Publications and Posters


Common human genetic variants of APOE impact murine COVID-19 mortality

Benjamin N. Ostendorf, Mira A. Patel, Jana Bilanovic, H.-Heinrich Hoffmann, Sebastian E. Carrasco, Charles M. Rice, and Sohail. F. Tavazoie
WT Mouse Lung
Lung tissue from knock-in mice expressing common variants of human APOE (APOE2, APOE3 and APO4) showed differences in gene expression that causally impacted the outcome of COVID-19 infection. APOE2 and APOE4 knock-in mice had increased disease progression and mortality relative to APOE3 knock-in mice. Human data from the UK Biobank supports the finding that genetic variation in APOE partially explains the variation in severity of COVID-19 disease outcomes.


Single-cell transcriptome landscape of circulating CD4+ T cell populations in human autoimmune diseases

Yoshiaki Yasumizu, Daiki Takeuchi, Reo Morimoto, Yusuke Takeshima, Tatsusada Okuno, Makoto Kinoshita, Takayoshi Morita, Yasuhiro Kato, Min Wang, Daisuke Motooka, Daisuke Okuzaki, Yamami Nakamura, Norihisa Mikami, Masaya Arai, Xuan Zhang, Atsushi Kumanogoh, Hideki Mochizuki, Naganari Ohkura, Shimon Sakaguchi
WT Mega Human PBMCs
CD4+ T cell scRNA-seq data from healthy individuals and various autoimmune disease patients, were clustered by applying a decomposition based, non-negative matrix factorization (NMF) into 12 independent transcriptional gene programs. Metanalyses of freely available scRNA-seq datasets revealed that the 12 transcriptional programs could characterize each autoimmune disease and predict its clinical status with a resolution difficult to obtain with existing methodologies.

Development of Matrix-Embedded Bovine Tracheal Organoids to Study the Innate Immune Response against Bovine Respiratory Disease

Pin Shie Quah, Bang M. Tran, Vincent D.A. Corbin, Jessie J.-Y. Chang, Chinn Yi Wong, Andrés Diaz-Méndez, Carol A. Hartley, Weiguang Zeng, Eric Hanssen, Zlatan Trifunovic, Patrick C. Reading, David C. Jackson, Elizabeth Vincan, Lachlan J.M. Coin, Georgia Deliyannis
WT Mini Bovine Tracheal Organoids
To enhance research into BHV-1, a bovine tracheal organoid culture was developed using a 3-D matrix system. scRNA-seq showed consistent cell differentiation and transcriptomic profiles compared to conventional 2-D systems. The organoids were vulnerable to BHV-1 infection and produced a robust immune response to stimulation by Pam2Cys, demonstrating the utility of the model system in studying viral infection.

Mesenchymal stem cells ameliorate inflammation in an experimental model of Crohn's disease via the mesentery

Maneesh Dave, Atul Dev, Rodrigo A Somoza, Nan Zhao, Satish Viswanath, Pooja Rani Mina, Prathyush Chirra, Verena Carola Obmann, Ganapati H Mahabeleshwar, Paola Menghini, Blythe Durbin Johnson, Jan A Nolta, Christopher Soto, Abdullah Osme, Lam T Khuat, William Murphy, Arnold I Caplan, Fabio Cominelli
WT Human MSCs
Human Mesenchymal Stem Cells (hMSC) modulate T cells and macrophages when administered into a Chron’s disease model. scRNA-seq showed long-term anti-inflammatory macrophage reprogramming, providing evidence of prolonged therapeutic effects of hMSC.

Characterization of Pro-Fibrotic Signaling Pathways using Human Hepatic Organoids

Yuan Guan, Zhuoqing Fang, Angelina Hu, Sarah Roberts, Patrik K. Johansson, Sarah C. Heilshorn, Annika Enejder, Gary Peltz
WT Mini Human Liver
In a human hepatic organoid model, scRNA-seq was used to identify the ligand responsible for the development of liver fibrosis among competing hypotheses. Transcriptomic analysis revealed that TGFβ1 exposure converted mesenchymal cells into myofibroblast-like cells, with significantly increased expression of proteases, anti-protease, and extracellular matrix genes, which contribute to the development of liver fibrosis.

High-quality functional association networks inferred from scRNA-seq and proteomics data

Mikaela Koutrouli, Pau Piera Líndez, Robbin Bouwmeester, Simon Rasmussen, Lennart Martens, Lars Juhl Jensen
Introduces FAVA, a novel analysis method to handle large-scale scRNA-seq and proteomic data, predict high-confidence functional associations, and provide good coverage for understudied proteins. Performance was evaluated using freely available proteomic and PBMC scRNA-Seq datasets.

Human iPS cell-derived sensory neurons can be infected by SARS-CoV-2 strain WA1/2020 as well as variants delta and omicron

Anthony Flamier, Punam Bisht, Alexsia Richards, Danielle Tomasello, Rudolf Jaenisch
WT Mini Human iPS
In COVID-19-infected human sensory neurons, scRNA-seq was critical in revealing that sensory neurons can be infected by SARS-CoV-2 but are unable to produce new viruses. This may have implications for understanding the infection’s long-term impact on the peripheral nervous system.

Notch Inhibition Promotes Regeneration and Immunosuppression Supports Cone Survival in a Zebrafish Model of Inherited Retinal Dystrophy

Joseph Fogerty, Ping Song, Patrick Boyd, Sarah E. Grabinski, Thanh Hoang, Adrian Reich, Lauren T. Cianciolo, Seth Blackshaw, Jeff S. Mumm, David R. Hyde, and Brian D. Perkins
WT Zebrafish Retina
In a zebrafish model of progressive retinal degeneration, inflammation alone was not sufficient to trigger Müller glia reprogramming into multipotent retinal progenitors. Single cell RNA-seq showed that notch signaling remained active with progressive degeneration in contrast to what has been seen previously with acute injury.

High sensitivity single cell RNA sequencing with split pool barcoding

Vuong Tran, Efthymia Papalexi, Sarah Schroeder, Grace Kim, Ajay Sapre, Joey Pangallo, Alex Sova, Peter Matulich, Lauren Kenyon, Zeynep Sayar, Ryan Koehler, Daniel Diaz, Archita Gadkari, Kamy Howitz, Maria Nigos, Charles M. Roco, and Alexander B. Rosenberg
WT Mouse Brain Mouse Liver Human PBMCs Cell Lines
A detailed performance evaluation of Evercode™ WT v2 that highlights improved gene and transcript detection, robustness across samples, and no bias in gene expression data. Multiple sample types were assessed, including cells and nuclei.

High dimensional co-expression networks enable discovery of transcriptomic drivers in complex biological systems

Samuel Morabito, Fairlie Reese, Negin Rahimzadeh, Emily Miyoshi, and Vivek Swarup
WT Mega Human PBMCs
Introduces hdWGCNA, an analysis framework supporting system-level analysis of data from complex biological systems. Data was integrated from the 1M Evercode WT Mega v1 Type-1 Diabetes dataset from human PBMCs to demonstrate utility and scalability.

Single-nuclei transcriptomics of mammalian prion diseases identifies dynamic gene signatures shared between species

Athanasios Dimitriadis, Fuquan Zhang, Thomas Murphy, Thomas Trainer, Zane Jaunmuktane, Christian Schmidt, Tamsin Nazari, Jacqueline Linehan, Sebastian Brandner, John Collinge, Simon Mead, and Emmanuelle Viré
WT Mouse Brain
Gene expression studies on the brains of mice with prion disease identified shared gene signatures with human prion disease, providing clues to molecular mechanisms. Incorporation of a protein denaturation step allowed the removal of the samples from a BSL-3 to a BSL-2 lab for the library preparation and sequencing steps.

Directed Differentiation of Human iPSCs to Functional Ovarian Granulosa-Like Cells via Transcription Factor Overexpression

Merrick Pierson Smela, Christian Kramme, Patrick Fortuna, Jessica Adams, Edward Dong, Mutsumi Kobayashi, Garyk Brixi, Emma Tysinger, Richie. E. Kohman, Toshi Shioda, Pranam Chatterjee, and George M. Church
WT Mega Human iPSCs
Two transcription factors required for the development of ovarian granulosa cells, (a necessary and previously lacking component of human ovary organoids) were identified. Human iPSCs were induced to differentiate into human ovary organoids, whose identities were confirmed based on differential gene expression.

Absence of microglia promotes diverse pathologies and early lethality in Alzheimer’s disease mice

Sepideh Kiani Shabestari, Samuel Morabito, Emma Pascal Danhash, Amanda McQuade, Jessica Ramirez Sanchez, Emily Miyoshi, Jean Paul Chadarevian, Christel Claes, Morgan Alexandra Coburn, Jonathan Hasselmann, Jorge Hidalgo, Kayla Nhi Tran, Alessandra C. Martini, Winston Chang Rothermich, Jesse Pascual, Elizabeth Head, David A. Hume, Clare Pridans, Hayk Davtyan, Vivek Swarup, and Mathew Blurton-Jones
WT Mouse Brain
Microglia are brain cells with a role in Alzheimer’s Disease development and progression. A knock-out mouse model revealed a role for microglia in protecting brains by removing calcium deposits.

Mapping and modeling the genomic basis of differential RNA isoform expression at single-cell resolution with LR-Split-seq

Elisabeth Rebboah, Fairlie Reese, Katherine Williams, Gabriela Balderrama-Gutierrez, Cassandra McGill, Diane Trout, Isaryhia Rodriguez, Heidi Liang, Barbara J. Wold, and Ali Mortazavi
WT Cell Lines
Full length transcript isoforms were identified using long-read sequencing on the PacBio platform with a protocol modification described as LR-Split-Seq. Applying this approach in mouse muscle cell lines, previously known and novel alternatively spliced transcript isoforms were detected.