“CHARTING THE MAMMALIAN CHROMATIN LANDSCAPE:
FROM MIXED POPULATIONS TO SINGLE CELLS”
Abstract:
Cells of identical genetic background are capable of maintaining dramatically different transcriptional programs that lead to diverse phenotypes. This variety largely depends on the cells’ distinct epigenetic states that are mostly determined by chromatin regulators (CR). Therefore, interrogating CR function and their interplay with histone marks is essential for understanding mechanisms of gene regulation and biological processes such as differentiation and cancer. Genome wide maps of chromatin collected by ChIP-seq therefore provide an extraordinary opportunity to dissect the molecular programs that govern cell states. In the first part of my talk I will describe a systematic approach that I developed for profiling a large compendium of CRs and discuss some of the underlying biology that revolves around their modular associations. Typical analysis of chromatin-state is being done on bulk populations and thus reads out an average signal over numerous numbers of cells. In some cases, the cell population of interest can be heterogeneous (e.g., in cancer), however this will be missed. In the second part of my talk I will present an innovative single cell ChIP-seq microfluidic technology, which can be used to infer sub-populations of cells based on their distinct histone modification profiles. Leveraging our novel technology, we were able to uncover two main subpopulations of embryonic stem cells, mainly, one group which is enriched for active histone mark over pluripotent related loci and a second which exhibit chromatin organization associated with early differentiation. Altogether, this technology holds a great potential to tease out novel aspects of chromatin based regulation.
