Congrats to Sisi Chen, Paul Rivaud, Jeff Park, Tiffany Tsou, and Matt Thomson for their new paper titled: Dissecting heterogeneous cell populations across drug and disease conditions with PopAlign, just published in PNAS.
This paper describes a computational framework in which we use probabilistic models to represent population data from single-cell samples, and use the models to compare samples at multiple levels: gene, cell-state, and whole population. The probabilistic models unlock a host of statistical metrics that allow us to statistically ‘align’ subpopulations across samples, and tag them for downstream comparison. What’s cool about the method is that the models compress the data by 50-100x, so we can compute across hundreds of samples without running into limitations in memory or compute resources.
The code can be found at https://github.com/thomsonlab/popalign, and new tutorials are in the works.
Congrats to Allan and the rest of the team from the Oka Lab for their latest paper titled: “The cellular basis of distinct thirst modalities”
This is a beautiful paper describing how cellular subtypes that give rise to distinct types of thirst: osmotic thirst (driving animals to drink pure water) and hypervolemic thirst (driving animals to consume both water and minerals (salts) to recover blood volume) They even show through optogenetic cell stimulation that by stimulating the neurons associated with each thirst type, they can drive specific thirst behaviors. Very cool!
Designing signaling environments to steer transcriptional diversity in neural progenitor cell populations
Jong H. Park, Tiffany Tsou, Paul Rivaud, Matt Thomson, Sisi Chen
Stem cell populations within developing embryos are diverse, composed of many different sub-populations of cells with varying developmental potential. The structure of stem cell populations in cell culture remains poorly understood and presents a barrier to differentiating stem cells for therapeutic applications. In this paper we develop a framework for controlling the architecture of stem cell populations in cell culture using high-throughput single cell mRNA-seq and computational analysis. We find that the transcriptional diversity of neural stem cell populations collapses in cell culture. Cell populations are depleted of committed neuron progenitor cells and become dominated by a single pre-astrocytic cell population. By analyzing the response of neural stem cell populations to forty distinct signaling conditions, we demonstrate that signaling environments can restructure cell populations by modulating the relative abundance of pre-astrocyte and pre-neuron subpopulations according to a simple linear code. One specific combination of BMP4, EGF, and FGF2 ligands switches the default population balance such that 70% of cells correspond to the committed neurons. Our work demonstrates that single-cell RNA-seq can be applied to modulate the diversity of in vitro stem cell populations providing a new strategy for population-level stem cell control.
Lior Pachter (BS ’94), Matt Thomson, and David Van Valen (PhD ’11) all recently joined Caltech’s faculty as part of an Institute initiative to focus attention on computational biology. Caltech magazine sat down with them to discuss the ongoing biological data explosion and its harmonious relationship with computational tools as well as how these intersecting revolutions will change the future of privacy, ethics, and what it means to be human.
When: Tue 7/30, 1PM
Where: Kerckhoff 101.
Adrian Bruckner will be speaking on beetles, and also the interesting challenges around genome/transcriptome assembly and alignment for new organisms.
Single-cell biology as a tool to reveal the evolutionary assembly of a rove beetle chemical defense system
Adrian Brückner (Postdoc, Parker lab)
Across the Metazoa, the emergence of new modes of ecological interaction has been enabled by the repeated evolution of exocrine glands. Unique glands, bestowed with the capacity to synthesize and secrete specialized compounds, have evolved convergently and with great frequency in virtually all animal phyla. Glandular novelties arise even in single genera or species, in each case modifying how animals interact with their environment through trophic resource exploitation, pheromonal communication, chemical defense and parental care. We proposed to use a new model system – the rove beetle Dalotia coriaria – to understand how this paradigm – glands in animal – emerged from the combined action of constituent cells and how they emergent functionality evolved from the assembly of novel cell types on a molecular level.
For the seminar, I will i) shortly introduce you to our model system and the chemical ecology of predator-prey interactions, ii) share our biochemical and first single cell RNAseq results, iii) talk about the power of scRNAseq for evolutionary analyses and iv) discuss with you the challenges and caveats of scRNAseq in newly establish model organisms.