a well-studied adaptive trait - the visual system - for which we report striking cases of network rewiring for visual opsin genes, identify discrete regulatory variants, and investigate the plausibility of their association with cichlid visual system evolution. In regulatory regions of visual opsin genes, in vitro assays confirm that transcription factor binding site mutations disrupt regulatory edges across species, and segregate according to lake species phylogeny and ecology, suggesting GRN rewiring in radiating cichlids. Our approach revealed numerous novel potential candidate regulatory regions across cichlid genomes with no prior association, as well as those with previously reported associations to known adaptive evolutionary traits, thus providing proof of concept.

evolutionary biology↗