Spatial transcriptomics/genomics with subcellular resolution
Bintu Lab
bbintu@health.ucsd.edu
Cellular and Molecular Medicine
Bioengineering
Microfluidics
Microscope lasers
Spatial transcriptomics (Method of the year in 2020 - Nature methods)
sample
5 fluorescent colors > 1,000-10,000 effective colors
Multiplex Error Robust In Situ Hybridization (MERFISH)
Chen et al Science 2015
X. Zhuang, Nature Methods, 2021
Advances in DNA synthesis (labelling thousands of molecular types)
Combinatorial encoding and decoding scheme
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MERFISH - Bintu lab applications
Imaging chromatin regulation at the genome scale
Su,...,Bintu*,Zhuang* Cell 2020
Inducing neurogenesis
Collaboration with Don Cleveland
The regulation of transcription factors across development
Collaboration with Chris Glass
Olfactory epithelium(nose)
Olfactory bulb (brain)
Receptor
RNA
Epithelium
Glomeruli
dying
convert
Inducing neurogenesis
In the adult centers, the neural paths are something fixed and immutable:
everything may die, nothing may be regenerated
Ramon y Cajal, 1928
Approaches to glia-to-neuron transdifferentiation
A therapeutically viable approach
MERFISH in the mouse brain
Astrocytes
Cortical excitatory neurons
Cortical inhibitory neurons
CA2
CA1
Oligodendrocytes
DG
Pericytes
CA3
Endothelial
Thalamic neurons
MERFISH (230 genes)
Single-cell UMAP (~57,000 cells)
Ependymal cells
Immature SVZ neurons
Mature Dentate gyrus neurons
Astrocytes
Immature dentate gyrus neurons
Zhao, Deng, Gage, Cell, 2008
SGZ
Neurogenesis within the young mouse brain
Ependymal (Progenitors)
Immature neurons
Dentate gyrus neurons
Astrocytes
8 week (young) mouse
Immature neurons
Immature
neurons
1 year (old) mouse
1 year mouse - PTBP1 ASO
Ependymal (Progenitors)
Astrocytes
Dentate gyrus neurons
Neurogenesis stops in the aged brain
Progenitors
Immature neurons
Dentate gyrus neurons
Astrocytes
8 week mouse
Immature
neurons
1 year mouse + PTBP-ASO
Neurogenesis is reinduced in the aged brain upon PTBP suppression
Collaborators
Don Cleveland
Roy Maimon
Carlos Marinas
Quan Zhu