Massachusetts Institute of Technology

The Broad Institute, Inc.

Harvard College

The General Hospital Corporation

The Brigham and Women's Hospital, Inc.

Other

University of California

National Institutes of Health, a Component of the US Dept. of Health & Human Services

University of Pittsburgh

Dana-farber-cancer Institute Inc.

Alexander K Shalek

Aviv Regev

Hongkun Park

Travis K Hughes

J Christopher Love

Todd Michael Gierahn

Jellert Gaublomme

Marc H Wadsworth, Ii

Jose Ordovas-Montanes

Vijay K Kuchroo

Ramnik Xavier

Orit Rozenblatt-Rosen

Steven Andrew McCarroll

Anindita Basu

Rebecca H Herbst

Nir Yosef

Moshe Biton

Christopher B Ford

Evan Macosko

Jeffrey F Van Humbeck

Carly Ziegler

Christopher Smillie

Carly G K Ziegler

Alexander S Genshaft

Robert Samuel Langer

David A Weitz

Jeffrey Michael Karp

Eric Lander

Le Cong

Scott R Manalis

Chao Wang

Ana Carrizosa Anderson

Bradley Bernstein

Robert Seder

Jonathan S Weissman

Jinseok Lee

Thomas W Norman

Karthik Shekhar

Myung-Han Yoon

Atray Dixit

Brian Cleary

Volker Hovestadt

Adam Haber

Marsela Jorgolli

Peter Van Galen

Oren Parnas

Youjin Lee

Rahul Satija

Joanne L Flynn

Noga Rogel

Ryan Philip King

Shaina Carroll

Benjamin E Mead

Brittany Adamson

Patricia Darrah

Alethe Gaillard De Saint Germain

Andrew Navia

Jennyfer Galvez-Reyes

Ang A Tu

Amy Sutton

Jacob Robinson

EunGyeong Yang

Marc Havens Wadsworth

Chuan Wu

Nicole C Joller

David Weinstock

Peter Winter

Mark Murakami

Zhengyu Ouyang

Enrique Martin Gayo

Kellie E Kolb

Xu Yu

Michael B Cole

Evan Zane Macosko

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 tools and methods for the systematic analysis of genetic interactions between cells. The present invention provides tools and methods for modulating cell phenotypes and compositions, combinatorial probing of cellular circuits, for dissecting cellular circuitry, for delineating molecular pathways, and/or for identifying relevant targets for therapeutics development.

Methods for identifying and modulating co-occurant cellular phenotypes

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

The present application provides a method of assembling a container for one or multiple parallel steps of biochemical analysis on one or more cells comprising performing molecular bonding of a porous membrane on an apical or basal surface of an array having a plurality of wells, wherein the molecular bonding substantially isolates each well from adjacent wells.

Semi-permeable arrays for analyzing biological systems and methods of using same

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

Provided herein are compositions and methods for therapeutic and/or prophylactic treatment of an intracellular bacterial infection in a subject in need thereof, comprising one or more modulating agents, wherein the one or more modulating agents increase expression of IFNγ, IL-2, TNF, and/or IL-17 in systemic and/or lung T cells. In some embodiments, the increase of expression of IFNγ, IL-2, TNF, and/or IL-17 occurs in lung T cells. The lung T cells can be lung resident T cells or systemic T cells that are recruited to the lung. In some embodiments, the T cells are CD4+ and/or CD8+ T cells. In some embodiments, the intracellular bacterial infection is a(MTB) infection.

Compositions and methods for treating bacterial infections

Described in exemplary embodiments herein are methods, compositions, and kits for diagnosing, prognosing, monitoring, treating and/or preventing a hemopoietic malignancy and/or relapse thereof in a subject. In some embodiments, the methods can include determining an average cellular mass of cells in a sample from the subject and/or detecting one or more molecular signatures in one or more of the cells. In some embodiments, treatment includes administering one or more BCR-ABL tyrosine kinase inhibitors or a pharmaceutical formulation thereof, one or more pre-BCR signaling pathway inhibitors or a pharmaceutical formulation thereof, one or more p38 MAPK inhibitors or a pharmaceutical formulation thereof; or any combination thereof.

Methods and compositions for predicting and preventing relapse of acute lymphoblastic leukemia

Embodiments disclosed herein provide a pan-tissue cell atlas of healthy and diseased subjects obtained by single cell sequencing. The present invention discloses novel markers for cell types. Moreover, genes associated with disease, including HIV infection and tuberculosis are identified. The invention provides for diagnostic assays based on gene markers and cell composition, as well as therapeutic targets for controlling immune regulations and cell-cell communication of the cell types disclosed herein. In addition, novel cell types and methods of quantitating, detecting and isolating the cell types are disclosed.

Markers of active HIV reservoir

Modifications to both hardware and enzymatic reactions used in single cell analyses such as but not limited to Seq-well that enable significant increases in the yield of transcripts per cell, portability and ease of use, increased scalability of the assay, and linkage of transcript information to other measurements made in the picowell arrays are disclosed.

Single cell analyses

The present invention relates to methods of detecting region(s) of interest in a gene comprising a polyA tail. The region(s) of interest can include gene(s), region(s), mutation(s), deletion(s), insertion(s), indel(s), and/or translocation(s). The region(s) can be greater than or less than 1 kilobases from the polyA tail. Methods can include forming a library of single cell transcripts comprising the region(s) in close proximity to a cell barcode and a unique molecular identifier (UMI). Methods for distinguishing cells by genotype can include amplifying the transcripts using PCR methods and detecting the cell barcode and UMI using single cell sequencing methods. Transcripts can be enriched using tagged region-specific PCR primers. Cell barcodes can be brought into close proximity to the region(s) by circularizing the transcripts. Sequencing of the transcripts can include using primer binding sites added during PCR amplification and library indexes for multiplexed sequencing.

Single cell sequencing libraries of genomic transcript regions of interest in proximity to barcodes, and genotyping of said libraries

Gene expression signatures and pathways associated with tuberculosis are identified. The invention provides for diagnostic assays based on gene markers and cell composition, as well as therapeutic targets for modulating tuberculosis infection. In addition, tuberculosis copy number contained in cells and methods of detecting high and low copy number are disclosed.

host-pathogen interaction

The present invention relates to systems and methods for recording and assaying cellular events, in particular gene expression. The invention provides hereto a method of determining a cellular event of interest in a cell comprising providing a cell comprising a CRISPR-Cas system, wherein the CRISPR-Cas system comprises a guide RNA that targets a selected DNA sequence and a Cas protein capable of modifying the selected DNA sequence; whereby a nucleic acid molecule encoding at least one of the guide RNA or Cas protein is operably connected in the cell with a regulatory element comprising a promoter responsive to the cellular event, and whereby expression of at least one CRISPR-Cas system component is driven by the promoter; and determining cellular event of interest based on detection of the modification of the selected DNA sequence.

CRISPR mediated recording of cellular events

The present invention generally relates to a combination of molecular barcoding and emulsion-based microfluidics to isolate, lyse, barcode, and prepare nucleic acids from individual cells in a high-throughput manner.

Droplet-based method and apparatus for composite single-cell nucleic acid analysis

Growing community of inventors

Cambridge, MA, United States of America

Alexander K Shalek