Reading and writing cell histories: New genomic technologies to unlock cell programming

In 2006, a team of scientists figured out how to “reprogram” mature human skin cells to revert them back to an earlier stage of development, generating what are known as induced pluripotent stem cells, a general-purpose kind of cell that can — in theory — develop into any other type of human cell. In the ensuing years, researchers have worked to spur these pluripotent stem cells to develop into healthy heart, brain, intestine or other types of human cells, with the hope of eventually generating stem cell therapies that could repair or replace diseased organs. Unfortunately, many of these efforts have run into stumbling blocks: The resulting cells aren’t mature, don’t work as they should, or grow into mixtures of different types of cells. Samantha Morris has developed new technologies capable of recording cells’ molecular histories as they develop. She will lead a team working to create a “blueprint” of cell identity that will enable any researcher in the world to improve the way they generate specific kinds of cells from pluripotent stem cells, with the ultimate goal of delivering on the promise of stem cell therapies for human disease. Morris will work with stem cells from the Allen Cell Collection, mapping the steps cells take as they transition from stem cells to a range of clinically valuable cell types. Her team will make any technologies they develop through this project available to the research community. 

Affiliated Investigators

Samantha Morris, Ph.D.

Washington University in St. Louis

Samantha Morris is an Assistant Professor of Genetics and Developmental Biology at Washington University in St. Louis. Her laboratory studies the mechanisms of cell reprogramming, focusing on how pioneer transcription factors drive gene expression, epigenetic, and functional changes in cell identity. To enable these studies, her group develops novel, open-source single-cell experimental and computational approaches to longitudinally record lineage and gene regulation during directed reprogramming. Her laboratory recently developed and validated an innovative cell tracking technology called CellTagging. The application of this lineage tracing method revealed that cells reprogram along two distinct trajectories: one leading to desired cell identity and one leading to a dead-end state. As an example of how this technology can improve cellular reprogramming, CellTagging identified genes that, when exogenously expressed, increased the percentage of cells that would ultimately achieve the desired cell fate. With her team, Dr. Morris aims to engineer clinically relevant cell populations, translating new insights in cell fate specification into better models of disease and development. With clinical collaborators, her laboratory uses their genomic technologies to dissect mechanisms of pediatric gastrointestinal disease, such as Short Gut Syndrome and Hirschsprung’s Disease, with a long-term goal of developing novel regenerative therapies.

Dr. Morris trained as a developmental biologist at the University of Cambridge. In Magdalena Zernicka-Goetz's group, she investigated mechanisms of cell fate decision-making in the earliest stages of development. She then joined the laboratory of George Daley at Harvard Medical School, where she focused on the analysis of gene regulatory networks to dissect and engineer cell identity. In 2015, she established her independent research group. In 2017, Dr. Morris was named a Vallee Foundation Scholar, and in 2019, she was awarded the St. Louis Academy of Science Innovation Award. She sits on the Board of Directors of the Society for Developmental Biology and serves on the editorial boards of Development, Cell Systems, and Developmental Cell.