Research Roundup: February 1, 2019

Welcome to the February 1, 2019 installment of Research Roundup, a recurring snapshot of recent studies published by scientists at the Broad Institute and their collaborators.

Digging into developmental biology with 18th century math

Single-cell RNA-sequencing (scRNA-seq) delivers enormous amounts of data about cell state. But scRNA-seq destroys a cell, making it to hard trace a cell's developmental progression. In Cell, postdoctoral fellows Geoff Schiebinger, Jian Shu, and Marcin Tabaka, along with graduate student Brian Cleary, research scientist Vidya Subramanian, core institute member and Klarman Cell Observatory director Aviv Regev, founding director Eric Lander, and colleagues describe how they employed a mathematical technique called optimal transport — first developed in the 1780s to help engineers move piles of dirt efficiently — to string scRNA-seq snapshots of reprogramming fibroblasts into movies that unearth new details about how the induced pluripotent stem cell process works. Learn more in a Broad news story and video.

A novel CLL model

The splicing factor SF3B1 is frequently mutated in chronic lymphocytic leukemia (CLL), but it’s unclear how those mutations might cause disease. In Cancer Cell, institute member Catherine Wu of the Broad Cancer Program, Lili Wang (Dana Farber Cancer Institute), Shanye Yin (Harvard Medical School), and colleagues describe a new mouse model of CLL, in which B cells conditionally express mutated Sf3b1, leading to cellular senescence. They were able to overcome that senescence and induce CLL by also deleting the DNA damage-response gene Atm. They found that both human and mouse cells harboring mutant SF3B1 have B cell receptor signaling problems, and display altered sensitivity to ibrutinib, which blocks B cell receptor signaling.

Morning lark or night owl — genes can tell

Chronotype, a person’s preference for earlier or later sleep timing, is influenced by a variety of factors, including age, gender, environmental light levels, social constraints, and genetic variation. In a study published in Nature Communications, a team led by postdoctoral scholar Jacqueline Lane, associate member Richa Saxena of the Program in Medical and Population Genetics, and collaborators analyzed genome-wide data from 697,828 individuals, finding 327 new loci that also influence objective sleep timing. Overall the study provides additional insights into humans' daily biological (circadian) cycles and identifies links with mental health. Learn more in a MGH press release.

Sorting immune cells with microfluidics

In Science Advances, a team led by graduate student Miguel Reyes, institute member and Cell Ciruits Program co-director Nir Hacohen, and core institute member Paul Blainey describes a prototype microfluidics device that sorts cell types extracted from clinical samples for RNA sequencing. Such a platform could streamline this laboratory workflow and potentially fill the gap between bulk and single-cell RNA sequencing of blood samples — helping researchers efficiently scale up their efforts in large studies. As a pilot analysis, the team analyzed immune cells from patients with systemic lupus erythematosus and healthy individuals, and found that a classic lupus gene expression signature is expressed primarily in B cells. Read more in a Broad news story.

To learn more about research conducted at the Broad, visit broadinstitute.org/publications, and keep an eye on broadinstitute.org/news.