Massachusetts Institute of Technology

The General Hospital Corporation

The Broad Institute, Inc.

The Brigham and Women's Hospital, Inc.

Jose Ordovas-Montanes

Alexander K Shalek

Aviv Regev

Ramnik Xavier

Moshe Biton

Rebecca H Herbst

Christopher Smillie

Robert Samuel Langer

Jeffrey Michael Karp

Orit Rozenblatt-Rosen

Karthik Shekhar

Adam Haber

Benjamin E Mead

Noga Rogel

An atlas of intestinal epithelial cells, intestinal epithelial stem cells and intestinal immune cells identifies new cell populations, markers, networks, and responses to stimuli. Intestinal T cells drive intestinal epithelial cell differentiation and activity. Accordingly, disclosed are methods of modulating intestinal epithelial cell differentiation, maintenance and/or function, related methods for the treatment of disease, including IBD. Also disclosed are methods and kits for identifying cell types, their differentiation, homeostasis and activation.

Modulation of intestinal epithelial cell differentiation, maintenance and/or function through T cell action

The present invention provides for a human cell atlas of the colon from healthy and diseased subjects. The atlas was obtained by single sequencing of about 117,000 cells. The present invention discloses novel markers for cell types. Moreover, genes associated with disease are identified in the colon and colon specific cell types. The invention provides for diagnostic assays based on gene markers and cell composition, as well as target cell types that express genes associated with disease. Finally, disclosed are novel cell types and methods of quantitating, detecting and isolating the cell types.

Cell atlas of the healthy and ulcerative colitis human colon

Disclosed here is a generally applicable framework that utilizes massively-parallel single-cell RNA-seq to compare cell types/states found in vivo to those of in vitro models. Furthermore, Applicants leverage identified discrepancies to improve model fidelity. Applicants uncover fundamental gene expression differences in lineage-defining genes between in vivo systems and in vitro systems. Using this information, molecular interventions are identified for rationally improving the physiological fidelity of the in vitro system. Applicants demonstrated functional (antimicrobial activity, niche support) improvements in Paneth cell physiology using the methods.

Single-cell genomic methods to generate ex vivo cell systems that recapitulate in vivo biology with improved fidelity

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Cambridge, MA, United States of America

Jose Ordovas-Montanes