Last talk of the #CSSingleCells23 conference:
Karin Pelka, Gladstone/UCSF
https://gladstone.org/people/karin-pelka
Spatially organized #immune hubs in #colon #cancer
#ColonCancer
#scRNAseq
https://pubmed.ncbi.nlm.nih.gov/34450029/
Then: predict cellular interaction networks via correlations of gene program activities across #tumors
anti-tumor hubs in tumors, ISGs including CXCR3 ligands, differs between tumor types (MMR+ or -)
have data from clinical trial (biopsies before and after treatment)
https://pubmed.ncbi.nlm.nih.gov/36702949/
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#tumors #scrnaseq #coloncancer #cancer #colon #immune #cssinglecells23
Now Siddharth Dey, UCSB
https://deylab.com/
Photo-sensitive barcodes combined with topologically imposed light gradients enable spatially-resolved #SingleCell #transcriptomics and #epigenomics
a new technology: scSTAMP-seq which enables use of light patterning to achieve dynamic spatial resolution
adaptation of STAMP-seq
also applying to DNA methylation
https://www.biorxiv.org/content/10.1101/2023.05.06.539708v1
#cssinglecells23 #epigenomics #Transcriptomics #SingleCell
Next is Melanie Samuel from BCM
https://thesamuellab.org/
Molecular regulation of #immune cell #plasticity and function in the #brain
"Our brain is the ultimate time machine" 🙂
How to target #synapses (for intervention) while preserving them (to avoid "turning back the clock"
Possibility that #microglia could be harnessed
partnered with IMPC (impc.org) to find microglia regulators in retina
one cool hit: SIRPα
it's NOT involved in #phagocytosis... surprise
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#cssinglecells23 #phagocytosis #Microglia #synapses #brain #plasticity #immune
First speaker of the session (Cell identity in situ)
is Elana Fertig
of Convergence Institute at Johns Hopkins
https://fertiglab.com/
She has background in weather prediction (!) ⛈️ which has convergence with predictive medicine (such as huge data sets)
Looks at #PancreaticCancer with spatial #proteomics
now #scRNAseq
Developed CoGAPS matrix factorization, can identify cell state transitions
Using PhysiCell to build models
http://physicell.org/
#cancer
#SingleCell
#CSSingleCells23
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#cssinglecells23 #SingleCell #cancer #scrnaseq #Proteomics #pancreaticcancer
Judith Zaugg from EMBL
https://www.embl.org/groups/zaugg/
How do cells integrate extrinsic signals and intrinsic state? A systems #epigenetics approach
Individual uniqueness (of people) -- molecular basis of #variation
Needed: systems epigenetics framework
signaling -- TFs -- regulatory elements -- genes
tools for inference & evaluation of enhancer-mediated gene regulatory networks called GRaNIE and GRaNPA 😃
https://www.embopress.org/doi/full/10.15252/msb.202311627
example of problem: https://www.embopress.org/doi/full/10.15252/msb.20209539
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#cssinglecells23 #variation #epigenetics
Second half of the "variation and information" session #CSSingleCells23
led off by Sam Morris of WashU
http://morrislab.wustl.edu/
Multi-omic lineage tracing: insights into reprogramming cell identity
her piece in *Development*, "The evolving concept of cell identity in the single cell era"
working on "induced hepatocytes", start with fibroblasts, via "induced endoderm progenitors"
new work on #adipocytes
https://www.biorxiv.org/content/10.1101/2023.06.01.543318v1
#reprogramming
#StemCells
#CellIdentity
#CellFate
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#cellfate #cellidentity #stemcells #reprogramming #adipocytes #cssinglecells23
Yogesh Goyal at Northwestern Feinberg
https://www.goyallab.org/
Topic:
Tracing rare cell plasticity and diverse fate decisions in single cancer cells
Begins with reference to (and pic of) Monod's *Chance and Necessity*
#CellFate
#SingleCell
#CSSingleCells23
Emphasizing non-genetic differences between cells, something we can only see at single-cell resolution
Refers to Luria & Delbruck 1943 about bacterial resistance (to phage), relevant to cancer resistance to therapy (selected)
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#cssinglecells23 #SingleCell #cellfate
Now Katie Pollard from UCSF
https://docpollard.org/
Resolving single-cell regulatory elements across species and contexts with CellWalker2
lab builds #statistical models and #ComputationalBiology tools
#neuroscience
did microdissection then single-cell ATAC-seq
developed CellWalker to solve challenges in resolving regulatory elements
https://genomebiology.biomedcentral.com/articles/10.1186/s13059-021-02279-1
#GeneExpression
#genomics
#SingleCell
#CSSingleCells23
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#cssinglecells23 #SingleCell #genomics #geneexpression #neuroscience #computationalbiology #statistical
Last speaker of the day is the keynote:
Xiaowei Zhuang
Harvard University
https://zhuang.harvard.edu/pi.html
Spatially resolved #SingleCell genomics and cell atlas of the #brain
Explaining MERFISH, now I get it 🤓
Now have adapted to #epigenome: https://pubmed.ncbi.nlm.nih.gov/36272405/
and to thick tissue:
https://www.biorxiv.org/content/10.1101/2023.07.21.550124v1
Now discussing this epic MERFISH atlas of the whole mouse brain
https://www.biorxiv.org/content/10.1101/2023.03.06.531348v1
use imputation to infer cell-cell interactions (several hundred cell types), cool
#cssinglecells23 #epigenome #brain #SingleCell
Now Neda Bagheri at U of Washington
https://www.bagherilab.com/
Emulating emergent spatio-temporal cell population dynamics with #machinelearning algorithms remains challenging
Population dynamics arise from autonomous #SingleCell decisions
e.g. in context of #cancer progression
Created tool called ARCADE = Agent-based Representation of Cells And Dynamic Environments
https://bagherilab.com/resources.php
But model is computationally expensive...
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#cssinglecells23 #systemsbiology #computationalbiology #cancer #SingleCell #machinelearning
Rong Fan at Yale
https://www.fan-lab.org/
Spatial Multi-Omics Sequencing at Cellular Level via Deterministic Barcoding in Tissue
first slide called "2006--the ice age of single-cell biology," referring to review article by Johanna Joyce
Recent great technical advance: spatial CITE-seq
https://www.nature.com/articles/s41587-023-01676-0
and spatial ATAC-seq
#cssinglecells23 #epigenetics #Transcriptomics
Aviv Regev (Genentech)
https://www.gene.com/scientists/our-scientists/aviv-regev
From cell to perturbation atlases
Deciphering causal intra- and intercellular circuits
Using Perturb-seq
https://www.biorxiv.org/content/10.1101/2023.01.23.525198v1
#SystemsBiology
#CSSingleCells23
#GeneExpression
Now want to do multiple perturbations in one cell... do effects combine? Can do this with orig Perturb-seq, then categorize interactions
But the space of interactions is far bigger than the number of cells (in universe)
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#geneexpression #cssinglecells23 #systemsbiology
first speaker of this session:
Leeat Keren, Weizmann Institute of Science
Escalating high-dimensional imaging using combinatorial multiplexing and #deeplearning
Why can't combinatorial staining approaches (used with #RNA) work with proteins?
overlapping signals cause big math problems
And... #proteins about 10,000X more abundant than RNA
idea: use structure of biological images to constrain math solutions after combinatorial staining of proteins
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#deeplearning #cssinglecells23 #proteins #rna
Third major session at Conceptual Power of Single-Cell Biology
is "Cells in context"
chaired by Melanie Samuel (BCM) and Karin Pelka (Gladstone/UCSF)
Very cool topics incoming
Sophie Dumont at UCSF
http://www.dumontlab.ucsf.edu/
#Chromosome size alters #kinetochore attachment stability and alignment order in mammalian #mitosis
Lab interested in #SelfOrganization and emergent mechanics across scales.... "biological structures build themselves" using only local cues they get global information. mitotic spindle a great example
kinetochores attach, sense tension, can make mistakes which are corrected. how does this work when chromosomes vary in size?
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#cssinglecells23 #selforganization #mitosis #kinetochore #Chromosome
Polly Fordyce at Stanford
http://www.fordycelab.com/
Question: How do #transcription factors activate transcription?
Outside the DNA binding domain of a TF, there are numerous disordered domains, including activation domains that interact with co-activators--
very little known about that
activation domains are disordered, poorly conserved, and binding to co-activators is very low affinity
developed a #microfluidic platform to measure, tech called STAMMP
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#cssinglecells23 #microfluidic #transcription
Second half of morning session on Emerging concepts in gene regulation** **kicks off with
Songpeng Zu, UCSD
https://beyondpie.github.io/
Comprehensive single-cell analysis of chromatin accessibility in the adult mouse #brain
117 dissections (!) across whole mouse brain, using SnapATAC2
Putting data on CATlas (catlas.org)
https://www.biorxiv.org/content/10.1101/2023.04.16.536509v1
#SingleCell
#chromatin
#epigenomics
#neuroscience
#CSSingleCells23
#cssinglecells23 #neuroscience #epigenomics #chromatin #SingleCell #brain
Loic Binan of the Broad:
All-optical genetic screens of intracellular and intercellular #transcriptional circuits with Perturb-FISH
Various CRISPR-based methods to look (multiplexed) at outcomes after knockdown to explore gene expression circuits, those are great, but want richer data (morphology etc)
one guide per cell (knock down one gene per cell) see #transcriptome via MERFISH, then identify the perturbed gene via in situ T7 transcription (same chemistry as MERFISH)
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#cssinglecells23 #transcriptome #transcriptional
Now Aki Minoda, Radboud University, The Netherlands
https://www.ru.nl/en/departments/radboud-institute-for-molecular-life-sciences-fnwi-deel/cell-biology
talking about
the Mukin Mouse Ageing Atlas
(mukin means #germ-free in Japanese)
#SingleCell from tissues sampled at 2 and 19 months in mice, then #omics including #lipidomics
Looking at influence of #microbiota on changes in #aging e.g. expansion of #immune cell types, aka #inflammaging
#cssinglecells23 #inflammaging #immune #aging #microbiota #lipidomics #omics #SingleCell #germ