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246 results on '"Ashenberg, Orr"'

1. Neuropeptide signalling orchestrates T cell differentiation

Author

Hou, Yu, Sun, Linyu, LaFleur, Martin W., Huang, Linglin, Lambden, Conner, Thakore, Pratiksha I., Geiger-Schuller, Kathryn, Kimura, Kimitoshi, Yan, Longjun, Zang, Yue, Tang, Ruihan, Shi, Jingwen, Barilla, Rocky, Deng, Liwen, Subramanian, Ayshwarya, Wallrapp, Antonia, Choi, Hee Sun, Kye, Yoon-Chul, Ashenberg, Orr, Schiebinger, Geoffrey, Doench, John G., Chiu, Isaac M., Regev, Aviv, Sharpe, Arlene H., and Kuchroo, Vijay K.

Published
2024
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2. A multi-modal single-cell and spatial expression map of metastatic breast cancer biopsies across clinicopathological features

Author

Klughammer, Johanna, Abravanel, Daniel L., Segerstolpe, Åsa, Blosser, Timothy R., Goltsev, Yury, Cui, Yi, Goodwin, Daniel R., Sinha, Anubhav, Ashenberg, Orr, Slyper, Michal, Vigneau, Sébastien, Jané‐Valbuena, Judit, Alon, Shahar, Caraccio, Chiara, Chen, Judy, Cohen, Ofir, Cullen, Nicole, DelloStritto, Laura K., Dionne, Danielle, Files, Janet, Frangieh, Allison, Helvie, Karla, Hughes, Melissa E., Inga, Stephanie, Kanodia, Abhay, Lako, Ana, MacKichan, Colin, Mages, Simon, Moriel, Noa, Murray, Evan, Napolitano, Sara, Nguyen, Kyleen, Nitzan, Mor, Ortiz, Rebecca, Patel, Miraj, Pfaff, Kathleen L., Porter, Caroline B. M., Rotem, Asaf, Strauss, Sarah, Strasser, Robert, Thorner, Aaron R., Turner, Madison, Wakiro, Isaac, Waldman, Julia, Wu, Jingyi, Gómez Tejeda Zañudo, Jorge, Zhang, Diane, Lin, Nancy U., Tolaney, Sara M., Winer, Eric P., Boyden, Edward S., Chen, Fei, Nolan, Garry P., Rodig, Scott J., Zhuang, Xiaowei, Rozenblatt-Rosen, Orit, Johnson, Bruce E., Regev, Aviv, and Wagle, Nikhil

Published
2024
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5. B-cell-specific checkpoint molecules that regulate anti-tumour immunity

Author

Bod, Lloyd, Kye, Yoon-Chul, Shi, Jingwen, Torlai Triglia, Elena, Schnell, Alexandra, Fessler, Johannes, Ostrowski, Stephen M., Von-Franque, Max Y., Kuchroo, Juhi R., Barilla, Rocky M., Zaghouani, Sarah, Christian, Elena, Delorey, Toni Marie, Mohib, Kanishka, Xiao, Sheng, Slingerland, Nadine, Giuliano, Christopher J., Ashenberg, Orr, Li, Zhaorong, Rothstein, David M., Fisher, David E., Rozenblatt-Rosen, Orit, Sharpe, Arlene H., Quintana, Francisco J., Apetoh, Lionel, Regev, Aviv, and Kuchroo, Vijay K.

Published
2023
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6. Single-cell meta-analysis of SARS-CoV-2 entry genes across tissues and demographics.

Author

Muus, Christoph, Luecken, Malte, Eraslan, Gökcen, Sikkema, Lisa, Waghray, Avinash, Heimberg, Graham, Kobayashi, Yoshihiko, Vaishnav, Eeshit, Subramanian, Ayshwarya, Smillie, Christopher, Jagadeesh, Karthik, Duong, Elizabeth, Fiskin, Evgenij, Torlai Triglia, Elena, Ansari, Meshal, Cai, Peiwen, Lin, Brian, Buchanan, Justin, Chen, Sijia, Shu, Jian, Haber, Adam, Chung, Hattie, Montoro, Daniel, Adams, Taylor, Aliee, Hananeh, Allon, Samuel, Andrusivova, Zaneta, Angelidis, Ilias, Ashenberg, Orr, Bassler, Kevin, Bécavin, Christophe, Benhar, Inbal, Bergenstråhle, Joseph, Bergenstråhle, Ludvig, Bolt, Liam, Braun, Emelie, Bui, Linh, Callori, Steven, Chaffin, Mark, Chichelnitskiy, Evgeny, Chiou, Joshua, Conlon, Thomas, Cuoco, Michael, Cuomo, Anna, Deprez, Marie, Duclos, Grant, Fine, Denise, Fischer, David, Ghazanfar, Shila, Gillich, Astrid, Giotti, Bruno, Gould, Joshua, Guo, Minzhe, Gutierrez, Austin, Habermann, Arun, Harvey, Tyler, He, Peng, Hou, Xiaomeng, Hu, Lijuan, Hu, Yan, Jaiswal, Alok, Ji, Lu, Jiang, Peiyong, Kapellos, Theodoros, Kuo, Christin, Larsson, Ludvig, Leney-Greene, Michael, Lim, Kyungtae, Litviňuková, Monika, Ludwig, Leif, Lukassen, Soeren, Luo, Wendy, Maatz, Henrike, Madissoon, Elo, Mamanova, Lira, Manakongtreecheep, Kasidet, Leroy, Sylvie, Mayr, Christoph, Mbano, Ian, McAdams, Alexi, Nabhan, Ahmad, Nyquist, Sarah, Penland, Lolita, Poirion, Olivier, Poli, Sergio, Qi, CanCan, Queen, Rachel, Reichart, Daniel, Rosas, Ivan, Schupp, Jonas, Shea, Conor, Shi, Xingyi, Sinha, Rahul, Sit, Rene, Slowikowski, Kamil, Slyper, Michal, Smith, Neal, Sountoulidis, Alex, Strunz, Maximilian, and Sullivan, Travis

Subjects
Adult, Aged, Aged, 80 and over, Alveolar Epithelial Cells, Angiotensin-Converting Enzyme 2, COVID-19, Cathepsin L, Datasets as Topic, Demography, Female, Gene Expression Profiling, Host-Pathogen Interactions, Humans, Lung, Male, Middle Aged, Organ Specificity, Respiratory System, SARS-CoV-2, Sequence Analysis, RNA, Serine Endopeptidases, Single-Cell Analysis, Virus Internalization
Abstract

Angiotensin-converting enzyme 2 (ACE2) and accessory proteases (TMPRSS2 and CTSL) are needed for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cellular entry, and their expression may shed light on viral tropism and impact across the body. We assessed the cell-type-specific expression of ACE2, TMPRSS2 and CTSL across 107 single-cell RNA-sequencing studies from different tissues. ACE2, TMPRSS2 and CTSL are coexpressed in specific subsets of respiratory epithelial cells in the nasal passages, airways and alveoli, and in cells from other organs associated with coronavirus disease 2019 (COVID-19) transmission or pathology. We performed a meta-analysis of 31 lung single-cell RNA-sequencing studies with 1,320,896 cells from 377 nasal, airway and lung parenchyma samples from 228 individuals. This revealed cell-type-specific associations of age, sex and smoking with expression levels of ACE2, TMPRSS2 and CTSL. Expression of entry factors increased with age and in males, including in airway secretory cells and alveolar type 2 cells. Expression programs shared by ACE2+TMPRSS2+ cells in nasal, lung and gut tissues included genes that may mediate viral entry, key immune functions and epithelial-macrophage cross-talk, such as genes involved in the interleukin-6, interleukin-1, tumor necrosis factor and complement pathways. Cell-type-specific expression patterns may contribute to the pathogenesis of COVID-19, and our work highlights putative molecular pathways for therapeutic intervention.

Published
2021

7. Inhibitory CD161 receptor identified in glioma-infiltrating T cells by single-cell analysis

Author

Mathewson, Nathan D, Ashenberg, Orr, Tirosh, Itay, Gritsch, Simon, Perez, Elizabeth M, Marx, Sascha, Jerby-Arnon, Livnat, Chanoch-Myers, Rony, Hara, Toshiro, Richman, Alyssa R, Ito, Yoshinaga, Pyrdol, Jason, Friedrich, Mirco, Schumann, Kathrin, Poitras, Michael J, Gokhale, Prafulla C, Gonzalez Castro, L Nicolas, Shore, Marni E, Hebert, Christine M, Shaw, Brian, Cahill, Heather L, Drummond, Matthew, Zhang, Wubing, Olawoyin, Olamide, Wakimoto, Hiroaki, Rozenblatt-Rosen, Orit, Brastianos, Priscilla K, Liu, X Shirley, Jones, Pamela S, Cahill, Daniel P, Frosch, Matthew P, Louis, David N, Freeman, Gordon J, Ligon, Keith L, Marson, Alexander, Chiocca, E Antonio, Reardon, David A, Regev, Aviv, Suvà, Mario L, and Wucherpfennig, Kai W

Subjects
Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Immunology, Rare Diseases, Immunization, Cancer, Genetics, Vaccine Related, Brain Disorders, Stem Cell Research, Neurosciences, Brain Cancer, Human Genome, Stem Cell Research - Nonembryonic - Human, Animals, Antigens, Neoplasm, Disease Models, Animal, Gene Expression Profiling, Glioma, Killer Cells, Natural, Lectins, C-Type, Lymphocytes, Tumor-Infiltrating, Mice, NK Cell Lectin-Like Receptor Subfamily B, Receptors, Cell Surface, Single-Cell Analysis, T-Lymphocyte Subsets, T-Lymphocytes, Tumor Escape, CD161, IDH-mutant gliomas, T cells, glioblastoma, single-cell RNA-seq, Biological Sciences, Medical and Health Sciences, Developmental Biology, Biological sciences, Biomedical and clinical sciences
Abstract

T cells are critical effectors of cancer immunotherapies, but little is known about their gene expression programs in diffuse gliomas. Here, we leverage single-cell RNA sequencing (RNA-seq) to chart the gene expression and clonal landscape of tumor-infiltrating T cells across 31 patients with isocitrate dehydrogenase (IDH) wild-type glioblastoma and IDH mutant glioma. We identify potential effectors of anti-tumor immunity in subsets of T cells that co-express cytotoxic programs and several natural killer (NK) cell genes. Analysis of clonally expanded tumor-infiltrating T cells further identifies the NK gene KLRB1 (encoding CD161) as a candidate inhibitory receptor. Accordingly, genetic inactivation of KLRB1 or antibody-mediated CD161 blockade enhances T cell-mediated killing of glioma cells in vitro and their anti-tumor function in vivo. KLRB1 and its associated transcriptional program are also expressed by substantial T cell populations in other human cancers. Our work provides an atlas of T cells in gliomas and highlights CD161 and other NK cell receptors as immunotherapy targets.

Published
2021

8. The Human Tumor Atlas Network: Charting Tumor Transitions across Space and Time at Single-Cell Resolution.

Author

Rozenblatt-Rosen, Orit, Regev, Aviv, Oberdoerffer, Philipp, Nawy, Tal, Hupalowska, Anna, Rood, Jennifer E, Ashenberg, Orr, Cerami, Ethan, Coffey, Robert J, Demir, Emek, Ding, Li, Esplin, Edward D, Ford, James M, Goecks, Jeremy, Ghosh, Sharmistha, Gray, Joe W, Guinney, Justin, Hanlon, Sean E, Hughes, Shannon K, Hwang, E Shelley, Iacobuzio-Donahue, Christine A, Jané-Valbuena, Judit, Johnson, Bruce E, Lau, Ken S, Lively, Tracy, Mazzilli, Sarah A, Pe'er, Dana, Santagata, Sandro, Shalek, Alex K, Schapiro, Denis, Snyder, Michael P, Sorger, Peter K, Spira, Avrum E, Srivastava, Sudhir, Tan, Kai, West, Robert B, Williams, Elizabeth H, and Human Tumor Atlas Network

Subjects
Human Tumor Atlas Network, Humans, Neoplasms, Cell Transformation, Neoplastic, Genomics, Atlases as Topic, Single-Cell Analysis, Tumor Microenvironment, Precision Medicine, AI, Cancer Moonshot, Human Tumor Atlas, cancer transitions, data integration, data visualization, metastasis, pre-cancer, resistance, single-cell genomics, spatial genomics, spatial imaging, tumor, Human Genome, Clinical Research, Genetics, Cancer, Bioengineering, 2.1 Biological and endogenous factors, Aetiology, Good Health and Well Being, Biological Sciences, Medical and Health Sciences, Developmental Biology
Abstract

Crucial transitions in cancer-including tumor initiation, local expansion, metastasis, and therapeutic resistance-involve complex interactions between cells within the dynamic tumor ecosystem. Transformative single-cell genomics technologies and spatial multiplex in situ methods now provide an opportunity to interrogate this complexity at unprecedented resolution. The Human Tumor Atlas Network (HTAN), part of the National Cancer Institute (NCI) Cancer Moonshot Initiative, will establish a clinical, experimental, computational, and organizational framework to generate informative and accessible three-dimensional atlases of cancer transitions for a diverse set of tumor types. This effort complements both ongoing efforts to map healthy organs and previous large-scale cancer genomics approaches focused on bulk sequencing at a single point in time. Generating single-cell, multiparametric, longitudinal atlases and integrating them with clinical outcomes should help identify novel predictive biomarkers and features as well as therapeutically relevant cell types, cell states, and cellular interactions across transitions. The resulting tumor atlases should have a profound impact on our understanding of cancer biology and have the potential to improve cancer detection, prevention, and therapeutic discovery for better precision-medicine treatments of cancer patients and those at risk for cancer.

Published
2020

10. Single-nucleus and spatial transcriptome profiling of pancreatic cancer identifies multicellular dynamics associated with neoadjuvant treatment

Author

Hwang, William L., Jagadeesh, Karthik A., Guo, Jimmy A., Hoffman, Hannah I., Yadollahpour, Payman, Reeves, Jason W., Mohan, Rahul, Drokhlyansky, Eugene, Van Wittenberghe, Nicholas, Ashenberg, Orr, Farhi, Samouil L., Schapiro, Denis, Divakar, Prajan, Miller, Eric, Zollinger, Daniel R., Eng, George, Schenkel, Jason M., Su, Jennifer, Shiau, Carina, Yu, Patrick, Freed-Pastor, William A., Abbondanza, Domenic, Mehta, Arnav, Gould, Joshua, Lambden, Conner, Porter, Caroline B. M., Tsankov, Alexander, Dionne, Danielle, Waldman, Julia, Cuoco, Michael S., Nguyen, Lan, Delorey, Toni, Phillips, Devan, Barth, Jaimie L., Kem, Marina, Rodrigues, Clifton, Ciprani, Debora, Roldan, Jorge, Zelga, Piotr, Jorgji, Vjola, Chen, Jonathan H., Ely, Zackery, Zhao, Daniel, Fuhrman, Kit, Fropf, Robin, Beechem, Joseph M., Loeffler, Jay S., Ryan, David P., Weekes, Colin D., Ferrone, Cristina R., Qadan, Motaz, Aryee, Martin J., Jain, Rakesh K., Neuberg, Donna S., Wo, Jennifer Y., Hong, Theodore S., Xavier, Ramnik, Aguirre, Andrew J., Rozenblatt-Rosen, Orit, Mino-Kenudson, Mari, Castillo, Carlos Fernandez-del, Liss, Andrew S., Ting, David T., Jacks, Tyler, and Regev, Aviv

Published
2022
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11. Author Correction: A single-cell atlas of human and mouse white adipose tissue

Author

Emont, Margo P., Jacobs, Christopher, Essene, Adam L., Pant, Deepti, Tenen, Danielle, Colleluori, Georgia, Di Vincenzo, Angelica, Jørgensen, Anja M., Dashti, Hesam, Stefek, Adam, McGonagle, Elizabeth, Strobel, Sophie, Laber, Samantha, Agrawal, Saaket, Westcott, Gregory P., Kar, Amrita, Veregge, Molly L., Gulko, Anton, Srinivasan, Harini, Kramer, Zachary, De Filippis, Eleanna, Merkel, Erin, Ducie, Jennifer, Boyd, Christopher G., Gourash, William, Courcoulas, Anita, Lin, Samuel J., Lee, Bernard T., Morris, Donald, Tobias, Adam, Khera, Amit V., Claussnitzer, Melina, Pers, Tune H., Giordano, Antonio, Ashenberg, Orr, Regev, Aviv, Tsai, Linus T., and Rosen, Evan D.

Published
2023
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12. A single-cell atlas of human and mouse white adipose tissue

Author

Emont, Margo P., Jacobs, Christopher, Essene, Adam L., Pant, Deepti, Tenen, Danielle, Colleluori, Georgia, Di Vincenzo, Angelica, Jørgensen, Anja M., Dashti, Hesam, Stefek, Adam, McGonagle, Elizabeth, Strobel, Sophie, Laber, Samantha, Agrawal, Saaket, Westcott, Gregory P., Kar, Amrita, Veregge, Molly L., Gulko, Anton, Srinivasan, Harini, Kramer, Zachary, De Filippis, Eleanna, Merkel, Erin, Ducie, Jennifer, Boyd, Christopher G., Gourash, William, Courcoulas, Anita, Lin, Samuel J., Lee, Bernard T., Morris, Donald, Tobias, Adam, Khera, Amit V., Claussnitzer, Melina, Pers, Tune H., Giordano, Antonio, Ashenberg, Orr, Regev, Aviv, Tsai, Linus T., and Rosen, Evan D.

Published
2022
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13. T Helper Cell Cytokines Modulate Intestinal Stem Cell Renewal and Differentiation.

Author

Chen, Zuojia, Wu, Chuan, Ordovas-Montanes, Jose, Alvarez, David, Herbst, Rebecca, Biton, Moshe, Haber, Adam, Rogel, Noga, Burgin, Grace, Beyaz, Semir, Schnell, Alexandra, Ashenberg, Orr, Su, Chien-Wen, Smillie, Christopher, Zhang, Mei, Tirosh, Itay, Dionne, Danielle, Nguyen, Lan, Xifaras, Michael, Shalek, Alex, von Andrian, Ulrich, Graham, Daniel, Rozenblatt-Rosen, Orit, Shi, Hai, Kuchroo, Vijay, Yilmaz, Omer, Regev, Aviv, Xavier, Ramnik, and Shekhar, Karthik

Subjects
ISCs, MHC class II, MHCII, T helper, T regulatory, T(reg), Th, epithelial differentiation, gut biology, intestinal stem cells, mucosal immunity, scRNA-seq, single cell RNA-seq, stem cell renewal, tuft cells, Animals, Cell Differentiation, Cell Self Renewal, Cytokines, Epithelial Cells, Female, Histocompatibility Antigens Class II, Immune System, Interleukin-10, Intestines, Male, Mice, Mice, Inbred C57BL, Organoids, Receptors, G-Protein-Coupled, Salmonella enterica, Stem Cells, T-Lymphocytes, Helper-Inducer
Abstract

In the small intestine, a niche of accessory cell types supports the generation of mature epithelial cell types from intestinal stem cells (ISCs). It is unclear, however, if and how immune cells in the niche affect ISC fate or the balance between self-renewal and differentiation. Here, we use single-cell RNA sequencing (scRNA-seq) to identify MHC class II (MHCII) machinery enrichment in two subsets of Lgr5+ ISCs. We show that MHCII+ Lgr5+ ISCs are non-conventional antigen-presenting cells in co-cultures with CD4+ T helper (Th) cells. Stimulation of intestinal organoids with key Th cytokines affects Lgr5+ ISC renewal and differentiation in opposing ways: pro-inflammatory signals promote differentiation, while regulatory cells and cytokines reduce it. In vivo genetic perturbation of Th cells or MHCII expression on Lgr5+ ISCs impacts epithelial cell differentiation and IEC fate during infection. These interactions between Th cells and Lgr5+ ISCs, thus, orchestrate tissue-wide responses to external signals.

Published
2018

14. T Helper Cell Cytokines Modulate Intestinal Stem Cell Renewal and Differentiation

Author

Biton, Moshe, Haber, Adam L, Rogel, Noga, Burgin, Grace, Beyaz, Semir, Schnell, Alexandra, Ashenberg, Orr, Su, Chien-Wen, Smillie, Christopher, Shekhar, Karthik, Chen, Zuojia, Wu, Chuan, Ordovas-Montanes, Jose, Alvarez, David, Herbst, Rebecca H, Zhang, Mei, Tirosh, Itay, Dionne, Danielle, Nguyen, Lan T, Xifaras, Michael E, Shalek, Alex K, von Andrian, Ulrich H, Graham, Daniel B, Rozenblatt-Rosen, Orit, Shi, Hai Ning, Kuchroo, Vijay, Yilmaz, Omer H, Regev, Aviv, and Xavier, Ramnik J

Subjects
Biodefense, Digestive Diseases, Regenerative Medicine, Stem Cell Research, Prevention, Vaccine Related, Stem Cell Research - Nonembryonic - Non-Human, 2.1 Biological and endogenous factors, Aetiology, Inflammatory and immune system, Animals, Cell Differentiation, Cell Self Renewal, Cytokines, Epithelial Cells, Female, Histocompatibility Antigens Class II, Immune System, Interleukin-10, Intestines, Male, Mice, Mice, Inbred C57BL, Organoids, Receptors, G-Protein-Coupled, Salmonella enterica, Stem Cells, T-Lymphocytes, Helper-Inducer, ISCs, MHC class II, MHCII, T helper, T regulatory, T(reg), Th, epithelial differentiation, gut biology, intestinal stem cells, mucosal immunity, scRNA-seq, single cell RNA-seq, stem cell renewal, tuft cells, Biological Sciences, Medical and Health Sciences, Developmental Biology
Abstract

In the small intestine, a niche of accessory cell types supports the generation of mature epithelial cell types from intestinal stem cells (ISCs). It is unclear, however, if and how immune cells in the niche affect ISC fate or the balance between self-renewal and differentiation. Here, we use single-cell RNA sequencing (scRNA-seq) to identify MHC class II (MHCII) machinery enrichment in two subsets of Lgr5+ ISCs. We show that MHCII+ Lgr5+ ISCs are non-conventional antigen-presenting cells in co-cultures with CD4+ T helper (Th) cells. Stimulation of intestinal organoids with key Th cytokines affects Lgr5+ ISC renewal and differentiation in opposing ways: pro-inflammatory signals promote differentiation, while regulatory cells and cytokines reduce it. In vivo genetic perturbation of Th cells or MHCII expression on Lgr5+ ISCs impacts epithelial cell differentiation and IEC fate during infection. These interactions between Th cells and Lgr5+ ISCs, thus, orchestrate tissue-wide responses to external signals.

Published
2018

15. Mouse fetal growth restriction through parental and fetal immune gene variation and intercellular communications cascade

Author

Kaur, Gurman, Porter, Caroline B. M., Ashenberg, Orr, Lee, Jack, Riesenfeld, Samantha J., Hofree, Matan, Aggelakopoulou, Maria, Subramanian, Ayshwarya, Kuttikkatte, Subita Balaram, Attfield, Kathrine E., Desel, Christiane A. E., Davies, Jessica L., Evans, Hayley G., Avraham-Davidi, Inbal, Nguyen, Lan T., Dionne, Danielle A., Neumann, Anna E., Jensen, Lise Torp, Barber, Thomas R., Soilleux, Elizabeth, Carrington, Mary, McVean, Gil, Rozenblatt-Rosen, Orit, Regev, Aviv, and Fugger, Lars

Published
2022
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16. Blood and immune development in human fetal bone marrow and Down syndrome

Author

Jardine, Laura, Webb, Simone, Goh, Issac, Quiroga Londoño, Mariana, Reynolds, Gary, Mather, Michael, Olabi, Bayanne, Stephenson, Emily, Botting, Rachel A., Horsfall, Dave, Engelbert, Justin, Maunder, Daniel, Mende, Nicole, Murnane, Caitlin, Dann, Emma, McGrath, Jim, King, Hamish, Kucinski, Iwo, Queen, Rachel, Carey, Christopher D., Shrubsole, Caroline, Poyner, Elizabeth, Acres, Meghan, Jones, Claire, Ness, Thomas, Coulthard, Rowen, Elliott, Natalina, O’Byrne, Sorcha, Haltalli, Myriam L. R., Lawrence, John E., Lisgo, Steven, Balogh, Petra, Meyer, Kerstin B., Prigmore, Elena, Ambridge, Kirsty, Jain, Mika Sarkin, Efremova, Mirjana, Pickard, Keir, Creasey, Thomas, Bacardit, Jaume, Henderson, Deborah, Coxhead, Jonathan, Filby, Andrew, Hussain, Rafiqul, Dixon, David, McDonald, David, Popescu, Dorin-Mirel, Kowalczyk, Monika S., Li, Bo, Ashenberg, Orr, Tabaka, Marcin, Dionne, Danielle, Tickle, Timothy L., Slyper, Michal, Rozenblatt-Rosen, Orit, Regev, Aviv, Behjati, Sam, Laurenti, Elisa, Wilson, Nicola K., Roy, Anindita, Göttgens, Berthold, Roberts, Irene, Teichmann, Sarah A., and Haniffa, Muzlifah

Published
2021
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17. COVID-19 tissue atlases reveal SARS-CoV-2 pathology and cellular targets

Author

Delorey, Toni M., Ziegler, Carly G. K., Heimberg, Graham, Normand, Rachelly, Yang, Yiming, Segerstolpe, Åsa, Abbondanza, Domenic, Fleming, Stephen J., Subramanian, Ayshwarya, Montoro, Daniel T., Jagadeesh, Karthik A., Dey, Kushal K., Sen, Pritha, Slyper, Michal, Pita-Juárez, Yered H., Phillips, Devan, Biermann, Jana, Bloom-Ackermann, Zohar, Barkas, Nikolaos, Ganna, Andrea, Gomez, James, Melms, Johannes C., Katsyv, Igor, Normandin, Erica, Naderi, Pourya, Popov, Yury V., Raju, Siddharth S., Niezen, Sebastian, Tsai, Linus T.-Y., Siddle, Katherine J., Sud, Malika, Tran, Victoria M., Vellarikkal, Shamsudheen K., Wang, Yiping, Amir-Zilberstein, Liat, Atri, Deepak S., Beechem, Joseph, Brook, Olga R., Chen, Jonathan, Divakar, Prajan, Dorceus, Phylicia, Engreitz, Jesse M., Essene, Adam, Fitzgerald, Donna M., Fropf, Robin, Gazal, Steven, Gould, Joshua, Grzyb, John, Harvey, Tyler, Hecht, Jonathan, Hether, Tyler, Jané-Valbuena, Judit, Leney-Greene, Michael, Ma, Hui, McCabe, Cristin, McLoughlin, Daniel E., Miller, Eric M., Muus, Christoph, Niemi, Mari, Padera, Robert, Pan, Liuliu, Pant, Deepti, Pe’er, Carmel, Pfiffner-Borges, Jenna, Pinto, Christopher J., Plaisted, Jacob, Reeves, Jason, Ross, Marty, Rudy, Melissa, Rueckert, Erroll H., Siciliano, Michelle, Sturm, Alexander, Todres, Ellen, Waghray, Avinash, Warren, Sarah, Zhang, Shuting, Zollinger, Daniel R., Cosimi, Lisa, Gupta, Rajat M., Hacohen, Nir, Hibshoosh, Hanina, Hide, Winston, Price, Alkes L., Rajagopal, Jayaraj, Tata, Purushothama Rao, Riedel, Stefan, Szabo, Gyongyi, Tickle, Timothy L., Ellinor, Patrick T., Hung, Deborah, Sabeti, Pardis C., Novak, Richard, Rogers, Robert, Ingber, Donald E., Jiang, Z. Gordon, Juric, Dejan, Babadi, Mehrtash, Farhi, Samouil L., Izar, Benjamin, Stone, James R., Vlachos, Ioannis S., Solomon, Isaac H., Ashenberg, Orr, Porter, Caroline B. M., Li, Bo, Shalek, Alex K., Villani, Alexandra-Chloé, Rozenblatt-Rosen, Orit, and Regev, Aviv

Published
2021
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18. A spatial cell atlas of neuroblastoma reveals developmental, epigenetic and spatial axis of tumor heterogeneity

Author

Patel, Anand G., primary, Ashenberg, Orr, additional, Collins, Natalie B., additional, Segerstolpe, Åsa, additional, Jiang, Sizun, additional, Slyper, Michal, additional, Huang, Xin, additional, Caraccio, Chiara, additional, Jin, Hongjian, additional, Sheppard, Heather, additional, Xu, Ke, additional, Chang, Ti-Cheng, additional, Orr, Brent A., additional, Shirinifard, Abbas, additional, Chapple, Richard H., additional, Shen, Amber, additional, Clay, Michael R., additional, Tatevossian, Ruth G., additional, Reilly, Colleen, additional, Patel, Jaimin, additional, Lupo, Marybeth, additional, Cline, Cynthia, additional, Dionne, Danielle, additional, Porter, Caroline B.M., additional, Waldman, Julia, additional, Bai, Yunhao, additional, Zhu, Bokai, additional, Barrera, Irving, additional, Murray, Evan, additional, Vigneau, Sébastien, additional, Napolitano, Sara, additional, Wakiro, Isaac, additional, Wu, Jingyi, additional, Grimaldi, Grace, additional, Dellostritto, Laura, additional, Helvie, Karla, additional, Rotem, Asaf, additional, Lako, Ana, additional, Cullen, Nicole, additional, Pfaff, Kathleen L., additional, Karlström, Åsa, additional, Jané-Valbuena, Judit, additional, Todres, Ellen, additional, Thorner, Aaron, additional, Geeleher, Paul, additional, Rodig, Scott J., additional, Zhou, Xin, additional, Stewart, Elizabeth, additional, Johnson, Bruce E., additional, Wu, Gang, additional, Chen, Fei, additional, Yu, Jiyang, additional, Goltsev, Yury, additional, Nolan, Garry P., additional, Rozenblatt-Rosen, Orit, additional, Regev, Aviv, additional, and Dyer, Michael A., additional

Published
2024
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19. A single-cell and single-nucleus RNA-Seq toolbox for fresh and frozen human tumors

Author

Slyper, Michal, Porter, Caroline B. M., Ashenberg, Orr, Waldman, Julia, Drokhlyansky, Eugene, Wakiro, Isaac, and Smillie, Christopher

Subjects
Tumors -- Identification and classification -- Usage, RNA sequencing -- Usage, Biological sciences, Health
Abstract

Single-cell genomics is essential to chart tumor ecosystems. Although single-cell RNA-Seq (scRNA-Seq) profiles RNA from cells dissociated from fresh tumors, single-nucleus RNA-Seq (snRNA-Seq) is needed to profile frozen or hard-to-dissociate tumors. Each requires customization to different tissue and tumor types, posing a barrier to adoption. Here, we have developed a systematic toolbox for profiling fresh and frozen clinical tumor samples using scRNA-Seq and snRNA-Seq, respectively. We analyzed 216,490 cells and nuclei from 40 samples across 23 specimens spanning eight tumor types of varying tissue and sample characteristics. We evaluated protocols by cell and nucleus quality, recovery rate and cellular composition. scRNA-Seq and snRNA-Seq from matched samples recovered the same cell types, but at different proportions. Our work provides guidance for studies in a broad range of tumors, including criteria for testing and selecting methods from the toolbox for other tumors, thus paving the way for charting tumor atlases. A set of ready-to-use tools for profiling fresh and frozen clinical tumor samples using scRNA-Seq and snRNA-Seq facilitates the implementation of single-cell technologies in clinical settings and the construction of single-cell tumor atlases., Author(s): Michal Slyper [sup.1] , Caroline B. M. Porter [sup.1] , Orr Ashenberg [sup.1] , Julia Waldman [sup.1] , Eugene Drokhlyansky [sup.1] , Isaac Wakiro [sup.2] [sup.3] [sup.4] , Christopher [...]

Published
2020
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20. A single-cell landscape of high-grade serous ovarian cancer

Author

Izar, Benjamin, Tirosh, Itay, Stover, Elizabeth H., Wakiro, Isaac, Cuoco, Michael S., Alter, Idan, Rodman, Christopher, Leeson, Rachel, Su, Mei-Ju, Shah, Parin, Iwanicki, Marcin, Walker, Sarah R., Kanodia, Abhay, Melms, Johannes C., Mei, Shaolin, Lin, Jia-Ren, Porter, Caroline B. M., Slyper, Michal, Waldman, Julia, Jerby-Arnon, Livnat, Ashenberg, Orr, Brinker, Titus J., Mills, Caitlin, Rogava, Meri, Vigneau, Sébastien, Sorger, Peter K., Garraway, Levi A., Konstantinopoulos, Panagiotis A., Liu, Joyce F., Matulonis, Ursula, Johnson, Bruce E., Rozenblatt-Rosen, Orit, Rotem, Asaf, and Regev, Aviv

Published
2020
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22. Robust protein-protein interactions in crowded cellular environments

Author

Deeds, Eric, Ashenberg, orr, Gerardine, Jaline, and Shakhnovich, Eugene

Subjects
Quantitative Biology - Biomolecules, Quantitative Biology - Molecular Networks
Abstract

The capacity of proteins to interact specifically with one another underlies our conceptual understanding of how living systems function. Systems-level study of specificity in protein-protein interactions is complicated by the fact that the cellular environment is crowded and heterogeneous; interaction pairs may exist at low relative concentrations and thus be presented with many more opportunities for promiscuous interactions compared to specific interaction possibilities. Here we address these questions using a simple computational model that includes specifically designed interacting model proteins immersed in a mixture containing hundreds of different unrelated ones; all of them undergo simulated diffusion and interaction. We find that specific complexes are quite robust to interference from promiscuous interaction partners, only in the range of temperatures Tdesign>T>Trand. At T>Tdesign specific complexes become unstable, while at TTrand. This condition requires an energy gap between binding energy in a specific complex and set of binding energies between randomly associating proteins, providing a general physical constraint on evolutionary selection or design of specific interacting protein interfaces. This work has implications for our understanding of how the protein repertoire functions and evolves within the context of cellular systems.

Published
2007
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23. A simple physical model for scaling in protein-protein interaction networks

Author

Deeds, Eric J., Ashenberg, Orr, and Shakhnovich, Eugene I.

Subjects
Quantitative Biology - Molecular Networks, Quantitative Biology - Biomolecules
Abstract

It has recently been demonstrated that many biological networks exhibit a scale-free topology where the probability of observing a node with a certain number of edges (k) follows a power law: i.e. p(k) ~ k^-g. This observation has been reproduced by evolutionary models. Here we consider the network of protein-protein interactions and demonstrate that two published independent measurements of these interactions produce graphs that are only weakly correlated with one another despite their strikingly similar topology. We then propose a physical model based on the fundamental principle that (de)solvation is a major physical factor in protein-protein interactions. This model reproduces not only the scale-free nature of such graphs but also a number of higher-order correlations in these networks. A key support of the model is provided by the discovery of a significant correlation between number of interactions made by a protein and the fraction of hydrophobic residues on its surface. The model presented in this paper represents the first physical model for experimentally determined protein-protein interactions that comprehensively reproduces the topological features of interaction networks. These results have profound implications for understanding not only protein-protein interactions but also other types of scale-free networks., Comment: 50 pages, 17 figures

Published
2005
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24. Decoding human fetal liver haematopoiesis

Author

Popescu, Dorin-Mirel, Botting, Rachel A., Stephenson, Emily, Green, Kile, Webb, Simone, Jardine, Laura, Calderbank, Emily F., Polanski, Krzysztof, Goh, Issac, Efremova, Mirjana, Acres, Meghan, Maunder, Daniel, Vegh, Peter, Gitton, Yorick, Park, Jong-Eun, Vento-Tormo, Roser, Miao, Zhichao, Dixon, David, Rowell, Rachel, McDonald, David, Fletcher, James, Poyner, Elizabeth, Reynolds, Gary, Mather, Michael, Moldovan, Corina, Mamanova, Lira, Greig, Frankie, Young, Matthew D., Meyer, Kerstin B., Lisgo, Steven, Bacardit, Jaume, Fuller, Andrew, Millar, Ben, Innes, Barbara, Lindsay, Susan, Stubbington, Michael J. T., Kowalczyk, Monika S., Li, Bo, Ashenberg, Orr, Tabaka, Marcin, Dionne, Danielle, Tickle, Timothy L., Slyper, Michal, Rozenblatt-Rosen, Orit, Filby, Andrew, Carey, Peter, Villani, Alexandra-Chloé, Roy, Anindita, Regev, Aviv, Chédotal, Alain, Roberts, Irene, Göttgens, Berthold, Behjati, Sam, Laurenti, Elisa, Teichmann, Sarah A., and Haniffa, Muzlifah

Published
2019
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25. A cellular and spatial atlas ofTP53-associated tissue remodeling in lung adenocarcinoma

Author

Zhao, William, primary, Kepecs, Benjamin, additional, Mahadevan, Navin R., additional, Segerstolpe, Asa, additional, Weirather, Jason L., additional, Besson, Naomi R., additional, Giotti, Bruno, additional, Soong, Brian Y., additional, Li, Chendi, additional, Vigneau, Sebastien, additional, Slyper, Michal, additional, Wakiro, Isaac, additional, Jane-Valbuena, Judit, additional, Ashenberg, Orr, additional, Rotem, Asaf, additional, Bueno, Raphael, additional, Rozenblatt-Rosen, Orit, additional, Pfaff, Kathleen, additional, Rodig, Scott, additional, Hata, Aaron N., additional, Regev, Aviv, additional, Johnson, Bruce E., additional, and Tsankov, Alexander M., additional

Published
2023
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26. Single-nucleus cross-tissue molecular reference maps toward understanding disease gene function

Author

Massachusetts Institute of Technology. Department of Biology, Eraslan, Gökcen, Drokhlyansky, Eugene, Anand, Shankara, Fiskin, Evgenij, Subramanian, Ayshwarya, Slyper, Michal, Wang, Jiali, Van Wittenberghe, Nicholas, Rouhana, John M, Waldman, Julia, Ashenberg, Orr, Lek, Monkol, Dionne, Danielle, Win, Thet Su, Cuoco, Michael S, Kuksenko, Olena, Tsankov, Alexander M, Branton, Philip A, Marshall, Jamie L, Greka, Anna, Getz, Gad, Segrè, Ayellet V, Aguet, François, Rozenblatt-Rosen, Orit, Ardlie, Kristin G, Regev, Aviv, Massachusetts Institute of Technology. Department of Biology, Eraslan, Gökcen, Drokhlyansky, Eugene, Anand, Shankara, Fiskin, Evgenij, Subramanian, Ayshwarya, Slyper, Michal, Wang, Jiali, Van Wittenberghe, Nicholas, Rouhana, John M, Waldman, Julia, Ashenberg, Orr, Lek, Monkol, Dionne, Danielle, Win, Thet Su, Cuoco, Michael S, Kuksenko, Olena, Tsankov, Alexander M, Branton, Philip A, Marshall, Jamie L, Greka, Anna, Getz, Gad, Segrè, Ayellet V, Aguet, François, Rozenblatt-Rosen, Orit, Ardlie, Kristin G, and Regev, Aviv

Abstract

Understanding gene function and regulation in homeostasis and disease requires knowledge of the cellular and tissue contexts in which genes are expressed. Here, we applied four single-nucleus RNA sequencing methods to eight diverse, archived, frozen tissue types from 16 donors and 25 samples, generating a cross-tissue atlas of 209,126 nuclei profiles, which we integrated across tissues, donors, and laboratory methods with a conditional variational autoencoder. Using the resulting cross-tissue atlas, we highlight shared and tissue-specific features of tissue-resident cell populations; identify cell types that might contribute to neuromuscular, metabolic, and immune components of monogenic diseases and the biological processes involved in their pathology; and determine cell types and gene modules that might underlie disease mechanisms for complex traits analyzed by genome-wide association studies.

Published
2023

27. Author Correction: A single-cell and single-nucleus RNA-Seq toolbox for fresh and frozen human tumors

Author

Slyper, Michal, Porter, Caroline B. M., Ashenberg, Orr, Waldman, Julia, Drokhlyansky, Eugene, Wakiro, Isaac, Smillie, Christopher, Smith-Rosario, Gabriela, Wu, Jingyi, Dionne, Danielle, Vigneau, Sébastien, Jané-Valbuena, Judit, Tickle, Timothy L., Napolitano, Sara, Su, Mei-Ju, Patel, Anand G., Karlstrom, Asa, Gritsch, Simon, Nomura, Masashi, Waghray, Avinash, Gohil, Satyen H., Tsankov, Alexander M., Jerby-Arnon, Livnat, Cohen, Ofir, Klughammer, Johanna, Rosen, Yanay, Gould, Joshua, Nguyen, Lan, Hofree, Matan, Tramontozzi, Peter J., Li, Bo, Wu, Catherine J., Izar, Benjamin, Haq, Rizwan, Hodi, F. Stephen, Yoon, Charles H., Hata, Aaron N., Baker, Suzanne J., Suvà, Mario L., Bueno, Raphael, Stover, Elizabeth H., Clay, Michael R., Dyer, Michael A., Collins, Natalie B., Matulonis, Ursula A., Wagle, Nikhil, Johnson, Bruce E., Rotem, Asaf, Rozenblatt-Rosen, Orit, and Regev, Aviv

Published
2020
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28. SlideCNA: Spatial copy number alteration detection from Slide-seq-like spatial transcriptomics data

Author

Zhang, Diane, primary, Segerstolpe, Asa, additional, Slyper, Michal, additional, Waldman, Julia, additional, Murray, Evan, additional, Cohen, Ofir, additional, Ashenberg, Orr, additional, Abravanel, Daniel, additional, Jané-Valbuena, Judit, additional, Mages, Simon, additional, Lako, Ana, additional, Helvie, Karla, additional, Rozenblatt-Rosen, Orit, additional, Rodig, Scott, additional, Chen, Fei, additional, Wagle, Nikhil, additional, Regev, Aviv, additional, and Klughammer, Johanna, additional

Published
2022
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29. Abstract C012: Dissecting the reorganization of pancreatic tumor microenvironments after radiation and immunotherapy reveals insights into immunotherapy resistance

Author

Mehta, Arnav, primary, Parikh, Aparna, additional, Parikh, Milan, additional, Park, Ryan, additional, Sade-Feldman, Moshe, additional, Bi, Lynn, additional, Carzo, Nicole, additional, Grillo, Tarin M., additional, Baiev, Islam, additional, Asupoto, Olanike, additional, Gushterova, Irena, additional, LaSalle, Tom, additional, Gonye, Anna, additional, Blaum, Emily, additional, Vigneau, Sebastien, additional, Chaligne, Ronan, additional, Lako, Ana, additional, Lila, Thomas, additional, Nelson, David, additional, Porter, Caroline, additional, Ashenberg, Orr, additional, Jagadesh, Karthik, additional, Hwang, William L., additional, Smillie, Christopher, additional, Ryan, David P., additional, Ting, David T., additional, Hong, Theodore, additional, Pe'er, Dana, additional, and Hacohen, Nir, additional

Published
2022
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30. A single-nucleus and spatial transcriptomic atlas of the COVID-19 liver reveals topological, functional, and regenerative organ disruption in patients

Author

Pita-Juarez, Yered, primary, Karagkouni, Dimitra, additional, Kalavros, Nikolaos, additional, Melms, Johannes C., additional, Niezen, Sebastian, additional, Delorey, Toni M., additional, Essene, Adam L, additional, Brook, Olga R., additional, Pant, Deepti, additional, Skelton-Badlani, Disha, additional, Naderi, Pourya, additional, Huang, Pinzhu, additional, Pan, Liuliu, additional, Hether, Tyler, additional, Andrews, Tallulah S., additional, Ziegler, Carly G.K., additional, Reeves, Jason, additional, Myloserdnyy, Andriy, additional, Chen, Rachel, additional, Nam, Andy, additional, Phelan, Stefan, additional, Liang, Yan, additional, Amin, Amit Dipak, additional, Biermann, Jana, additional, Hibshoosh, Hanina, additional, Veregge, Molly, additional, Kramer, Zachary, additional, Jacobs, Christopher, additional, Yalcin, Yusuf, additional, Phillips, Devan, additional, Slyper, Michal, additional, Subramanian, Ayshwarya, additional, Ashenberg, Orr, additional, Bloom-Ackermann, Zohar, additional, Tran, Victoria M., additional, Gomez, James, additional, Sturm, Alexander, additional, Zhang, Shuting, additional, Fleming, Stephen J., additional, Warren, Sarah, additional, Beechem, Joseph, additional, Hung, Deborah, additional, Babadi, Mehrtash, additional, Padera, Robert F., additional, MacParland, Sonya A., additional, Bader, Gary D., additional, Imad, Nasser, additional, Solomon, Isaac H., additional, Miller, Eric, additional, Riedel, Stefan, additional, Porter, Caroline B.M., additional, Villani, Alexandra-Chloé, additional, Tsai, Linus T.-Y., additional, Hide, Winston, additional, Szabo, Gyongyi, additional, Hecht, Jonathan, additional, Rozenblatt-Rosen, Orit, additional, Shalek, Alex K., additional, Izar, Benjamin, additional, Regev, Aviv, additional, Popov, Yury, additional, Jiang, Z. Gordon, additional, and Vlachos, Ioannis S., additional

Published
2022
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31. Tissue-resident memory and circulating T cells are early responders to pre-surgical cancer immunotherapy

Author

Luoma, Adrienne M., primary, Suo, Shengbao, additional, Wang, Yifan, additional, Gunasti, Lauren, additional, Porter, Caroline B.M., additional, Nabilsi, Nancy, additional, Tadros, Jenny, additional, Ferretti, Andrew P., additional, Liao, Sida, additional, Gurer, Cagan, additional, Chen, Yu-Hui, additional, Criscitiello, Shana, additional, Ricker, Cora A., additional, Dionne, Danielle, additional, Rozenblatt-Rosen, Orit, additional, Uppaluri, Ravindra, additional, Haddad, Robert I., additional, Ashenberg, Orr, additional, Regev, Aviv, additional, Van Allen, Eliezer M., additional, MacBeath, Gavin, additional, Schoenfeld, Jonathan D., additional, and Wucherpfennig, Kai W., additional

Published
2022
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34. Emergence of a High-Plasticity Cell State during Lung Cancer Evolution

Author

Marjanovic, Nemanja Despot, Hofree, Matan, Chan, Jason E., Canner, David, Wu, Katherine, Trakala, Marianna, Hartmann, Griffin G., Smith, Olivia C., Kim, Jonathan Y., Evans, Kelly Victoria, Hudson, Anna, Ashenberg, Orr, Porter, Caroline B.M., Bejnood, Alborz, Subramanian, Ayshwarya, Pitter, Kenneth, Yan, Yan, Delorey, Toni, Phillips, Devan R., Shah, Nisargbhai, Chaudhary, Ojasvi, Tsankov, Alexander, Hollmann, Travis, Rekhtman, Natasha, Massion, Pierre P., Poirier, John T., Mazutis, Linas, Li, Ruifang, Lee, Joo-Hyeon, Amon, Angelika, Rudin, Charles M., Jacks, Tyler, Regev, Aviv, Tammela, Tuomas, Marjanovic, Nemanja Despot, Hofree, Matan, Chan, Jason E., Canner, David, Wu, Katherine, Trakala, Marianna, Hartmann, Griffin G., Smith, Olivia C., Kim, Jonathan Y., Evans, Kelly Victoria, Hudson, Anna, Ashenberg, Orr, Porter, Caroline B.M., Bejnood, Alborz, Subramanian, Ayshwarya, Pitter, Kenneth, Yan, Yan, Delorey, Toni, Phillips, Devan R., Shah, Nisargbhai, Chaudhary, Ojasvi, Tsankov, Alexander, Hollmann, Travis, Rekhtman, Natasha, Massion, Pierre P., Poirier, John T., Mazutis, Linas, Li, Ruifang, Lee, Joo-Hyeon, Amon, Angelika, Rudin, Charles M., Jacks, Tyler, Regev, Aviv, and Tammela, Tuomas

Abstract

Tumor evolution from a single cell into a malignant, heterogeneous tissue remains poorly understood. Here, we profile single-cell transcriptomes of genetically engineered mouse lung tumors at seven stages, from pre-neoplastic hyperplasia to adenocarcinoma. The diversity of transcriptional states increases over time and is reproducible across tumors and mice. Cancer cells progressively adopt alternate lineage identities, computationally predicted to be mediated through a common transitional, high-plasticity cell state (HPCS). Accordingly, HPCS cells prospectively isolated from mouse tumors and human patient-derived xenografts display high capacity for differentiation and proliferation. The HPCS program is associated with poor survival across human cancers and demonstrates chemoresistance in mice. Our study reveals a central principle underpinning intra-tumoral heterogeneity and motivates therapeutic targeting of the HPCS. Cellular states capable of promoting tumor progression and resisting therapies exist in heterogeneous tumors. Marjanovic et al. discover that a high-plasticity cell state common to mouse and human lung tumors drives cellular heterogeneity, is highly tumorigenic and drug resistant, and associates with poor patient prognosis.

Published
2022

35. A single-cell landscape of high-grade serous ovarian cancer

Author

Izar, Benjamin, Tirosh, Itay, Stover, Elizabeth H., Wakiro, Isaac, Cuoco, Michael S., Alter, Idan, Rodman, Christopher, Leeson, Rachel, Su, Mei-Ju, Shah, Parin, Iwanicki, Marcin, Walker, Sarah R., Kanodia, Abhay, Melms, Johannes C., Mei, Shaolin, Lin, Jia-Ren, Porter, Caroline B. M., Slyper, Michal, Waldman, Julia, Jerby-Arnon, Livnat, Ashenberg, Orr, Brinker, Titus J., Mills, Caitlin, Rogava, Meri, Vigneau, Sébastien, Sorger, Peter K., Garraway, Levi A., Konstantinopoulos, Panagiotis A., Liu, Joyce F., Matulonis, Ursula, Johnson, Bruce E., Rozenblatt-Rosen, Orit, Rotem, Asaf, Regev, Aviv, Izar, Benjamin, Tirosh, Itay, Stover, Elizabeth H., Wakiro, Isaac, Cuoco, Michael S., Alter, Idan, Rodman, Christopher, Leeson, Rachel, Su, Mei-Ju, Shah, Parin, Iwanicki, Marcin, Walker, Sarah R., Kanodia, Abhay, Melms, Johannes C., Mei, Shaolin, Lin, Jia-Ren, Porter, Caroline B. M., Slyper, Michal, Waldman, Julia, Jerby-Arnon, Livnat, Ashenberg, Orr, Brinker, Titus J., Mills, Caitlin, Rogava, Meri, Vigneau, Sébastien, Sorger, Peter K., Garraway, Levi A., Konstantinopoulos, Panagiotis A., Liu, Joyce F., Matulonis, Ursula, Johnson, Bruce E., Rozenblatt-Rosen, Orit, Rotem, Asaf, and Regev, Aviv

Abstract

© 2020, The Author(s), under exclusive licence to Springer Nature America, Inc. Malignant abdominal fluid (ascites) frequently develops in women with advanced high-grade serous ovarian cancer (HGSOC) and is associated with drug resistance and a poor prognosis1. To comprehensively characterize the HGSOC ascites ecosystem, we used single-cell RNA sequencing to profile ~11,000 cells from 22 ascites specimens from 11 patients with HGSOC. We found significant inter-patient variability in the composition and functional programs of ascites cells, including immunomodulatory fibroblast sub-populations and dichotomous macrophage populations. We found that the previously described immunoreactive and mesenchymal subtypes of HGSOC, which have prognostic implications, reflect the abundance of immune infiltrates and fibroblasts rather than distinct subsets of malignant cells2. Malignant cell variability was partly explained by heterogeneous copy number alteration patterns or expression of a stemness program. Malignant cells shared expression of inflammatory programs that were largely recapitulated in single-cell RNA sequencing of ~35,000 cells from additionally collected samples, including three ascites, two primary HGSOC tumors and three patient ascites-derived xenograft models. Inhibition of the JAK/STAT pathway, which was expressed in both malignant cells and cancer-associated fibroblasts, had potent anti-tumor activity in primary short-term cultures and patient-derived xenograft models. Our work contributes to resolving the HSGOC landscape3–5 and provides a resource for the development of novel therapeutic approaches.

Published
2022

36. Single-nucleus cross-tissue molecular reference maps toward understanding disease gene function

Author

Eraslan, Gökcen, primary, Drokhlyansky, Eugene, additional, Anand, Shankara, additional, Fiskin, Evgenij, additional, Subramanian, Ayshwarya, additional, Slyper, Michal, additional, Wang, Jiali, additional, Van Wittenberghe, Nicholas, additional, Rouhana, John M., additional, Waldman, Julia, additional, Ashenberg, Orr, additional, Lek, Monkol, additional, Dionne, Danielle, additional, Win, Thet Su, additional, Cuoco, Michael S., additional, Kuksenko, Olena, additional, Tsankov, Alexander M., additional, Branton, Philip A., additional, Marshall, Jamie L., additional, Greka, Anna, additional, Getz, Gad, additional, Segrè, Ayellet V., additional, Aguet, François, additional, Rozenblatt-Rosen, Orit, additional, Ardlie, Kristin G., additional, and Regev, Aviv, additional

Published
2022
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38. Abstract PD6-03: Spatio-molecular dissection of the breast cancer metastatic microenvironment

Author

Abravanel, Daniel L, primary, Klughammer, Johanna, additional, Blosser, Timothy, additional, Goltsev, Yury, additional, Jiang, Sizun, additional, Bai, Yunjao, additional, Murray, Evan, additional, Alon, Shahar, additional, Cui, Yi, additional, Goodwin, Daniel R, additional, Sinha, Anubhav, additional, Cohen, Ofir, additional, Slyper, Michal, additional, Ashenberg, Orr, additional, Dionne, Danielle, additional, Jané-Valbuena, Judit, additional, Porter, Caroline BM, additional, Segerstolpe, Asa, additional, Waldman, Julia, additional, Vigneau, Sébastien, additional, Helvie, Karla, additional, Frangieh, Allison, additional, DelloStritto, Laura, additional, Patel, Miraj, additional, We, Jingyi, additional, Pfaff, Kathleen, additional, Cullen, Nicole, additional, Lako, Ana, additional, Turner, Madison, additional, Wakiro, Isaac, additional, Napolitano, Sara, additional, Kanodia, Abhay, additional, Ortiz, Rebecca, additional, MacKichan, Colin, additional, Inga, Stephanie, additional, Chen, Judy, additional, Thorner, Aaron R, additional, Rotem, Asaf, additional, Rodig, Scott, additional, Chen, Fei, additional, Boyden, Edward S, additional, Nolan, Garry P, additional, Zhuang, Xiaowei, additional, Rozenblatt-Rosen, Orit, additional, Johnson, Bruce E, additional, Regev, Aviv, additional, and Wagle, Nikhil, additional

Published
2022
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40. A single cell atlas of human and mouse white adipose tissue

Author

Emont, Margo P, primary, Jacobs, Christopher, additional, Essene, Adam L, additional, Pant, Deepti, additional, Tenen, Danielle, additional, Colleluori, Georgia, additional, De Vincenzo, Angelica, additional, Jørgensen, Anja M, additional, Dashti, Hesam, additional, Stefek, Adam, additional, McGonagle, Elizabeth, additional, Strobel, Sophie, additional, Laber, Samantha, additional, Agrawal, Saaket, additional, Westcott, Gregory P, additional, Kar, Amrita, additional, Veregge, Molly L, additional, Gulko, Anton, additional, Srinivasan, Harini, additional, Kramer, Zachary, additional, De Filippis, Eleanna, additional, Merkel, Erin, additional, Ducie, Jennifer, additional, Boyd, Christopher G, additional, Gourash, William, additional, Courcoulas, Anita, additional, Lin, Samuel J., additional, Lee, Bernard T, additional, Morris, Donald, additional, Tobias, Adam, additional, Khera, Amit V, additional, Claussnitzer, Melina, additional, Pers, Tune H., additional, Giordano, Antonio, additional, Ashenberg, Orr, additional, Regev, Aviv, additional, Tsai, Linus T, additional, and Rosen, Evan D, additional

Published
2021
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42. Single-nucleus cross-tissue molecular reference maps to decipher disease gene function

Author

Eraslan, Gokcen, primary, Drokhlyansky, Eugene, additional, Anand, Shankara, additional, Subramanian, Ayshwarya, additional, Fiskin, Evgenij, additional, Slyper, Michal, additional, Wang, Jiali, additional, Wittenberghe, Nicholas Van, additional, Rouhana, John M., additional, Waldman, Julia, additional, Ashenberg, Orr, additional, Dionne, Danielle, additional, Win, Thet Su, additional, Cuoco, Michael S., additional, Kuksenko, Olena, additional, Branton, Philip A., additional, Marshall, Jamie L., additional, Greka, Anna, additional, Getz, Gad, additional, Segrè, Ayellet V., additional, Aguet, François, additional, Rozenblatt-Rosen, Orit, additional, Ardlie, Kristin G., additional, and Regev, Aviv, additional

Published
2021
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44. Abstract 94: Multi-compartment reprogramming and spatially-resolved interactions in frozen pancreatic cancer with and without neoadjuvant chemotherapy and radiotherapy at single-cell resolution

Author

Hwang, William L., primary, Jagadeesh, Karthik A., additional, Guo, Jimmy A., additional, Hoffman, Hannah I., additional, Yadollahpour, Payman, additional, Reeves, Jason, additional, Drokhlyansky, Eugene, additional, Van Wittenberghe, Nicholas, additional, Farhi, Samouil, additional, Schapiro, Denis, additional, Eng, George, additional, Schenkel, Jason M., additional, Freed-Pastor, William A., additional, Ashenberg, Orr, additional, Rodrigues, Clifton, additional, Abbondanza, Domenic, additional, Delorey, Toni, additional, Phillips, Devan, additional, Roldan, Jorge, additional, Ciprani, Debora, additional, Kern, Marina, additional, Barth, Jaimie L., additional, Zollinger, Daniel R., additional, Fuhrman, Kit, additional, Fropf, Robin, additional, Beechem, Joseph, additional, Weekes, Colin, additional, Ferrone, Cristina R., additional, Wo, Jennifer Y., additional, Hong, Theodore S., additional, Rozenblatt-Rosen, Orit, additional, Aguirre, Andrew J., additional, Mino-Kenudson, Mari, additional, Fernandez-del- Castillo, Carlos, additional, Liss, Andrew S., additional, Ting, David T., additional, Jacks, Tyler, additional, and Regev, Aviv, additional

Published
2021
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45. Cumulus provides cloud-based data analysis for large-scale single-cell and single-nucleus RNA-seq

Author

Koch Institute for Integrative Cancer Research at MIT, Massachusetts Institute of Technology. Department of Biology, Howard Hughes Medical Institute, Li, Bo, Gould, Joshua, Yang, Yiming, Sarkizova, Siranush, Tabaka, Marcin, Ashenberg, Orr, Rosen, Yanay, Slyper, Michal, Kowalczyk, Monika S, Villani, Alexandra-Chloé, Tickle, Timothy, Hacohen, Nir, Rozenblatt-Rosen, Orit, Regev, Aviv, Koch Institute for Integrative Cancer Research at MIT, Massachusetts Institute of Technology. Department of Biology, Howard Hughes Medical Institute, Li, Bo, Gould, Joshua, Yang, Yiming, Sarkizova, Siranush, Tabaka, Marcin, Ashenberg, Orr, Rosen, Yanay, Slyper, Michal, Kowalczyk, Monika S, Villani, Alexandra-Chloé, Tickle, Timothy, Hacohen, Nir, Rozenblatt-Rosen, Orit, and Regev, Aviv

Abstract

© 2020, The Author(s), under exclusive licence to Springer Nature America, Inc. Massively parallel single-cell and single-nucleus RNA sequencing has opened the way to systematic tissue atlases in health and disease, but as the scale of data generation is growing, so is the need for computational pipelines for scaled analysis. Here we developed Cumulus—a cloud-based framework for analyzing large-scale single-cell and single-nucleus RNA sequencing datasets. Cumulus combines the power of cloud computing with improvements in algorithm and implementation to achieve high scalability, low cost, user-friendliness and integrated support for a comprehensive set of features. We benchmark Cumulus on the Human Cell Atlas Census of Immune Cells dataset of bone marrow cells and show that it substantially improves efficiency over conventional frameworks, while maintaining or improving the quality of results, enabling large-scale studies.

Published
2021

47. Intrinsic and extrinsic regulation of human fetal bone marrow haematopoiesis and perturbations in Down syndrome

Author

Jardine, Laura, primary, Webb, Simone, additional, Goh, Issac, additional, Londoño, Mariana Quiroga, additional, Reynolds, Gary, additional, Mather, Michael, additional, Olabi, Bayanne, additional, Stephenson, Emily, additional, Botting, Rachel A., additional, Horsfall, Dave, additional, Engelbert, Justin, additional, Maunder, Daniel, additional, Mende, Nicole, additional, Murnane, Caitlin, additional, Dann, Emma, additional, McGrath, Jim, additional, King, Hamish, additional, Kucinski, Iwo, additional, Queen, Rachel, additional, Carey, Christopher D, additional, Shrubsole, Caroline, additional, Poyner, Elizabeth, additional, Acres, Meghan, additional, Jones, Claire, additional, Ness, Thomas, additional, Coulthard, Rowan, additional, Elliott, Natalina, additional, O’Byrne, Sorcha, additional, Haltalli, Myriam L. R., additional, Lawrence, John E, additional, Lisgo, Steven, additional, Balogh, Petra, additional, Meyer, Kerstin B, additional, Prigmore, Elena, additional, Ambridge, Kirsty, additional, Jain, Mika Sarkin, additional, Efremova, Mirjana, additional, Pickard, Keir, additional, Creasey, Thomas, additional, Bacardit, Jaume, additional, Henderson, Deborah, additional, Coxhead, Jonathan, additional, Filby, Andrew, additional, Hussain, Rafiqul, additional, Dixon, David, additional, McDonald, David, additional, Popescu, Dorin-Mirel, additional, Kowalczyk, Monika S., additional, Li, Bo, additional, Ashenberg, Orr, additional, Tabaka, Marcin, additional, Dionne, Danielle, additional, Tickle, Timothy L., additional, Slyper, Michal, additional, Rozenblatt-Rosen, Orit, additional, Regev, Aviv, additional, Behjati, Sam, additional, Laurenti, Elisa, additional, Wilson, Nicola K., additional, Roy, Anindita, additional, Göttgens, Berthold, additional, Roberts, Irene, additional, Teichmann, Sarah A., additional, and Haniffa, Muzlifah, additional

Published
2021
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48. Rewiring the Specificity of Two-Component Signal Transduction Systems

Author

Skerker, Jeffrey M., Perchuk, Barrett S., Siryaporn, Albert, Lubin, Emma A., Ashenberg, Orr, Goulian, Mark, and Laub, Michael T.

Subjects
Biological sciences
Abstract

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.cell.2008.04.040 Byline: Jeffrey M. Skerker (1), Barrett S. Perchuk (1), Albert Siryaporn (2), Emma A. Lubin (1), Orr Ashenberg (1), Mark Goulian (2)(3), Michael T. Laub (1) Keywords: SIGNALING; MICROBIO Abstract: Two-component signal transduction systems are the predominant means by which bacteria sense and respond to environmental stimuli. Bacteria often employ tens or hundreds of these paralogous signaling systems, comprised of histidine kinases (HKs) and their cognate response regulators (RRs). Faithful transmission of information through these signaling pathways and avoidance of detrimental crosstalk demand exquisite specificity of HK-RR interactions. To identify the determinants of two-component signaling specificity, we examined patterns of amino acid coevolution in large, multiple sequence alignments of cognate kinase-regulator pairs. Guided by these results, we demonstrate that a subset of the coevolving residues is sufficient, when mutated, to completely switch the substrate specificity of the kinase EnvZ. Our results shed light on the basis of molecular discrimination in two-component signaling pathways, provide a general approach for the rational rewiring of these pathways, and suggest that analyses of coevolution may facilitate the reprogramming of other signaling systems and protein-protein interactions. Author Affiliation: (1) Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA (2) Department of Physics, University of Pennsylvania, Philadelphia, PA 19104, USA (3) Department of Biology, University of Pennsylvania, Philadelphia, PA 19104, USA Article History: Received 7 February 2008; Revised 4 April 2008; Accepted 15 April 2008 Article Note: (miscellaneous) Published: June 12, 2008

Published
2008

49. Robust protein-protein interactions in crowded cellular environments

Author

Deeds, Eric J., Ashenberg, Orr, Gerardin, Jaline, and Shakhnovich, Eugene I.

Subjects
Protein-protein interactions -- Evaluation, Cellular control mechanisms -- Evaluation, Science and technology
Abstract

The capacity of proteins to interact specifically with one another underlies our conceptual understanding of how living systems function. Systems-level study of specificity in protein-protein interactions is complicated by the fact that the cellular environment is crowded and heterogeneous; interaction pairs may exist at low relative concentrations and thus be presented with many more opportunities for promiscuous interactions compared with specific interaction possibilities. Here we address these questions by using a simple computational model that includes specifically designed interacting model proteins immersed in a mixture containing hundreds of different unrelated ones; all of them undergo simulated diffusion and interaction. We find that specific complexes are quite robust to interference from promiscuous interaction partners only in the range of temperatures [T.sub.design] > T > [T.sub.rand]. At T > [T.sub.design], specific complexes become unstable, whereas at T < [T.sub.rand], formation of specific complexes is suppressed by promiscuous interactions. Specific interactions can form only if [T.sub.design] > [T.sub.rand]. This condition requires an energy gap between binding energy in a specific complex and set of binding energies between randomly associating proteins, providing a general physical constraint on evolutionary selection or design of specific interacting protein interfaces. This work has implications for our understanding of how the protein repertoire functions and evolves within the context of cellular systems. crowded cell environment | promiscuous interactions | specific interactions

Published
2007

50. A Cellular Taxonomy of the Bone Marrow Stroma in Homeostasis and Leukemia

Author

Massachusetts Institute of Technology. Department of Biology, Baryawno, Ninib, Przybylski, Dariusz, Kowalczyk, Monika S., Kfoury, Youmna, Severe, Nicolas, Gustafsson, Karin, Kokkaliaris, Konstantinos D., Mercier, Francois, Tabaka, Marcin, Hofree, Matan, Dionne, Danielle, Papazian, Ani, Lee, Dongjun, Ashenberg, Orr, Subramanian, Ayshwarya, Vaishnav, Eeshit Dhaval, Rozenblatt-Rosen, Orit, Regev, Aviv, Scadden, David T., Massachusetts Institute of Technology. Department of Biology, Baryawno, Ninib, Przybylski, Dariusz, Kowalczyk, Monika S., Kfoury, Youmna, Severe, Nicolas, Gustafsson, Karin, Kokkaliaris, Konstantinos D., Mercier, Francois, Tabaka, Marcin, Hofree, Matan, Dionne, Danielle, Papazian, Ani, Lee, Dongjun, Ashenberg, Orr, Subramanian, Ayshwarya, Vaishnav, Eeshit Dhaval, Rozenblatt-Rosen, Orit, Regev, Aviv, and Scadden, David T.

Abstract

Stroma is a poorly defined non-parenchymal component of virtually every organ with key roles in organ development, homeostasis, and repair. Studies of the bone marrow stroma have defined individual populations in the stem cell niche regulating hematopoietic regeneration and capable of initiating leukemia. Here, we use single-cell RNA sequencing (scRNA-seq) to define a cellular taxonomy of the mouse bone marrow stroma and its perturbation by malignancy. We identified seventeen stromal subsets expressing distinct hematopoietic regulatory genes spanning new fibroblastic and osteoblastic subpopulations including distinct osteoblast differentiation trajectories. Emerging acute myeloid leukemia impaired mesenchymal osteogenic differentiation and reduced regulatory molecules necessary for normal hematopoiesis. These data suggest that tissue stroma responds to malignant cells by disadvantaging normal parenchymal cells. Our taxonomy of the stromal compartment provides a comprehensive bone marrow cell census and experimental support for cancer cell crosstalk with specific stromal elements to impair normal tissue function and thereby enable emergent cancer., National Institutes of Health (Grant DK107784)

Published
2020

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