#cssinglecells23 — Public Fediverse posts

Last talk of the #CSSingleCells23 conference:
Karin Pelka, Gladstone/UCSF
https://pelkalab.org/

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/

1/2

Last talk of the #CSSingleCells23 conference:
Karin Pelka, Gladstone/UCSF
https://pelkalab.org/

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/

1/2

Last session of the conference! Continuing theme of "Cell identity in situ"

Parker Côté, DFCI
in Li Lab
https://ki.mit.edu/people/clinical-investigators-research-fellows/hojun-li

The #transcriptional dynamics of human #hematopoiesis at #SingleCell resolution

do #StemCells and #ProgenitorCells in #hematopoietic system (#HSPC) change with age?

HSPCs exist on a continuum of cell types

They identified #GeneExpression programs active in uncommitted cells, looking across human development (fetal to aged)

https://www.biorxiv.org/content/10.1101/2021.08.25.457678v1

#CSSingleCells23

Last session of the conference! Continuing theme of "Cell identity in situ"

Parker Côté, DFCI
in Li Lab
https://ki.mit.edu/people/clinical-investigators-research-fellows/hojun-li

The #transcriptional dynamics of human #hematopoiesis at #SingleCell resolution

do #StemCells and #ProgenitorCells in #hematopoietic system (#HSPC) change with age?

HSPCs exist on a continuum of cell types

They identified #GeneExpression programs active in uncommitted cells, looking across human development (fetal to aged)

https://www.biorxiv.org/content/10.1101/2021.08.25.457678v1

#CSSingleCells23

Last session of the conference! Continuing theme of "Cell identity in situ"

Parker Côté, DFCI
in Li Lab
https://ki.mit.edu/people/clinical-investigators-research-fellows/hojun-li

The #transcriptional dynamics of human #hematopoiesis at #SingleCell resolution

do #StemCells and #ProgenitorCells in #hematopoietic system (#HSPC) change with age?

HSPCs exist on a continuum of cell types

They identified #GeneExpression programs active in uncommitted cells, looking across human development (fetal to aged)

https://www.biorxiv.org/content/10.1101/2021.08.25.457678v1

#CSSingleCells23

Last session of the conference! Continuing theme of "Cell identity in situ"

Parker Côté, DFCI
in Li Lab
https://ki.mit.edu/people/clinical-investigators-research-fellows/hojun-li

The #transcriptional dynamics of human #hematopoiesis at #SingleCell resolution

do #StemCells and #ProgenitorCells in #hematopoietic system (#HSPC) change with age?

HSPCs exist on a continuum of cell types

They identified #GeneExpression programs active in uncommitted cells, looking across human development (fetal to aged)

https://www.biorxiv.org/content/10.1101/2021.08.25.457678v1

#CSSingleCells23

Last session of the conference! Continuing theme of "Cell identity in situ"

Parker Côté, DFCI
in Li Lab
https://ki.mit.edu/people/clinical-investigators-research-fellows/hojun-li

The #transcriptional dynamics of human #hematopoiesis at #SingleCell resolution

do #StemCells and #ProgenitorCells in #hematopoietic system (#HSPC) change with age?

HSPCs exist on a continuum of cell types

They identified #GeneExpression programs active in uncommitted cells, looking across human development (fetal to aged)

https://www.biorxiv.org/content/10.1101/2021.08.25.457678v1

#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

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

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

#CSSingleCells23

1/2

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

#CSSingleCells23

1/2

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

1/2

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

1/2

Final session of the great conference is

Cell identity in situ

#CSSingleCells23

Final session of the great conference is

Cell identity in situ

#CSSingleCells23

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

#CSSingleCells23

1/2

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

#CSSingleCells23

1/2

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

1/2

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

1/2

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)

1/2

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)

1/2

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

1/2

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

1/2

First speaker: Jingyi Jessica Li, UCLA
http://jsb.ucla.edu/

Enhancing #statistical rigor in single-cell data analysis using synthetic negative controls

"In #genomics, the negative control is often not so obvious"

How to choose null hypothesis? question is often "too abstract for biologists" 🤓

Now discussing (infamous) problems with dubious use of t-SNE

developed tool called scDEED
https://www.biorxiv.org/content/10.1101/2023.04.21.537839v1

#CSSingleCells23
#ComputationalBiology
#statistics

1/2

First speaker: Jingyi Jessica Li, UCLA
http://jsb.ucla.edu/

Enhancing #statistical rigor in single-cell data analysis using synthetic negative controls

"In #genomics, the negative control is often not so obvious"

How to choose null hypothesis? question is often "too abstract for biologists" 🤓

Now discussing (infamous) problems with dubious use of t-SNE

developed tool called scDEED
https://www.biorxiv.org/content/10.1101/2023.04.21.537839v1

#CSSingleCells23
#ComputationalBiology
#statistics

1/2

First session of the last day at this great conference,
Conceptual power of single cell biology
https://www.cell-symposia.com/conceptual-single-cells-2023/

The session is "Variation and information"
#CSSingleCells23

#BiologicalInformation

First session of the last day at this great conference,
Conceptual power of single cell biology
https://www.cell-symposia.com/conceptual-single-cells-2023/

The session is "Variation and information"
#CSSingleCells23

#BiologicalInformation

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

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

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...
1/2

#ComputationalBiology
#SystemsBiology
#CSSingleCells23

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...
1/2

#ComputationalBiology
#SystemsBiology
#CSSingleCells23

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

#Transcriptomics
#Epigenetics
#CSSingleCells23

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

#Transcriptomics
#Epigenetics
#CSSingleCells23

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)

1/2

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)

1/2

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

#CSSingleCells23

1/2

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

#CSSingleCells23

1/2

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

#CSSingleCells23

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

#CSSingleCells23

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?

#CSSingleCells23

1/2

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?

#CSSingleCells23

1/2

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?

#CSSingleCells23

1/2

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?

#CSSingleCells23

1/2

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?

#CSSingleCells23

1/2

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

#CSSingleCells23

1/2

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

#CSSingleCells23

1/2

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

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

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)

#CSSingleCells23

1/2

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)

#CSSingleCells23

1/2