Vanessa Donega

Vanessa Donega
Amsterdam University Medical Center | VUmc · Department of Anatomy and Neurosciences

PhD

About

27
Publications
3,494
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563
Citations
Additional affiliations
January 2018 - present
University Medical Center Utrecht
Position
  • PostDoc Position
Description
  • As a Postdoctoral fellow in Hol's lab, I investigate novel therapeutic strategies to promote brain repair in degenerative brain diseases, such as Parkinson's disease.
September 2014 - January 2018
Stem Cell And Brain Research Institute
Position
  • PostDoc Position
Description
  • As a Postdoctoral fellow in Raineteau's lab, I investigate i) the competence of glutamatergic progenitors to repair injury and the use of small molecules as a therapeutic strategy to promote brain repair.
January 2010 - September 2014
University Medical Centre Utrecht
Position
  • PhD Student
Description
  • Intranasal Mesenchymal Stem Cell (MSC) treatment has been shown to improve behavior and reduce lesion size. My project focused on improving intranasal MSC treatment and clarifying the molecular and cellular mechanisms underlying neonatal brain repair.
Education
September 2007 - June 2009
Utrecht University
Field of study
  • Experimental and Clinical Neuroscience
September 2004 - June 2007
Utrecht University
Field of study
  • Biomedical Sciences

Publications

Publications (27)
Article
Full-text available
Previous work from our group has shown that intranasal MSC-treatment decreases lesion volume and improves motor and cognitive behavior after hypoxic–ischemic (HI) brain damage in neonatal mice. Our aim was to deter-mine the kinetics of MSC migration after intranasal administration, and the early effects of MSCs on neurogenic processes and gliosis a...
Article
Full-text available
There is growing evidence for a tentative cellular repair in the forebrain following perinatal injuries. In this review, we present the evidences and shortcomings in this regenerative attempt. We discuss recent progress in elucidating the origin, diversity, and competence of postnatal neural stem cells/progenitor cells. Finally, we propose new stra...
Article
Full-text available
Progenitors of cortical glutamatergic neurons (Glu progenitors) are usually thought to switch fate before birth to produce astrocytes. We used fate-mapping approaches to show that a large fraction of Glu progenitors persist in the postnatal forebrain after closure of the cortical neurogenesis period. Postnatal Glu progenitors do not accumulate duri...
Article
Full-text available
It is currently accepted that the human brain has a limited neurogenic capacity and an impaired regenerative potential. We have previously shown the existence of CD271-expressing neural stem cells (NSCs) in the subventricular zone (SVZ) of Parkinson's disease (PD) patients, which proliferate and differentiate towards neurons and glial cells in vitr...
Article
Full-text available
Following the decline of neurogenesis at birth, progenitors of the subventricular zone (SVZ) remain mostly in a quiescent state in the adult human brain. The mechanisms that regulate this quiescent state are still unclear. Here, we isolate CD271+ progenitors from the aged human SVZ for single-cell RNA sequencing analysis. Our transcriptome data rev...
Article
Full-text available
Dysregulation of microglial function contributes to Alzheimer’s disease (AD) pathogenesis. Several genetic and transcriptome studies have revealed microglia specific genetic risk factors, and changes in microglia expression profiles in AD pathogenesis, viz. the human-Alzheimer’s microglia/myeloid (HAM) profile in AD patients and the disease-associa...
Preprint
Full-text available
Following the decline of neurogenesis at birth, progenitors of the subventricular zone (SVZ) remain mostly in a quiescent state in the adult human brain. The mechanisms that regulate this quiescent state are still unclear. Here, we isolated CD271+ progenitors from the aged human SVZ for single-cell RNA sequencing analysis. Our transcriptome data re...
Article
Full-text available
Neurogenesis continues throughout adulthood in specialized regions of the brain. One of these regions is the subventricular zone. During brain development, neurogenesis is regulated by a complex interplay of intrinsic and extrinsic cues that control stem-cell survival, renewal and cell lineage specification. Cerebrospinal fluid (CSF) is an integral...
Article
Full-text available
Strategies for promoting neural regeneration are hindered by the difficulty of manipulating desired neural fates in the brain without complex genetic methods. The subventricular zone (SVZ) is the largest germinal zone of the forebrain and is responsible for the lifelong generation of interneuron subtypes and oligodendrocytes. Here, we have performe...
Data
Sub-cutaneous injections of AR-A014418 and CHIR99021 increase glutamatergic neuron and OL progenitor numbers in the early postnatal dorsal SVZ. AR-A014418, CHIR99021 or a vehicle (CTR) was injected subcutaneously during 2 days before isolation of the brain. A) qPCR analysis of the dorsal SVZ markers Tbr2 and Pax6 in the dorsal SVZ following subcuta...
Data
List of oligonucleotide Primers used. (XLSX)
Data
GSK3β inhibitors AR-A014418 and CHIR99021 successfully activate Wnt/β-catenin signaling in vitro and in vivo. A) GSK3β inhibitors (AR-A014418 and CHIR99021) activate the Wnt canonical pathway in vitro, as indicated by increased immunodetection of Ser9-GSK3β phosphorylation. Graph shows the quantification of optical density and n ≥ 75 cells analyzed...
Data
Procedure for intraventricular infusion of GSK3β inhibitors in P90 mice. A) Infusion site (red arrow), on caudal coronal section from Mouse Paxinos Atlas. Here DAPI (in red) is infused to visualize the pattern of diffusion from the cerebrospinal fluid, on a coronal section stained with Nissl. B) Note that the rostral regions of the lateral ventricl...
Data
List of dorsalizing small molecules (Associated with Table 1A). Gene lists (dNSCs/dTAPs were compared with their ventral counterparts and the P4 SVZ (see Materials and Methods) were uploaded onto www.spied.org.uk to perform the CMAP small molecule analysis. Agents with a positive correlation have the ability to promote genes associated postnatal do...
Data
Table of small molecules to promote oligodendrogenesis (Associated with Table 1C). Gene lists (isolated OL lineage cells at different stages of differentiation were compared against those of dNSCs+dTAPs (see Materials and Methods) were uploaded onto www.spied.org.uk to perform the CMAP small molecule analysis. Agents with a positive correlation hav...
Data
CMAP of “AR-A014418” induced genes (Associated with Fig 5). Uploaded gene list for generating list of drugs to perturb adult NSC signatures into postnatal NSC signatures were further analysed on the CMAP for AR-A014418 to provide a list of gene targets that are likely to be differentially affected. Also given are relative fold change intensity and...
Data
Table of ventralizing small molecules (Associated with Table 1B) . Gene lists (vNSCs/vTAPs were compared with their dorsal counterparts and the P4 adjacent SVZ tissue (see Materials and Methods) were uploaded onto www.spied.org.uk to perform the CMAP small molecule analysis. Agents with a positive correlation have the ability to promote genes assoc...
Data
CMAP of “LY-294002” induced genes (Associated with Fig 3). Uploaded gene list for generating list of drugs to perturb OLs from postnatal dNSCs/dTAPs were further analysed on the to provide a list of gene targets that are likely to be differentially affected. Also given are relative fold change intensity and p-values. (XLSX)
Data
Accompanying raw data used in the manuscript. (XLSX)
Data
LY-294004 inhibits PI3K/Akt signaling, modulates expression of transcripts, promotes specifically Olig2+ progenitors and augments myelination. . A) P9 mice were treated with 0.06 mM LY-294002 and saline/DMSO as controls and SVZ microdomains were analyzed by western blot 45 mins after infusion. Representative immunoblots and mean densitometric value...
Data
Confirmation in the decline in SVZ activity, Wnt-signaling and dorsal-derived lineages. The spatiotemporal gene expression changes in microdissected SVZ microdomains were examined by qPCR of selected genes and processed in Partek Genomics Suit 6.6 and presented as an intensity heatmap. Only transcripts that passed the criteria of p<0.05 ANOVA versu...
Data
List of small molecules to rejuvinate adult NSCs (Associated with Table 1D). Gene lists (dNSCs+vNSCs versus adult NSCs (see Materials and Methods) were uploaded onto www.spied.org.uk to perform the CMAP small molecule analysis. Agents with a positive correlation have the ability to promote genes associated with earlier NSCs, whereas those in the ne...
Article
Full-text available
For clinical translation, we assessed whether intranasal mesenchymal stem cell (MSC) treatment after hypoxia-ischemia (HI) induces neoplasia in the brain or periphery at 14 months. Furthermore, the long-term effects of MSCs on behavior and lesion size were determined. HI was induced in 9-day-old mice. Pups received an intranasal administration of 0...
Article
Full-text available
Intranasal treatment with C57BL/6 MSCs reduces lesion volume and improves motor and cognitive behavior in the neonatal hypoxic-ischemic (HI) mouse model. In this study, we investigated the potential of human MSCs (hMSCs) to treat HI brain injury in the neonatal mouse. Assessing the regenerative capacity of hMSCs is crucial for translation of our kn...
Article
Full-text available
Neurogenesis continues throughout adulthood. The neurogenic capacity of the brain increases after injury by, e.g., hypoxia-ischemia. However, it is well known that in many cases brain damage does not resolve spontaneously, indicating that the endogenous regenerative capacity of the brain is insufficient. Neonatal encephalopathy leads to high mortal...
Article
Full-text available
Mesenchymal stem cell (MSC) administration via the intranasal route could become an effective therapy to treat neonatal hypoxic-ischemic (HI) brain damage. We analyzed long-term effects of intranasal MSC treatment on lesion size, sensorimotor and cognitive behavior, and determined the therapeutic window and dose response relationships. Furthermore,...

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