The Allen Institute is pleased to host a reimagined, virtual Hindsight 2020 - The Allen Institute Developmental Recording Symposium. This meeting will feature the latest insights from leading researchers in the fields of cell lineage and developmental recording, chaired by Jay Shendure, M.D., Ph.D. and Michael Elowitz, Ph.D., of the Allen Discovery Center at UW Medicine.
The symposium was previously scheduled for March 3-5, 2020 at the Allen Institute in Seattle, WA. In order to accommodate the full lineup of speakers in a virtual format, the symposium will now be presented as a series of virtual events. The kickoff event will be hosted by the Allen Institute as a Zoom Webinar. Future seminars in the Hindsight 2020 Virtual Series will be hosted by the Allen Discovery Center at UW Medicine. Visit their website to learn more about the series.
See below for the agenda and speaker information for the Hindsight 2020 virtual series kick-off to be held on Wednesday, November 18.
8:30am-12:05pm Pacific Time
This symposium will be held virtually via Zoom webinar. Registered attendees will be sent the link to join in advance of the meeting.
- Allen Discovery Center at UW Medicine
- Hindsight 2020 Virtual Seminar Series
- DREAM Challenge Q&A
- DREAM Challenge Best Performers
Please contact Events@alleninstitute.org with any questions.
Event Overview (All Times Pacific)
Wednesday, November 18:
- Conference setup & login, 8:20-8:30am
- Welcome & introductions, 8:30-8:40am
- Presentations, 8:40-10:00am
- Break, 10:00-10:15am
- Presentations & DREAM Challenge Session, 10:15-11:55am
- Closing remarks, 11:55am-12:05pm
Allon Klein, Ph.D.
Harvard Medical School
"Lineage reconstruction from clonal correlations"
Abstract: To understand mechanisms of cell fate choice, a 'minimal' goal of stem cell and developmental biology is to establish the fate decisions that cells undergo, and their sequence. Differentiation is often modeled as a branching process, but cells with different developmental histories can converge onto the same mature cell identities in several tissues. How can we infer the order of fate choices, and identify convergent differentiation? Using hematopoiesis as a model system, I will present our work exploring whether stochasticity of cell fate choice during tissue development could be harnessed to infer developmental sequences using genetic lineage tracing experiments combined with single cell RNA-Seq. I will specifically address:
1. Are we measuring the state of cells sufficiently well to map the sequence of events in fate choice? In hematopoiesis, we show that fate biases depend on stable cellular properties hidden from single-cell RNA sequencing, arguing for more comprehensive descriptions of cell state.
2. Can we establish the conditions under which the final distribution of barcodes over observed cell types encodes developmental relationships? This leads us to a generalized theory of multi-type branching processes, that identifies pitfalls in analysis. We use the theory to develop a practical pipeline for clonal analysis. We detect couplings between monocytes and dendritic cells and between erythrocytes and basophils that suggest multiple pathways of differentiation for these lineages.
Bio: Throughout Dr. Allon Klein’s career, he has been interested in how cells make decisions. This is a multi-scale problem, with explanations spanning from identifying ‘molecular instabilities’ that drive regulatory networks to one of several stable states, to defining interactions across tissues and even organisms. Understanding cellular decision-making also requires determining how cells and tissues maintain discrete phenotypes over many years of life. These problems cannot be solved using any single discipline. Dr. Klein worked on these problems first as a statistical physicist in his PhD with Dr. Ben Simons (Cambridge), before transitioning into experimental biology and computational genomics during a postdoc with Dr. Marc Kirschner. To address these general questions, the Klein lab develops new assays, technologies and theoretical methods.
Cole Trapnell, Ph.D.
University of Washington
"Massively multiplex chemical transcriptomics at single cell resolution"
Abstract: High-throughput chemical screens typically employ coarse assays, e.g. cell survival, limiting what can be learned about mechanisms of action, off-target effects, and heterogeneous responses. Here we introduce sci-Plex, which uses ‘nuclear hashing’ to quantify global transcriptional responses to thousands of independent perturbations at single-cell resolution. As a proof-of-concept, we applied sci-Plex to screen 3 cancer cell lines exposed to 188 compounds. In total, we profiled ~650,000 single-cell transcriptomes across ~5,000 independent samples in one experiment. Our results reveal substantial intercellular heterogeneity in response to specific compounds, commonalities in response to families of compounds, and insight into differential properties within families. In particular, our results with HDAC inhibitors support the view that chromatin acts as an important reservoir of acetate in cancer cells.
Bio: Cole Trapnell is an Associate Professor of Genome Sciences at the University of Washington. Dr. Trapnell has formal training in both computational and experimental biology, with a broad background in functional genomics and specific training in next generation sequencing and gene expression analysis. As a graduate student with Steven Salzberg and Lior Pachter, Dr. Trapnell wrote TopHat and Cufflinks, two widely used tools for transcriptome sequencing (RNA-seq) analysis. As a postdoctoral fellow in John Rinn's lab at Harvard, Dr. Trapnell sought experimental training focused on analysis of cell differentiation, and developed “single-cell trajectory analysis”, an approach for studying cell differentiation using single-cell RNA-seq. At the University of Washington, the Trapnell lab develops single-cell genomics assays and the algorithms needed to analyze them. The lab then applies these technologies to dissect the genetic architecture that governs cell fate decisions in development, reprogramming, and disease. The Trapnell lab co-developed, along with Jay Shendure’s lab, a general, ultra-scalable workflow for single-cell genomics called “combinatorial cellular indexing”. They recently used this approach to construct a transcriptional atlas for the C. elegans nematode and profile organogenesis in the mouse at whole-embryo scale. Dr. Trapnell was the recipient of an NIH Director's New Innovator Award, an Alfred P. Sloan Fellowship, the Dale F. Frey Award, and the ISCB Overton Prize.
Barbara Treutlein, Ph.D.
"Lineage dynamics during brain organoid formation"
Abstract: Diverse regions develop within cerebral organoids generated from human induced pluripotent stem cells (iPSCs), however it has been a challenge to understand the lineage dynamics associated with brain regionalization. Here we establish an inducible lineage recording system that couples reporter barcodes, inducible CRISPR/Cas9 scarring, and single-cell transcriptomics to analyze lineage relationships during cerebral organoid development. We infer fate-mapped whole organoid phylogenies over a scarring time course, and reconstruct progenitor-neuron lineage trees within microdissected cerebral organoid regions. We observe increased fate restriction over time, and find that iPSC clones used to initiate organoids tend to accumulate in distinct brain regions. We use lineage-coupled spatial transcriptomics to resolve lineage locations as well as confirm clonal enrichment in distinctly patterned brain regions. Using long term 4-D light sheet microscopy to temporally track nuclei in developing cerebral organoids, we link brain region clone enrichment to positions in the neuroectoderm, followed by local proliferation with limited migration during neuroepithelial formation. Our data sheds light on how lineages are established during brain organoid regionalization, and our techniques can be adapted in any iPSC-derived cell culture system to dissect lineage alterations during perturbation or in patient-specific models of disease.
Bio: Barbara Treutlein performed her PhD in single-molecule biophysics at LMU Munich, Germany. During her Postdoc with Stephen Quake at Stanford University, she pioneered the use of microfluidic-based single-cell transcriptomics to dissect the cellular composition of complex tissues, and to elucidate differentiation pathways during lung development and cell reprogramming. 2015-2018, she was a Max Planck Research Group Leader at the Max Planck Institute for Evolutionary Anthropology in Leipzig and held a tenure-track assistant professorship at TU Munich. Since 2019, Barbara is Professor for Quantitative Developmental Biology at the ETH Zürich D-BSSE, Switzerland. Her group uses and develops single-cell genomics approaches in combination with stem cell based 2- and 3-dimensional culture systems to study human organogenesis. For her work, Barbara has received multiple awards including the Friedmund Neumann Prize of the Schering Foundation and the Dr. Susan Lim Award for Outstanding Young Investigator of the International Society of Stem Cell Research.