A5084004045- Retinal Development and Disorders
- Epigenetics and DNA Methylation
- Single-cell and spatial transcriptomics
- Neurogenesis and neuroplasticity mechanisms
- Developmental Biology and Gene Regulation
- Genomics and Chromatin Dynamics
- RNA Research and Splicing
- Cell Image Analysis Techniques
- Neuroscience and Neuropharmacology Research
- Cancer-related gene regulation
- Retinal Diseases and Treatments
- Neuroinflammation and Neurodegeneration Mechanisms
- Connexins and lens biology
- RNA and protein synthesis mechanisms
- Retinal Imaging and Analysis
- CRISPR and Genetic Engineering
- Molecular Biology Techniques and Applications
- Protein Degradation and Inhibitors
- Chromatin Remodeling and Cancer
- Neuroscience of respiration and sleep
- Ubiquitin and proteasome pathways
- Pluripotent Stem Cells Research
- RNA modifications and cancer
- Fibroblast Growth Factor Research
- Photochromic and Fluorescence Chemistry
University of Oslo
2022
Johns Hopkins University
2015-2019
Johns Hopkins Medicine
2016-2019
University of Milan
2010
Pediatrics and Genetics
2010
Age-related macular degeneration (AMD) is a significant cause of vision loss in the elderly. The extent to which epigenetic changes regulate AMD progression unclear. Here we globally profile chromatin accessibility using ATAC-Seq retina and retinal pigmented epithelium (RPE) from control patients. Global decreases occur RPE with early AMD, advanced disease, suggesting that dysfunction drives disease onset. Footprints photoreceptor RPE-specific transcription factors are enriched...
Analysis of gene expression in single cells allows for decomposition cellular states as low-dimensional latent spaces. However, the interpretation and validation these spaces remains a challenge. Here, we present scCoGAPS, which defines from source single-cell RNA-sequencing (scRNA-seq) dataset, projectR, evaluates independent target datasets via transfer learning. Application developing mouse retina to scRNA-Seq reveals intrinsic relationships across biological contexts assays while...
A variety of chromatin remodeling complexes are thought to orchestrate transcriptional programs that lead neuronal precursors from earliest commitment terminal differentiation. Here we show mammalian neurons have a specialized enzyme arising neurospecific splice variant LSD1/KDM1, histone lysine specific demethylase 1, whose activity on Lys4 H3 has been related gene repression. We found alternative splicing LSD1 transcript generates four full-length isoforms combinatorial retention two...
Activity-dependent changes in synaptic structure and spine morphology are required for learning memory, depend on protein translation. We show that the kinase eukaryotic elongation factor 2 (eEF2K) regulates dendritic stability by modulating activity-dependent BDNF synthesis. Specifically RNAi knockdown of eEF2K reduces inhibits expression; whereas overexpression a constitutively activated induces maturation increases expression BDNF. Furthermore, rescues reduced eEF2K. also...
Müller glia (MG) are the only glial cell type produced by neuroepithelial progenitor cells that generate vertebrate retina. MG required to maintain retinal homeostasis and support survival of neurons. Furthermore, in certain classes, function as adult stem cells, mediating regeneration response injury. However, mechanisms regulate development poorly understood because there is considerable overlap gene expression between differentiated MG. We show LIM homeodomain transcription factor Lhx2...
Müller glia are the primary glial subtype in retina and perform a wide range of physiological tasks support retinal function, but little is known about transcriptional network that maintains these cells their differentiated state. We report selective deletion LIM homeodomain transcription factor Lhx2 from mature leads to induction reactive gliosis absence injury. Furthermore, expression also down-regulated Prph2 Rd2/Rd2 animals immediately before onset gliosis. Analysis conditional knockouts...
Hypothalamic tanycytes, a radial glial-like ependymal cell population that expresses numerous genes selectively enriched in embryonic hypothalamic progenitors and adult neural stem cells, have recently been observed to serve as source of adult-born neurons the mammalian brain. The genetic mechanisms regulate specification maintenance tanycyte identity are unknown, but critical for understanding how these cells can act progenitor cells. We observe LIM (Lin-11, Isl-1, Mec-3)-homeodomain gene...
Abstract Retinal neurogenesis occurs through partially overlapping temporal windows, driven by concerted actions of transcription factors which, in turn, may contribute to the establishment divergent genetic programs developing retina coordinating variations chromatin landscapes. Here we comprehensively profile murine retinal progenitors integrating next generation sequencing methods and interrogate changes accessibility at embryonic post-natal stages. An unbiased search for motifs open...
Precise control of the relative ratio retinal neurons and glia generated during development is essential for visual function. We show that Lhx2, which encodes a LIM-homeodomain transcription factor specification differentiation Müller glia, also plays critical role in neurons. Overexpression Lhx2 with its transcriptional coactivator Ldb1, triggers cell cycle exit inhibits both Notch signaling gliogenesis. Lhx2/Ldb1 overexpression induced formation wide-field amacrine cells (wfACs). In...
Computational prediction of transcription factor (TF) binding sites in different cell types is challenging. Recent technology development allows us to determine the genome-wide chromatin accessibility various cellular and developmental contexts. The profiles provide useful information TF events physiological conditions. Furthermore, ChIP-Seq analysis was used for a range TFs multiple types. Integration these two genomic can improve events.We assessed what extent model built upon on other...
Fibroblast growth factor (FGF) signaling is an essential regulator of lens epithelial cell proliferation and survival, as well fiber differentiation. However, the identities these FGF factors, their source tissue genes that regulate synthesis are unknown. We have found Chx10-Cre;Lhx2
(Cell Systems 8, 395–411.e1–e8; May 22, 2019) In the original published version of this paper, in Quantification and Statistical Analysis section STAR Methods, under subheading “Update Steps for Atomic Prior,” step 4 contained typographical errors two expressions. The correct should read: “4. Moving a portion value single atom (xi,k,lA) to another, adjacent (xm,n,pA) so that xi,k,lA←xi,k,lA+Δx xm,n,pA←xm,n,pA−Δx where Δx∈(−xi,k,lA,xm,n,pA). Atoms may become small from exchange, but not...
ABSTRACT New approaches are urgently needed to glean biological insights from the vast amounts of single cell RNA sequencing (scRNA-Seq) data now being generated. To this end, we propose that identity should map a reduced set factors which will describe both exclusive and shared biology individual cells, dimensions contain these reflect biologically meaningful relationships across different platforms, tissues species. find robust dependent in large-scale scRNA- Seq data, developed Bayesian...
Abstract Precise control of the relative ratio retinal neurons and glia generated during development is essential for visual function. We show that Lhx2 , which encodes a LIM-homeodomain transcription factor specification differentiation Müller glia, also plays critical role in neurons. Overexpression its transcriptional coactivator Ldb1 triggers cell cycle exit inhibits both Notch signaling gliogenesis. Lhx2/Ldb1 overexpression induced formation wide-field amacrine cells (wfACs). In...
Abstract Retinal progenitor cells (RPCs) pass through multiple stages of developmental competence, where they successively acquire and lose the ability to generate individual cell subtypes. To identify transcriptional regulatory networks that control these transitions, we conducted epigenomic transcriptomic profiling early late-stage RPCs observed a developmentally dynamic landscape chromatin accessibility. Open regions showed stage-specificity, as well those shared by RPCs, were selectively...
Abstract Age-related macular degeneration (AMD) is a leading cause of blindness in the elderly. The extent to which epigenetic changes regulate AMD progression unclear. Here we globally profiled chromatin accessibility retina and retinal pigmented epithelium (RPE) from patients controls. Global decreases occurr RPE early AMD, with advanced disease, suggesting that dysfunction cells drives disease progression. Footprints photoreceptor RPE-specific transcription factors are enriched...