A5041519692- Pluripotent Stem Cells Research
- Neurogenesis and neuroplasticity mechanisms
- Single-cell and spatial transcriptomics
- Microtubule and mitosis dynamics
- Genetic Neurodegenerative Diseases
- MicroRNA in disease regulation
- CRISPR and Genetic Engineering
- Epigenetics and DNA Methylation
- 3D Modeling in Geospatial Applications
- 3D Printing in Biomedical Research
- Cancer-related molecular mechanisms research
- Neurological disorders and treatments
- Renal and related cancers
- Human Motion and Animation
- Planarian Biology and Electrostimulation
- RNA Research and Splicing
- Genetics and Neurodevelopmental Disorders
- Cell Image Analysis Techniques
- 3D Surveying and Cultural Heritage
- Developmental Biology and Gene Regulation
University of Milan
2017-2024
Istituto Nazionale Genetica Molecolare
2017-2024
Outer radial glia (oRG) emerge as cortical progenitor cells that support the development of an enlarged outer subventricular zone (oSVZ) and expansion neocortex. The in vitro generation oRG is essential to investigate underlying mechanisms human neocortical expansion. By activating STAT3 signaling pathway using leukemia inhibitory factor (LIF), which not expressed guided organoids, we define a organoid differentiation method from pluripotent stem (hPSCs) recapitulates pool into oSVZ. oSVZ...
Deciphering how the human striatum develops is necessary for understanding diseases that affect this region. To decode transcriptional modules regulate structure during development, we compiled a catalog of 1116 long intergenic noncoding RNAs (lincRNAs) identified de novo and then profiled 96,789 single cells from early fetal striatum. We found D1 D2 medium spiny neurons (D1- D2-MSNs) arise common progenitor lineage commitment established postmitotic transition, across pre-MSN phase exhibits...
Significance We established human embryonic stem (hES) cell-inducible lines to express specific transcription factors [GS Homeobox 2 (Gsx2) and Early B-cell factor 1 (Ebf1)] improve medium spiny neuron (MSN) differentiation study striatal development in vitro. also used a nonintegrating system, by utilizing modified mRNAs transiently overexpress Gsx2 Ebf1 different hES cell line. These data can help the protocols that aim produce high-quality preparation suitable for transplantation animal...
Huntington's disease (HD) causes selective degeneration of striatal and cortical neurons, resulting in cell mosaicism coexisting still functional dysfunctional cells. The impact non-cell autonomous mechanisms between these cellular states is poorly understood. Here we generated telencephalic organoids with healthy or HD cells, grown separately as mosaics the two genotypes. Single-cell RNA sequencing revealed neurodevelopmental abnormalities ventral fate acquisition organoids, confirmed by...
Stem cell engineering of striatal medium spiny neurons (MSNs) is a promising strategy to understand diseases affecting the striatum and for cell-replacement therapies in different neurological diseases. Protocols generate cells from human pluripotent stem (PSCs) are scarce how well they recapitulate endogenous fetal remains poorly understood. We have developed protocol that modulates seeding density exposure specific morphogens generates authentic functional D1- D2-MSNs with high degree...
WDR62 is a spindle pole-associated scaffold protein with pleiotropic functions. Recessive mutations in cause structural brain abnormalities and account for the second most common of autosomal recessive primary microcephaly (MCPH), indicating as critical hub human development. Here, we investigated function corticogenesis through analysis C-terminal truncating mutation (D955AfsX112). Using induced Pluripotent Stem Cells (iPSCs) obtained from patient his unaffected parent, well isogenic...
In vitro models of corticogenesis from pluripotent stem cells (PSCs) have greatly improved our understanding human brain development and disease. Among these, 3D cortical organoid systems are able to recapitulate some aspects in vivo cytoarchitecture the developing cortex. Here, we tested three protocols for regional identity, cell type specificity neuronal maturation. Overall, all gave rise organoids that displayed a time-dependent expression maturation genes such as those involved...
RUES2 cell lines represent the first collection of isogenic human embryonic stem cells (hESCs) carrying different pathological CAG lengths in HTT gene. However, their neuronal differentiation potential has yet to be thoroughly evaluated. Here, we report that during ventral telencephalic is biased towards medial ganglionic eminence (MGE). We also show HD-RUES2 exhibit an altered MGE transcriptional signature addition recapitulating known HD phenotypes, with reduced expression...
Mammalian outer radial glia (oRG) emerge as cortical progenitor cells that directly support the development of an enlarged subventricular zone (oSVZ) and, in turn, expansion neocortex. The
GSX2 is a homeobox transcription factor (TF) controlling the specification of ventral lateral ganglionic eminence and its major derivative, corpus striatum. Medium spiny neurons (MSNs) represent largest cell component striatum they are primarily affected in Huntington disease (HD). Here, we used CRISPR technology to generate pluripotent GSX2-reporter human embryonic stem (hESC) line that can be leveraged monitor striatal differentiation real-time enrich for MSN-committed progenitors.
In vitro models of corticogenesis using mouse and human embryonic stem cells (ESC) have revolutionized improved our understanding brain development disease. Among these, 3D organoid systems were able to recapitulate features the in vivo developing cortex.Here we tested several for cell identity, heterogeneity, polarity, neuronal maturation following either default differentiation or directed conditions. Our findings support that cortical based on “intrinsic” conditions generate a broad...
ABSTRACT In vitro models of corticogenesis using mouse and human pluripotent stem cells (PSC) have greatly improved our understanding brain development disease. Among these, 3D cortical organoid systems are able to recapitulate some aspects in vivo cytoarchitecture the developing cortex. Here, we tested three protocols for regional identity, cell type-specificity neuronal maturation. Overall all gave rise organoids that displayed a time-dependent expression maturation genes such as those...
Abstract WDR62 is a spindle pole-associated scaffold protein with pleiotropic functions during corticogenesis. Recessive mutations in are associated structural brain abnormalities and account for the second most common cause of autosomal recessive primary microcephaly (MCPH), indicating as critical hub human development. Here, we investigated C-terminal truncating mutation (D955AfsX112) using induced pluripotent stem cells (iPSCs) obtained from patient MCPH2. We generated neuroepithelial...