Human Pluripotent Stem Cells

Our coming to life raises two fundamental questions, how embryonic cells with extreme potency differentiate, and how they form organs. Two related questions are how tissue stem cells replenish the body throughout life and how they degenerate in disease and aging. Cell systems that exhibit stem and progenitor characteristics are platforms for understanding these processes.

Our goal is to characterize lineage-committed progenitors that emerge from human PSCs, and to discover mechanisms of termination of pluripotency and fate choices. We translate understanding of developmental progenitors and molecular control to manufacture cells for regenerative therapies.

The specific areas of research include (but are not limited to):

1. The regulation of developmental progenitor differentiation from hPSCs by genetic, epigenetic and posttranscriptional mechanisms: We target understanding gene regulatory networks that govern commitment of progenitors in conjunction to termination of the pluripotent state. For example, we have recently discovered a network of four transcription factors and epigenetic regulation that govern differentiation of trophoblast progenitors from human PSCs. Moreover, we discovered that a network of RNA binding proteins and long non-coding RNA that regulate on the post-transcriptional level the equilibrium of pluripotency and differentiation of human and mouse PSCs. Furthermore, we develop transcriptomics technologies to broaden our understanding of these processes. Finally, we derive iPSCs from diverse species for studying comparative developmental biology, evolution and endangered species conservation.

2. The mechanistic origins of congenital impairments in developmental progenitors: Derivation of iPSCs from patients is a powerful approach to model disease. Moreover, we use gene-editing technologies like CRISPR for generating iPSC disease models. Our focus is common and rare forms of neurocristopathies and neuropathologies.

3. The differentiation of organoid systems: techniques for derivation of miniature organs in culture named collectively organoids, are transforming our capabilities to understand how they form and affected by disease. We focus on developing lung and cerebral organoids.

Technologies
We use a comprehensive set of validation tools including production of genetically modified animals and CRISPR-CAS9 genetic engineering of human and animal ESCs and iPSCs. Among the cutting-edge instrumentation made available to us through the Institute for Stem Cell Research are FACSAria III sorters, flow cytometers, time lapse and confocal microscopes, DNA sequencers and more. We work closely with the Institute of Bioinformatics and Systems Biology to perform network and biomedical data analysis.