Stem Cells 1
Period of duration of course
Basic knowledge of cellular and molecular biology.
Definition of stem cell; methods of division and differentiation potential; general properties of the stem niche; types of adult stem cells; the male and female germinal stem niches of drosophila; introduction to the adult neural stem niche. The embryonic neural stem cell and its lineage; radial glia and embryonic neurogenesis; positional and histological identity; corticogenesis and radial migration; nerogenetic timing of the cortical layers; embryonic neural stem niche.
Discovery and characterization of the neurogenetic properties of radial glial cells. Comparison between invertebrate neurogenesis and vertebrate neurogenesis. Description of Notch signaling in invertebrates. Lateral inhibition in invertebrates. conservation of the molecular mechanisms of lateral inhibition (proneural genes, neurogenic genes and their interaction) in vertebrates.
The adult stem cell neurogenetic niche. Brief description of the different niches. The VZ-SVZ niche as a paradigm for controlling neural stemness. the four cellular components of the niche: cells E, B, C and A. "Pinwheel" structure of the niche. Extrinsic signals and intrinsic control signals of stemness. Control of the niche by Vcam1 and by the Notch, SHH, EGF and BMP reports. Paracrine influence of neurotransmitters GABA and 5-HT, and of IL-1, on stemness
The qNSC / aNSC balance control in the adult neurogenic niche of V-SVZ (http://dx.doi.org/10.1016/j.stemcr.2016.08.016).
The role of SHH in controlling the pool of NSCs in the adult neruogenetic niche of the SGZ (DOI: https://doi.org/10.7554/eLife.42918)
The adult intestinal stem cell niche. Adult hematopoietic stem cells. Mesenchymal cells as an example of mutlipotent adult stem cells.
Mouse embryonic stem cells: ground state and primed cells, chemical niches for the maintenance of pluripotency. Differentiation of pluripotent cells in vitro mimics the early development of embryonic tissues. Role of different intracellular signaling in the differentiation of pluripotent cells towards distinct differentiation fates in vitro. Human embryonic and reprogrammed pluripotent cells, and their use for cell therapy and disease modeling. Mesoendodermal and cerebral organoids. Molecular mechanisms underlying the maintenance of ground state pluripotency: role of ERK and Wnt signaling.
Cellular reprogramming according to the "Yamanaka" protocol: role of transcription factors of pluripotency. Cellular competence in reprogramming. Chromatin properties of pluripotent cells. Hyper-transcriptional pluripotent chromatin model and differentiation by tissue-specific inhibition of transcription through epigenetic remodeling.
Role of RNA interference in the control of the expression of chromatin remodelers and modifiers essential to the transition from ground-state pluripotency to epiblast.Dual role of the SOX2 transcription factor in pluripotency and neuralization. Experimental evidence of tissue-specific SOX2 / OCT4 and SOX2 / BRN2 heteroduplex formation and their differentiated control of pluripotency and neural gene targets, respectively.
Brain in a dish: modeling the development of specific types of neurons with mEScs or hiPSCs. CNS and PNS. Discovering new signaling in a dish: Activin and Shh induce Retina and Hypothaamus, respectively. Studying the formation of cortical layerying cells in a dish. The mechanisms of cortical evolution studied in a dish: a microRNA controls the development of the Corpus Callosum.
Acquisition of basic knowledge on the molecular mechanisms of specification and differentiation of stem cells, with particular attention to neural stem cells.
Developmental Biology, Gilbert