Item

ITEM ACTIONS

This item is discarded!DetailsSummary

Discarded

Journal Article

Single-Cell RNA-Sequencing-Based CRISPRi Screening Resolves Molecular Drivers of Early Human Endoderm Development

MPS-Authors

/persons/resource/persons203557

Ziller, Michael J.
Dept. Translational Research in Psychiatry, Max Planck Institute of Psychiatry, Max Planck Society;
RG Genomics of Complex Diseases, Max Planck Institute of Psychiatry, Max Planck Society;

External Resource

No external resources are shared

Fulltext (restricted access)

There are currently no full texts shared for your IP range.

Fulltext (public)

There are no public fulltexts stored in PuRe

Supplementary Material (public)

There is no public supplementary material available

Citation

Genga, R. M. J., Kernfeld, E. M., Parsi, K. M., Parsons, T. J., Ziller, M. J., & Maehr, R. (2019). Single-Cell RNA-Sequencing-Based CRISPRi Screening Resolves Molecular Drivers of Early Human Endoderm Development. Cell Reports, 27(3), 708-+. doi:10.1016/j.celrep.2019.03.076.

Abstract

Studies in vertebrates have outlined conserved molecular control of definitive endoderm(END) development. However, recent work also shows that key molecular aspects of human END regulation differ even from rodents. Differentiation of human embryonic stem cells (ESCs) to END offers a tractable system to study the molecular basis of normal and defective human-specific END development. Here, we interrogated dynamics in chromatin accessibility during differentiation of ESCs to END, predicting DNA-binding proteins that may drive this cell fate transition. We then combined single-cell RNA-seq with parallel CRISPR perturbations to comprehensively define the loss-of-function phenotype of those factors in END development. Following a few candidates, we revealed distinct impairments in the differentiation trajectories for mediators of TGFb signaling and expose a role for the FOXA2 transcription factor in priming human END competence for human foregut and hepatic END specification. Together, this single-cell functional genomics study provides high-resolution insight on human END development.