University of Michigan

Leland Stanford Junior University

Oncomed Pharmaceuticals, Inc.

Cz Biohub Sf, Llc.

Chan Zuckerberg Biohub, Inc.

Michael F Clarke

Bernhard O Palsson

Max S Wicha

Stephen G Emerson

Muhammad Al-Hajj

Sean J Morrison

Scott J Dylla

Piero D Dalerba

Alice S Chuck

Austin L Gurney

Stephen R Quake

Sanjeev Satyal

Richard Schwartz

Maximilian Diehn

R Douglas Armstrong

Diane M Simeone

Jianbin Wang

Huiping Liu

Tomer Kalisky

Anne A Leyrat

Xinhao Wang

Neethan A Lobo

Irving L Weissman

John A Lewicki

Aaron M Newman

Laurie Elizabeth Ailles

Tim Hoey

Maider Zabala Ugalde

Jane Antony

Shaheen Shabbir Sikandar

Michael Rothenberg

Maddalena Adorno

Gunsagar S Gulati

Mark Prince

Grace Chen

Robert W Hsieh

Anne Leyrat

Maximillian Diehn

Sean J Univ Of Michigan Med School Morrison

Muhammad Dept Of Internal Medicine Al-Hajj

Processes to infer stemness, cell lineage, and/or differentiation status are provided. In some instances, single cell RNA sequencing is used to infer a cell's stemness, cell lineage, and/or differentiation status. In some instances, a collection of cells is ordered based on each cell's differentiation status.

Methods utilizing single cell genetic data for cell population analysis and applications thereof

This disclosure provides data showing that LEFTY inhibits differentiation-promoting pathways such as BMP7/pSMAD5 in breast cancer cell lines, over and above its known role of inhibiting Nodal/pSMAD2. LEFTY competes with BMP7 to bind to its cell surface receptor BMPR2, leading to inhibition of pSMAD5. The LEFTY-BMPR2 interaction is dominant over BMP-BMPR2 in tumorigenic cells, resulting in diminished pSMAD status, whereas in non-tumorigenic cells, there is minimal LEFTY-BMPR2 interaction, increased BMP7-BMPR2 association, and elevated pSMAD. Compositions and methods for inducing or inhibiting expression and/or the activity of LEFTY and BMP proteins are described, which can be used in diagnosis and therapy of cancer and other conditions, and to promote proliferation of stem cells.

Compositions and methods for modulating left-right differentiation factor (LEFTY) and bone morphogenic factor (BMP)

The invention is directed to methods of treating TNBC in a patient by administering to the patient an agent that inhibits the expression or activity of cyclin-dependent kinase 19 (CDK19). In some embodiments, the agent may be a small molecule inhibitor, a polynucleotide (e.g., shRNA. siRNA), or a protein (e.g., an antibody). In some embodiments, the agent does not inhibit the activity or expression of CDK8.

Methods for treating triple-negative breast cancer

A small percentage of cells within an established solid tumor have the properties of stem cells. These solid tumor stem cells give rise both to more tumor stem cells and to the majority of cells in the tumor that have lost the capacity for extensive proliferation and the ability to give rise to new tumors. Thus, solid tumor heterogeneity reflects the presence of tumor cell progeny arising from a solid tumor stem cell. This discovery is the basis for solid tumor stem cell compositions, methods for distinguishing functionally different populations of tumor cells, methods for using these tumor cell populations for studying the effects of therapeutic agents on tumor growth, and methods for identifying and testing novel anti-cancer therapies directed to solid tumor stem cells.

Isolation and use of solid tumor stem cells

Methods are provided for diagnosis and prognosis of disease by analyzing expression of a set of genes obtained from single cell analysis. Classification allows optimization of treatment, and determination of whether on whether to proceed with a specific therapy, and how to optimize dose, choice of treatment, and the like. Single cell analysis also provides for the identification and development of therapies which target mutations and/or pathways in disease-state cells.

Methods and systems for analysis of single cells

Methods and compositions are provided for the treatment of medical conditions associated with a reduced rate of stem cell self-renewal or that will be responsive to an increased rate of stem cell self-renewal. Aspects of the methods include inhibiting H2A deubiquitinating enzyme activity in cells, e.g. by administering an effective amount of an H2A deubiquitinating enzyme antagonist. Also provided are screens to identify therapeutics for the treatment of medical conditions associated with a reduced rate of stem cell self-renewal or that will be responsive to an increased rate of stem cell self-renewal.

Targeting chromatin modifiers for the treatment of medical conditions

A small percentage of cells within an established tumor have the properties of stem cells. These solid tumor stem cells give rise both to more tumor stem cells and to the majority of cells in the tumor that have lost the capacity for extensive proliferation and the ability to give rise to new tumors. The solid tumor heterogeneity reflects the presence of tumor cell progeny arising from a solid tumor stem cell. This discovery is the basis for solid tumor stem cell compositions, methods for distinguishing functionally different populations of tumor cells, methods for using these tumor cell populations for studying the effects of therapeutic agents on tumor growth, and methods for identifying and testing novel anti-cancer therapies directed to solid tumor stem cells.

Single cell gene expression for diagnosis, prognosis and identification of drug targets

The invention provides methods for treating cancer via administering to a patient having a solid tumor a therapeutically effective amount of an antibody against Delta-like ligand 4(Dll4) or other Notch pathway components. The solid tumor may comprise solid tumor stem cells.

Method for treating cancer using an antibody that inhibits notch4 signaling

Squamous carcinoma stem cells (SCSC) are identified. The cells can be prospectively isolated or identified from primary tumor samples, and are shown to possess the unique properties of cancer stem cells in functional assays for cancer stem cell self-renewal and differentiation, and to form unique histological microdomains useful in cancer diagnosis.

Identification and isolation of squamous carcinoma stem cells

The present invention relates to the field of oncology and provides novel compositions and methods for diagnosing and treating pancreatic cancer. In particular, the present invention provides pancreatic cancer stem cells useful for the study, diagnosis, and treatment of solid tumors.

Compositions and methods for treating and diagnosing pancreatic cancer

A small percentage of cells within an established solid tumor have the properties of stem cells. These solid tumor stem cells give rise both to more tumor stem cells and to the majority of cells in the tumor that have lost the capacity for extensive proliferation and the ability to give rise to new tumors. Thus, solid tumor heterogeneity reflects the presence of tumor cell progeny arising from a solid tumor stem cell. We have developed a xenograft model in which we have been able to establish tumors from primary tumors via injection of tumor cells in the mammary gland of severely immunodeficient mice. These xenograft assay have allowed us to do biological and molecular assays to characterize clonogenic solid tumor stem cells. We have also developed evidence that strongly implicates the Notch pathway, especially Notch 4, as playing a central pathway in carcinogenesis.

Determining the capability of a test compound to affect solid tumor stem cells

A small percentage of cells within an established solid tumor have the properties of stem cells. These solid tumor stem cells give rise to both more tumor stem cells and to the majority of cells in the tumor that have lost the capacity for extensive proliferation and the ability to give rise to new tumors. Thus, solid tumor heterogeneity reflects the presence of tumor cell progeny arising from a solid tumor stem cell. We have developed a xenograft model in which we have been able to establish tumors from primary tumors via injection of tumors in the mammary gland of severely immunodeficient mice. These xenograft assay have allowed us to do biological and molecular assays to characterize clonogenic solid tumor stem cells. We have also developed evidence that strongly implicates the Notch pathway, especially Notch 4, as playing a central pathway in carcinogenesis.

Growing community of inventors

Palo Alto, CA, United States of America

Michael F Clarke