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Research Roundup: November 5, 2021

Susanna M. Hamilton
Credit : Susanna M. Hamilton
By Broad Communications

Bone-building networks, spatial sperm transcriptomics, molecular biology of well-stimulated brain, and more

Welcome to the November 5, 2021 installment of Research Roundup, a recurring snapshot of recent studies published by scientists at the Broad Institute and their collaborators.

Boning up on osteocyte formation

A new study helps explain how osteoblasts make connections as they become osteocytes, important cells for maintaining bone strength. Jialiang Wang (MGH/HMS), Tushar Kamath, Pearl Ryder, associate member Marc Wein of the Metabolism Program and of Harvard Stem Cell Institute, and others demonstrated that the transcription factor Sp7 orchestrates osteocyte dendrite formation by targeting the osteocrin gene, which promotes dendrite formation and can restore healthy bone cell connectivity. Single-cell profiling showed that osteocytes in bone and neurons in the brain share a common core set of dendrite-associated genes. The work suggests new ways to target osteocyte connectivity for treatment of osteoporosis. Read more in Nature Communications and a Mass General press release.

Spatial transcriptomics of mammalian spermatogenesis

The molecular basis of spermatogenesis, or sperm production, is not yet fully understood. While single-cell RNA sequencing illustrates diversity in gene expression profiles, it cannot capture germ cells in the context of the seminiferous tubule, the functional unit of spermatogenesis. Now, Haiqi Chen, core institute member Fei Chen, and colleagues use Slide-seq, a high throughput spatial transcriptomics technique, to generate transcriptomic atlases of mouse and human testes at near-single-cell resolution. The findings reveal significant differences in cellular organization between organisms and also indicate that a disruption in spatial cellular organization may underlie diabetes-induced infertility in mice. Read more in Cell Reports and a tweetorial by Haiqi.

MEF2 marks cognitive resilience 

A cognitively stimulating environment is known to improve resilience to neurodegeneration. To find markers of cognitive resilience (CgR), associate member Li-Huei Tsai (MIT) and colleagues profiled molecular changes in mice experiencing environmental enrichment and analyzed human clinical and brain transcriptomic data. They discovered that the MEF2 family of transcription factors was upregulated in cognitively-stimulated mice as well as in humans with CgR. Overexpression of MEF2 in a mouse model of neurodegeneration confirmed its functional role in driving environment-induced CgR. Read more in Science Translational Medicine about MEF2 as a biomarker for CgR and potential therapeutic target.

A ten-fold path for computational biology

Computational biology has grown and matured dramatically as a field over the last three decades. But while much of modern biological and biomedical science rely on computation and collaboration, career development for computational biologists is still largely ad hoc, and some still question the role of this kind of team-based science in biology. In PLOS Biology, Greg Way, institute scientist and Imaging Platform director Anne Carpenter, Elana Fertig (Johns Hopkins), and 13 fellow computational biologists describe ten steps through which the biological sciences can embrace a deep integration between biology and computer science, align pathways of scientific progress and career success for computational biologists, and embrace a multi-disciplinary, data-driven approach to science.

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

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