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Welcome to the October 16, 2020 installment of Research Roundup, a recurring snapshot of recent studies published by scientists at the Ó³»­´«Ã½ and their collaborators.

CHIPping away at MPN risk 

Certain mutations in hematopoietic stem cells that accumulate with age can eventually cause cancer or predispose people to cardiovascular disease. Two teams, including Alexander Bick, Erik Bao, Satish Nandakumar, Xiaotian Liao, associate members Pradeep Natarajan (Massachusetts General Hospital) and Vijay Sankaran (Boston Children’s Hospital and Dana-Farber Cancer Institute) in the Program in Medical and Population Genetics (MPG), and colleagues have found inherited gene variants that increase the risk of acquiring these mutations in HSCs over people’s lifetimes. These mutations lead to one of two age-related blood disorders: myeloproliferative neoplasms (MPNs) and clonal hematopoiesis of indeterminate potential (CHIP). The findings show that some of the inherited gene variants boost blood stem cell self-renewal, potentially resulting in an expanded pool of blood stem cells that can lead to MPNs or CHIP. Read more in papers and a Ó³»­´«Ã½ story.

An updated view of nuclear metabolism

Cellular metabolism supports all the cell’s biological activities, but the mechanisms regulating  metabolites in the nucleus are not well understood. In a (paywall) review article, postdoctoral scholars Ruben Boon and Giorgia Silveira and associate member Raul Mostoslavsky of Mass General and the Epigenomics Program highlight recent efforts to describe the mechanisms that influence metabolism in the nucleus and how metabolites are redistributed between the cell’s nuclear and non-nuclear compartments. The authors suggest that applying metabolism and epigenetics research to the nuclear metabolon can lead to novel ways of understanding cellular fate and potentially treating disease.

Once upon a time in Vanuatu

Humans have been passing through the Pacific archipelago of Vanuatu for more than 3,000 years. To gain a clearer picture of the history of these migrations, MPG associate member David Reich and colleagues studied the genomes of 45 ancient individuals from Vanuatu and elsewhere in Oceania, comparing their findings with data from modern-day populations. Their analysis reveals three distinct waves of settlement in the archipelago: first by people closely related to East and Southeast Asians; then by people likely from New Britain, east of Papua New Guinea; and lastly by multiple groups of Polynesian ancestry. Learn more in .

A new single-cell RNA-seq technique

In , a team led by Travis Hughes, Marc Wadsworth, Todd Gierahn (MIT), associate member J. Christopher Love, and institute member Alex Shalek describes a new single-cell RNA-sequencing protocol to boost the efficiency of high-throughput data collection. The new technique, called Seq-Well S3, increases the number of cells that can be profiled contemporaneously while capturing high-quality biological information. The researchers used the new protocol to analyze approximately 40,000 cells from patients with five different skin diseases, providing a resource for future study of human skin inflammation. Read more in an MIT and a  from Hughes.

A structural model of BAF for disease 

Approximately 20 percent of all human cancers and several neurodevelopmental and intellectual disability syndromes are linked to mutations in a group of chromatin-remodeling proteins called BAF. But little is known about BAF’s structure in humans and how it contributes to disease. Now, Nazar Mashtalir, Akshay Sankar, institute member and Epigenomics Program co-director Cigall Kadoch, and colleagues have generated the first structural model of the human BAF complex and found that disease-linked mutations cluster at key structural interfaces of the complex, weakening its chromatin-remodeling activity. Published in , these findings provide a powerful foundation for researchers to fully understand how BAF functions in both health and disease. Read more in a .

To learn more about research conducted at the Ó³»­´«Ã½, visit broadinstitute.org/publications, and keep an eye on broadinstitute.org/news.