Genetics + Genomics

Cultured human cells are the foundation for disease and drug research. Now Whitehead Institute researchers have designed a growth medium that more closely resembles the cells’ environment in the body—and demonstrated that, relative to decades-old recipes that have remained the workhorses of cell culture studies, it significantly alters the cells’ inner workings.

Investigators at Whitehead Institute and the Broad Institute have succeeded in identifying the set of essential genes—those required for cellular proliferation and survival—in each of 14 human acute myeloid leukemia (AML) cell lines that had previously been characterized by genome sequencing. By combining their “gene essentiality map” with the existing genomic information, their study revealed liabilities in genetically defined subset of cancers that could be exploited for new therapies.

Whitehead researchers provide insight into a specific gene pathway that appears to regulate the growth, structure, and organization of the human cortex. They also demonstrate that 3D human cerebral organoids--miniature, lab-grown versions of specific brain structures--can be effective in modeling the molecular, cellular, and anatomical processes of human brain development. And they suggest a new path for identifying the cells affected by Zika virus.

Whitehead Institute scientists have deciphered how to use a modified CRISPR/Cas9 gene editing system to change genes’ methylation state, thereby activating or silencing those genes. Proper methylation is critical for normal cellular operations and altered methylation has been linked to many diseases, including neurological disorders and cancer.

Inherited methylation—a form of epigenetic regulation passed down from parents to offspring—is far more dynamic than previously thought and may contribute to changes in the brain and other tissues over time. This finding by Whitehead Institute scientists challenges current understandings of gene regulation via methylation, from development through adulthood.  

Whitehead Institute scientists have created a checklist that defines the “naive” state of cultured human embryonic stem cells (ESCs).  Such cells provide a better model of early human embryogenesis than conventional ESCs in later stages of development.