Bio344 Adult Neural Stem Cells PDF
Document Details
Uploaded by FormidableJadeite611
University of Zurich
Sebastian Jessberger
Tags
Summary
This document is a lecture on adult neural stem cells, presented by Sebastian Jessberger at the University of Zurich. The topics covered include the presence of 100 billion neurons, the importance of experience and learning on brain development, and the concept of neurogenesis in the adult brain.
Full Transcript
BIO344 Adult Neural Stem Cells Sebastian Jessberger Brain Research Institute University of Zurich [email protected] 100 billion neurons Each neuron with 1‘000 to 10‘000 connections All connections combined reach easily to the...
BIO344 Adult Neural Stem Cells Sebastian Jessberger Brain Research Institute University of Zurich [email protected] 100 billion neurons Each neuron with 1‘000 to 10‘000 connections All connections combined reach easily to the moon Does brain development really stop? Experience Learning Injury “Once development was ended, the fonts of growth and regeneration of the axons and dendrites dried up irrevocably. In the adult centers, the nerve paths are something fixed, and immutable: everything may die, nothing may be regenerated.” Santiago Ramon y Cajal, 1928 Early evidence for cell division in the adult brain Analysis of adult neurogenesis BrdU labeling antibody BrdU BrdU BrdU / NeuN DNA Mouse Rat Cat Birds Tree Shrew Marmoset Rhesus Human (samples from cancer patients with age from 58-72) Eriksson et al., 1998) Spalding et al., 2013 Cell Neurogenesis in the mammalian hippocampus Immature neurons (DCX+) in 68yo hippocampal dentate gyrus Denoth-Lippuner and Jessberger, 2021 Moreno-Jimenez et al., 2019 Nature Medicine Nature Rev Neurosc Terreros-Moncal et al., 2021 Science Life-long neurogenesis in the adult hippocampus in mammals incl. humans (e.g., Altman and Das, 1964 Nature; Eriksson et al., 1998 Nature Medicine; Spalding et al., 2013 Cell; Moreno-Jimenez et al., 2019 Nature Medicine Zhou et al., 2022 Nature) Involved in certain forms of learning and memory (e.g., Clelland et al., 2009 Science; Sahay et al., 2011 Nature; Deng et al., 2013 eLife) Reduced and/or altered neurogenesis in neuro-psychiatric disease (e.g., depression, ageing) (e.g., Parent et al., 1997 J Neurosc; Santarelli et al., 2003 Science; Snyder et al., 2011 Nature) Plasticity and Repair of the Mammalian Brain Experience Learning Injury Hippocampus = village of Asterix & Obelix Hippocampal neurogenesis: far away.... Cortex Corpus callosum CA1 Dentate gyrus Thy-1 YFP Using intravital imaging to follow neural stem cells Ascl1CreERT2 / tdTOMATO (Anderson et al., 2014 Neuron) Pilz, Carta et al., 2016 J Neurosc Pilz, Bottes et al., 2018 Science Constructing lineage trees of adult neural stem cells Pilz, Bottes et al., 2018 Science One mother and her daughters Things to look at: ▪ Stem cell dynamics ▪ Mode of cell division ▪ Migration and integration ▪ Functional properties (combined with GECIs) ▪ Self-renewal potential Evidence suggesting long term Urban et al., 2016 Science self-renewal Bonaguidi et al., 2011 Cell Evidence suggesting Calzolari et al., 2015 Nature Neuroscience (SVZ) rather quick depletion Encinas et al., 2011 Cell Stem Cell Depletion of Ascl1-targeted NSCs 0 0 Ascl1 clones Gli1 clones Ascl1 clones Gli1 clones (Ascl1-targeted lineages; approx. 150 clones) Ascl1CreERT2 Comparison of datasets: average clone content Neurogenic burst Lineage trees shifted to first R division Comparison of datasets: fraction of clones with different R content Lineage trees shifted to first R division Neural stem cells Proliferating progenitors NestinGFP labeled NSCs Neurons cl11 = 57 , n Gli1 = 56 n Ascl11 = 41 , n Gli1 = 37 n Rank2 = 46 n Rank2 = 43 n Ascl1: 11.85 n Rank3 = 11 n Rank3 = 18 With David Jörg and n Gli1: 24.98 Mean Ascl1: 3.640 Mean Gli1: 10.71 n Rank4 = 1 n Rank4 = 6 lue:
