Person:
Muratore, Christina

Profile Picture

Email Address

AA Acceptance Date

Birth Date

Research Projects

Organizational Units

Job Title

Last Name

Muratore

First Name

Christina

Name

Muratore, Christina
Author's Publications: search.filters.isAuthorOfPublication.8df1ca0f-89ab-456a-80f7-0120644b6918

Search Results

Now showing 1 - 3 of 3
  • Thumbnail Image
    Publication
    Cell-type Dependent Alzheimer's Disease Phenotypes: Probing the Biology of Selective Neuronal Vulnerability
    (Elsevier, 2017) Muratore, Christina; Zhou, Constance; Liao, Meichen; Fernandez, Marty; Taylor, Walter M.; Lagomarsino, Valentina N.; Pearse, Richard; Rice, Heather C.; Negri, Joseph; He, Amy; Srikanth, Priya; Callahan, Dana; Shin, Taehwan; Zhou, Monica; Bennett, David A.; Noggle, Scott; Love, J. Christopher; Selkoe, Dennis; Young-Pearse, Tracy
    Summary Alzheimer's disease (AD) induces memory and cognitive impairment in the absence of motor and sensory deficits during its early and middle course. A major unresolved question is the basis for this selective neuronal vulnerability. Aβ, which plays a central role in AD pathogenesis, is generated throughout the brain, yet some regions outside of the limbic and cerebral cortices are relatively spared from Aβ plaque deposition and synapse loss. Here, we examine neurons derived from iPSCs of patients harboring an amyloid precursor protein mutation to quantify AD-relevant phenotypes following directed differentiation to rostral fates of the brain (vulnerable) and caudal fates (relatively spared) in AD. We find that both the generation of Aβ and the responsiveness of TAU to Aβ are affected by neuronal cell type, with rostral neurons being more sensitive than caudal neurons. Thus, cell-autonomous factors may in part dictate the pattern of selective regional vulnerability in human neurons in AD.
  • Thumbnail Image
    Publication
    Comparison and Optimization of hiPSC Forebrain Cortical Differentiation Protocols
    (Public Library of Science, 2014) Muratore, Christina; Srikanth, Priya; Callahan, Dana G.; Young-Pearse, Tracy
    Several protocols have been developed for human induced pluripotent stem cell neuronal differentiation. We compare several methods for forebrain cortical neuronal differentiation by assessing cell morphology, immunostaining and gene expression. We evaluate embryoid aggregate vs. monolayer with dual SMAD inhibition differentiation protocols, manual vs. AggreWell aggregate formation, plating substrates, neural progenitor cell (NPC) isolation methods, NPC maintenance and expansion, and astrocyte co-culture. The embryoid aggregate protocol, using a Matrigel substrate, consistently generates a high yield and purity of neurons. NPC isolation by manual selection, enzymatic rosette selection, or FACS all are efficient, but exhibit some differences in resulting cell populations. Expansion of NPCs as neural aggregates yields higher cell purity than expansion in a monolayer. Finally, co-culture of iPSC-derived neurons with astrocytes increases neuronal maturity by day 40. This study directly compares commonly employed methods for neuronal differentiation of iPSCs, and can be used as a resource for choosing between various differentiation protocols.
  • Thumbnail Image
    Publication
    Shared effects of DISC1 disruption and elevated WNT signaling in human cerebral organoids
    (Nature Publishing Group UK, 2018) Srikanth, Priya; Lagomarsino, Valentina; Muratore, Christina; Ryu, Steven C.; He, Amy; Taylor, Walter M.; Zhou, Constance; Arellano, Marlise; Young-Pearse, Tracy
    The development of three-dimensional culture methods has allowed for the study of developing cortical morphology in human cells. This provides a new tool to study the neurodevelopmental consequences of disease-associated mutations. Here, we study the effects of isogenic DISC1 mutation in cerebral organoids. DISC1 has been implicated in psychiatric disease based on genetic studies, including its interruption by a balanced translocation that increases the risk of major mental illness. Isogenic wild-type and DISC1-disrupted human-induced pluripotent stem cells were used to generate cerebral organoids, which were then examined for morphology and gene expression. We show that DISC1-mutant cerebral organoids display disorganized structural morphology and impaired proliferation, which is phenocopied by WNT agonism and rescued by WNT antagonism. Furthermore, there are many shared changes in gene expression with DISC1 disruption and WNT agonism, including in neural progenitor and cell fate markers, regulators of neuronal migration, and interneuron markers. These shared gene expression changes suggest mechanisms for the observed morphologic dysregulation with DISC1 disruption and points to new avenues for future studies. The shared changes in three-dimensional cerebral organoid morphology and gene expression with DISC1 interruption and WNT agonism further strengthens the link between DISC1 mutation, abnormalities in WNT signaling, and neuropsychiatric disease.