Abstract: 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.

Abstract: 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.

Abstract: 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.

Abstract: 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.

Abstract: The subject matter disclosed herein is generally directed to stratifying and treating coronavirus infections based on intrinsic immune states.

Abstract: This disclosure describes improvements 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, improved portability and case of use, increased scalability of the assay, and linkage of transcript information to other measurements made in the picowell arrays.

Abstract: 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.

Abstract: 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.

Abstract: The subject matter disclosed herein is generally directed to stratifying and treating inflammatory diseases. In particular, the present invention provides for detecting treatment naive cell states that predict the response of a subject having inflammatory bowel disease to anti-TNF-blockade. The cells are T cells, NK cells, innate lymphoid cells, myeloid and/or epithelial cell subsets defined by their gene expression as determined by single cell RNA sequencing. Alternatively, the responders are identified by gene expression in a sample.

Abstract: The subject matter disclosed herein is generally directed to stratifying and treating coronavirus infections based on intrinsic immune states.

Abstract: 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.

Abstract: 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 IFN?, IL-2, TNF, and/or IL-17 in systemic and/or lung T cells. In some embodiments, the increase of expression of IFN?, 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 Mycobacterium tuberculosis (MTB) infection.

Abstract: 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.

Abstract: The subject matter disclosed herein is generally directed to modulation of genes and pathways that drive differentiation of LGR5+ stem cells. The methods and compositions can be used to treat diseases associated with aberrant epithelial barrier function. Using novel screening methods Applicants have identified compounds that increase Paneth cell differentiation. The compounds can be used to treat diseases associated with stem cell differentiation.

Abstract: 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.

Abstract: 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.

Abstract: 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.

Abstract: 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.

Abstract: 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.

Abstract: 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.