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2. Cell subtype-specific effects of genetic variation in the Alzheimer’s disease brain

Author

Fujita, Masashi, Gao, Zongmei, Zeng, Lu, McCabe, Cristin, White, Charles C., Ng, Bernard, Green, Gilad Sahar, Rozenblatt-Rosen, Orit, Phillips, Devan, Amir-Zilberstein, Liat, Lee, Hyo, Pearse, II, Richard V., Khan, Atlas, Vardarajan, Badri N., Kiryluk, Krzysztof, Ye, Chun Jimmie, Klein, Hans-Ulrich, Wang, Gao, Regev, Aviv, Habib, Naomi, Schneider, Julie A., Wang, Yanling, Young-Pearse, Tracy, Mostafavi, Sara, Bennett, David A., Menon, Vilas, and De Jager, Philip L.

Published
2024
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7. N-acetylneuraminic acid links immune exhaustion and accelerated memory deficit in diet-induced obese Alzheimer’s disease mouse model

Author

Suzzi, Stefano, Croese, Tommaso, Ravid, Adi, Gold, Or, Clark, Abbe R., Medina, Sedi, Kitsberg, Daniel, Adam, Miriam, Vernon, Katherine A., Kohnert, Eva, Shapira, Inbar, Malitsky, Sergey, Itkin, Maxim, Brandis, Alexander, Mehlman, Tevie, Salame, Tomer M., Colaiuta, Sarah P., Cahalon, Liora, Slyper, Michal, Greka, Anna, Habib, Naomi, and Schwartz, Michal

Published
2023
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9. Stroke genetics informs drug discovery and risk prediction across ancestries

Author

Mishra, Aniket, Malik, Rainer, Hachiya, Tsuyoshi, Jürgenson, Tuuli, Namba, Shinichi, Posner, Daniel C., Kamanu, Frederick K., Koido, Masaru, Le Grand, Quentin, Shi, Mingyang, He, Yunye, Georgakis, Marios K., Caro, Ilana, Krebs, Kristi, Liaw, Yi-Ching, Vaura, Felix C., Lin, Kuang, Winsvold, Bendik Slagsvold, Srinivasasainagendra, Vinodh, Parodi, Livia, Bae, Hee-Joon, Chauhan, Ganesh, Chong, Michael R., Tomppo, Liisa, Akinyemi, Rufus, Roshchupkin, Gennady V., Habib, Naomi, Jee, Yon Ho, Thomassen, Jesper Qvist, Abedi, Vida, Cárcel-Márquez, Jara, Nygaard, Marianne, Leonard, Hampton L., Yang, Chaojie, Yonova-Doing, Ekaterina, Knol, Maria J., Lewis, Adam J., Judy, Renae L., Ago, Tetsuro, Amouyel, Philippe, Armstrong, Nicole D., Bakker, Mark K., Bartz, Traci M., Bennett, David A., Bis, Joshua C., Bordes, Constance, Børte, Sigrid, Cain, Anael, Ridker, Paul M., Cho, Kelly, Chen, Zhengming, Cruchaga, Carlos, Cole, John W., de Jager, Phil L., de Cid, Rafael, Endres, Matthias, Ferreira, Leslie E., Geerlings, Mirjam I., Gasca, Natalie C., Gudnason, Vilmundur, Hata, Jun, He, Jing, Heath, Alicia K., Ho, Yuk-Lam, Havulinna, Aki S., Hopewell, Jemma C., Hyacinth, Hyacinth I., Inouye, Michael, Jacob, Mina A., Jeon, Christina E., Jern, Christina, Kamouchi, Masahiro, Keene, Keith L., Kitazono, Takanari, Kittner, Steven J., Konuma, Takahiro, Kumar, Amit, Lacaze, Paul, Launer, Lenore J., Lee, Keon-Joo, Lepik, Kaido, Li, Jiang, Li, Liming, Manichaikul, Ani, Markus, Hugh S., Marston, Nicholas A., Meitinger, Thomas, Mitchell, Braxton D., Montellano, Felipe A., Morisaki, Takayuki, Mosley, Thomas H., Nalls, Mike A., Nordestgaard, Børge G., O’Donnell, Martin J., Okada, Yukinori, Onland-Moret, N. Charlotte, Ovbiagele, Bruce, Peters, Annette, Psaty, Bruce M., Rich, Stephen S., Rosand, Jonathan, Sabatine, Marc S., Sacco, Ralph L., Saleheen, Danish, Sandset, Else Charlotte, Salomaa, Veikko, Sargurupremraj, Muralidharan, Sasaki, Makoto, Satizabal, Claudia L., Schmidt, Carsten O., Shimizu, Atsushi, Smith, Nicholas L., Sloane, Kelly L., Sutoh, Yoichi, Sun, Yan V., Tanno, Kozo, Tiedt, Steffen, Tatlisumak, Turgut, Torres-Aguila, Nuria P., Tiwari, Hemant K., Trégouët, David-Alexandre, Trompet, Stella, Tuladhar, Anil Man, Tybjærg-Hansen, Anne, van Vugt, Marion, Vibo, Riina, Verma, Shefali S., Wiggins, Kerri L., Wennberg, Patrik, Woo, Daniel, Wilson, Peter W. F., Xu, Huichun, Yang, Qiong, Yoon, Kyungheon, Millwood, Iona Y., Gieger, Christian, Ninomiya, Toshiharu, Grabe, Hans J., Jukema, J. Wouter, Rissanen, Ina L., Strbian, Daniel, Kim, Young Jin, Chen, Pei-Hsin, Mayerhofer, Ernst, Howson, Joanna M. M., Irvin, Marguerite R., Adams, Hieab, Wassertheil-Smoller, Sylvia, Christensen, Kaare, Ikram, Mohammad A., Rundek, Tatjana, Worrall, Bradford B., Lathrop, G. Mark, Riaz, Moeen, Simonsick, Eleanor M., Kõrv, Janika, França, Paulo H. C., Zand, Ramin, Prasad, Kameshwar, Frikke-Schmidt, Ruth, de Leeuw, Frank-Erik, Liman, Thomas, Haeusler, Karl Georg, Ruigrok, Ynte M., Heuschmann, Peter Ulrich, Longstreth, W. T., Jung, Keum Ji, Bastarache, Lisa, Paré, Guillaume, Damrauer, Scott M., Chasman, Daniel I., Rotter, Jerome I., Anderson, Christopher D., Zwart, John-Anker, Niiranen, Teemu J., Fornage, Myriam, Liaw, Yung-Po, Seshadri, Sudha, Fernández-Cadenas, Israel, Walters, Robin G., Ruff, Christian T., Owolabi, Mayowa O., Huffman, Jennifer E., Milani, Lili, Kamatani, Yoichiro, Dichgans, Martin, and Debette, Stephanie

Published
2022
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10. Massively parallel single-nucleus RNA-seq with DroNc-seq

Author

Habib, Naomi, Avraham-Davidi, Inbal, Basu, Anindita, Burks, Tyler, Shekhar, Karthik, Hofree, Matan, Choudhury, Sourav R, Aguet, François, Gelfand, Ellen, Ardlie, Kristin, Weitz, David A, Rozenblatt-Rosen, Orit, Zhang, Feng, and Regev, Aviv

Subjects
3T3 Cells, Animals, Biomarkers, HEK293 Cells, Humans, Mice, Principal Component Analysis, RNA, Sequence Analysis, RNA, Single-Cell Analysis, Transcription, Genetic, Biological Sciences, Technology, Medical and Health Sciences, Developmental Biology
Abstract

Single-nucleus RNA sequencing (sNuc-seq) profiles RNA from tissues that are preserved or cannot be dissociated, but it does not provide high throughput. Here, we develop DroNc-seq: massively parallel sNuc-seq with droplet technology. We profile 39,111 nuclei from mouse and human archived brain samples to demonstrate sensitive, efficient, and unbiased classification of cell types, paving the way for systematic charting of cell atlases.

Published
2017

11. Publisher Correction: Stroke genetics informs drug discovery and risk prediction across ancestries

Author

Mishra, Aniket, Malik, Rainer, Hachiya, Tsuyoshi, Jürgenson, Tuuli, Namba, Shinichi, Posner, Daniel C., Kamanu, Frederick K., Koido, Masaru, Le Grand, Quentin, Shi, Mingyang, He, Yunye, Georgakis, Marios K., Caro, Ilana, Krebs, Kristi, Liaw, Yi-Ching, Vaura, Felix C., Lin, Kuang, Winsvold, Bendik Slagsvold, Srinivasasainagendra, Vinodh, Parodi, Livia, Bae, Hee-Joon, Chauhan, Ganesh, Chong, Michael R., Tomppo, Liisa, Akinyemi, Rufus, Roshchupkin, Gennady V., Habib, Naomi, Jee, Yon Ho, Thomassen, Jesper Qvist, Abedi, Vida, Cárcel-Márquez, Jara, Nygaard, Marianne, Leonard, Hampton L., Yang, Chaojie, Yonova-Doing, Ekaterina, Knol, Maria J., Lewis, Adam J., Judy, Renae L., Ago, Tetsuro, Amouyel, Philippe, Armstrong, Nicole D., Bakker, Mark K., Bartz, Traci M., Bennett, David A., Bis, Joshua C., Bordes, Constance, Børte, Sigrid, Cain, Anael, Ridker, Paul M., Cho, Kelly, Chen, Zhengming, Cruchaga, Carlos, Cole, John W., de Jager, Phil L., de Cid, Rafael, Endres, Matthias, Ferreira, Leslie E., Geerlings, Mirjam I., Gasca, Natalie C., Gudnason, Vilmundur, Hata, Jun, He, Jing, Heath, Alicia K., Ho, Yuk-Lam, Havulinna, Aki S., Hopewell, Jemma C., Hyacinth, Hyacinth I., Inouye, Michael, Jacob, Mina A., Jeon, Christina E., Jern, Christina, Kamouchi, Masahiro, Keene, Keith L., Kitazono, Takanari, Kittner, Steven J., Konuma, Takahiro, Kumar, Amit, Lacaze, Paul, Launer, Lenore J., Lee, Keon-Joo, Lepik, Kaido, Li, Jiang, Li, Liming, Manichaikul, Ani, Markus, Hugh S., Marston, Nicholas A., Meitinger, Thomas, Mitchell, Braxton D., Montellano, Felipe A., Morisaki, Takayuki, Mosley, Thomas H., Nalls, Mike A., Nordestgaard, Børge G., O’Donnell, Martin J., Okada, Yukinori, Onland-Moret, N. Charlotte, Ovbiagele, Bruce, Peters, Annette, Psaty, Bruce M., Rich, Stephen S., Rosand, Jonathan, Sabatine, Marc S., Sacco, Ralph L., Saleheen, Danish, Sandset, Else Charlotte, Salomaa, Veikko, Sargurupremraj, Muralidharan, Sasaki, Makoto, Satizabal, Claudia L., Schmidt, Carsten O., Shimizu, Atsushi, Smith, Nicholas L., Sloane, Kelly L., Sutoh, Yoichi, Sun, Yan V., Tanno, Kozo, Tiedt, Steffen, Tatlisumak, Turgut, Torres-Aguila, Nuria P., Tiwari, Hemant K., Trégouët, David-Alexandre, Trompet, Stella, Tuladhar, Anil Man, Tybjærg-Hansen, Anne, van Vugt, Marion, Vibo, Riina, Verma, Shefali S., Wiggins, Kerri L., Wennberg, Patrik, Woo, Daniel, Wilson, Peter W. F., Xu, Huichun, Yang, Qiong, Yoon, Kyungheon, Millwood, Iona Y., Gieger, Christian, Ninomiya, Toshiharu, Grabe, Hans J., Jukema, J. Wouter, Rissanen, Ina L., Strbian, Daniel, Kim, Young Jin, Chen, Pei-Hsin, Mayerhofer, Ernst, Howson, Joanna M. M., Irvin, Marguerite R., Adams, Hieab, Wassertheil-Smoller, Sylvia, Christensen, Kaare, Ikram, Mohammad A., Rundek, Tatjana, Worrall, Bradford B., Lathrop, G. Mark, Riaz, Moeen, Simonsick, Eleanor M., Kõrv, Janika, França, Paulo H. C., Zand, Ramin, Prasad, Kameshwar, Frikke-Schmidt, Ruth, de Leeuw, Frank-Erik, Liman, Thomas, Haeusler, Karl Georg, Ruigrok, Ynte M., Heuschmann, Peter Ulrich, Longstreth, W. T., Jung, Keum Ji, Bastarache, Lisa, Paré, Guillaume, Damrauer, Scott M., Chasman, Daniel I., Rotter, Jerome I., Anderson, Christopher D., Zwart, John-Anker, Niiranen, Teemu J., Fornage, Myriam, Liaw, Yung-Po, Seshadri, Sudha, Fernández-Cadenas, Israel, Walters, Robin G., Ruff, Christian T., Owolabi, Mayowa O., Huffman, Jennifer E., Milani, Lili, Kamatani, Yoichiro, Dichgans, Martin, and Debette, Stephanie

Published
2022
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15. Molecular Connectomics Reveals a Glucagon-Like Peptide 1 Sensitive Neural Circuit for Satiety

Author

Webster, Addison N., primary, Becker, Jordan J., additional, Li, Chia, additional, Schwalbe, Dana C., additional, Kerspern, Damien, additional, Karolczak, Eva O., additional, Godschall, Elizabeth N., additional, Belmont-Rausch, Dylan Matthew, additional, Pers, Tune H., additional, Lutas, Andrew, additional, Habib, Naomi, additional, Güler, Ali D., additional, Krashes, Michael J., additional, and Campbell, John N., additional

Published
2023
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18. Genome-scale transcriptional activation by an engineered CRISPR-Cas9 complex

Author

Konermann, Silvana, Brigham, Mark D, Trevino, Alexandro E, Joung, Julia, Abudayyeh, Omar O, Barcena, Clea, Hsu, Patrick D, Habib, Naomi, Gootenberg, Jonathan S, Nishimasu, Hiroshi, Nureki, Osamu, and Zhang, Feng

Subjects
Genetics, Biotechnology, Human Genome, Cancer, Development of treatments and therapeutic interventions, 5.1 Pharmaceuticals, CRISPR-Associated Proteins, CRISPR-Cas Systems, Cell Line, Tumor, Clustered Regularly Interspaced Short Palindromic Repeats, DNA, Complementary, Drug Resistance, Neoplasm, Gene Expression Regulation, Neoplastic, Gene Library, Genetic Engineering, Genetic Loci, Genetic Testing, Genome, Human, Humans, Indoles, Melanoma, Proto-Oncogene Proteins B-raf, RNA, Untranslated, Reproducibility of Results, Sulfonamides, Transcriptional Activation, Up-Regulation, General Science & Technology
Abstract

Systematic interrogation of gene function requires the ability to perturb gene expression in a robust and generalizable manner. Here we describe structure-guided engineering of a CRISPR-Cas9 complex to mediate efficient transcriptional activation at endogenous genomic loci. We used these engineered Cas9 activation complexes to investigate single-guide RNA (sgRNA) targeting rules for effective transcriptional activation, to demonstrate multiplexed activation of ten genes simultaneously, and to upregulate long intergenic non-coding RNA (lincRNA) transcripts. We also synthesized a library consisting of 70,290 guides targeting all human RefSeq coding isoforms to screen for genes that, upon activation, confer resistance to a BRAF inhibitor. The top hits included genes previously shown to be able to confer resistance, and novel candidates were validated using individual sgRNA and complementary DNA overexpression. A gene expression signature based on the top screening hits correlated with markers of BRAF inhibitor resistance in cell lines and patient-derived samples. These results collectively demonstrate the potential of Cas9-based activators as a powerful genetic perturbation technology.

Published
2015

19. Human subcutaneous and visceral adipocyte atlases uncover classical and specialized adipocytes and depot-specific patterns

Author

Lazarescu, Or, primary, Ziv Agam, Maya, additional, Haim, Yulia, additional, Hekselman, Idan, additional, Jubran, Juman, additional, Shneyour, Ariel, additional, Kitsberg, Danny, additional, Levin, Liron, additional, Liberty, Idit F, additional, Yoel, Uri, additional, Dukhno, Oleg, additional, Adam, Miriam, additional, Korner, Antje, additional, Murphy, Rinki, additional, Bluher, Matthias, additional, Habib, Naomi, additional, Rudich, Assaf, additional, and Yeger-Lotem, Esti, additional

Published
2023
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20. Single cell RNA sequencing of human microglia uncovers a subset associated with Alzheimer’s disease

Author

Olah, Marta, Menon, Vilas, Habib, Naomi, Taga, Mariko F., Ma, Yiyi, Yung, Christina J., Cimpean, Maria, Khairallah, Anthony, Coronas-Samano, Guillermo, Sankowski, Roman, Grün, Dominic, Kroshilina, Alexandra A., Dionne, Danielle, Sarkis, Rani A., Cosgrove, Garth R., Helgager, Jeffrey, Golden, Jeffrey A., Pennell, Page B., Prinz, Marco, Vonsattel, Jean Paul G., Teich, Andrew F., Schneider, Julie A., Bennett, David A., Regev, Aviv, Elyaman, Wassim, Bradshaw, Elizabeth M., and De Jager, Philip L.

Published
2020
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22. Molecular Connectomics Reveals a Glucagon-Like Peptide 1 Sensitive Neural Circuit for Satiety

Author

Webster, Addison N, Becker, Jordan J, Li, Chia, Schwalbe, Dana C, Kerspern, Damien, Karolczak, Eva O, Godschall, Elizabeth N, Belmont-Rausch, Dylan Matthew, Pers, Tune H, Lutas, Andrew, Habib, Naomi, Güler, Ali D, Krashes, Michael J, Campbell, John N, Webster, Addison N, Becker, Jordan J, Li, Chia, Schwalbe, Dana C, Kerspern, Damien, Karolczak, Eva O, Godschall, Elizabeth N, Belmont-Rausch, Dylan Matthew, Pers, Tune H, Lutas, Andrew, Habib, Naomi, Güler, Ali D, Krashes, Michael J, and Campbell, John N

Abstract

Liraglutide and other agonists of the glucagon-like peptide 1 receptor (GLP-1RAs) are effective weight loss drugs, but how they suppress appetite remains unclear. GLP-1RAs inhibit hunger-promoting Agouti-related peptide (AgRP) neurons of the arcuate hypothalamus (Arc) but only indirectly, implicating synaptic afferents to AgRP neurons. To investigate, we developed a method combining rabies-based connectomics with single-nuclei transcriptomics. Applying this method to AgRP neurons in mice predicts 21 afferent subtypes in the mediobasal and paraventricular hypothalamus. Among these are Trh+ Arc neurons (TrhArc), which express the Glp1r gene and are activated by the GLP-1RA liraglutide. Activating TrhArc neurons inhibits AgRP neurons and decreases feeding in an AgRP neuron-dependent manner. Silencing TrhArc neurons increases feeding and body weight and reduces liraglutide’s satiating effects. Our results thus demonstrate a widely applicable method for molecular connectomics, reveal the molecular organization of AgRP neuron afferents, and shed light on a neurocircuit through which GLP-1RAs suppress appetite., Liraglutide and other agonists of the glucagon-like peptide 1 receptor (GLP-1RAs) are effective weight loss drugs, but how they suppress appetite remains unclear. GLP-1RAs inhibit hunger-promoting Agouti-related peptide (AgRP) neurons of the arcuate hypothalamus (Arc) but only indirectly, implicating synaptic afferents to AgRP neurons. To investigate, we developed a method combining rabies-based connectomics with single-nuclei transcriptomics. Applying this method to AgRP neurons in mice predicts 21 afferent subtypes in the mediobasal and paraventricular hypothalamus. Among these are Trh+ Arc neurons (TrhArc), which express the Glp1r gene and are activated by the GLP-1RA liraglutide. Activating TrhArc neurons inhibits AgRP neurons and decreases feeding in an AgRP neuron-dependent manner. Silencing TrhArc neurons increases feeding and body weight and reduces liraglutide's satiating effects. Our results thus demonstrate a widely applicable method for molecular connectomics, reveal the molecular organization of AgRP neuron afferents, and shed light on a neurocircuit through which GLP-1RAs suppress appetite.

Published
2023

27. Cellular network perturbations point to a new microglia‐astrocyte community accelerating Alzheimer’s disease progression

Author

Green, Gilad Sahar, primary, Fujita, Masashi, additional, Yang, Hyun‐Sik, additional, McCabe, Cristin, additional, Taga, Mariko, additional, Cain, Anael, additional, Zeng, Lu, additional, Regev, Aviv, additional, Bennett, David A, additional, Menon, Vilas, additional, Habib, Naomi, additional, and De Jager, Philip L, additional

Published
2022
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28. High‐throughput morphometric and transcriptomic profiling uncovers composition of naïve and sensory‐deprived cortical cholinergic VIP/CHAT neurons

Author

Yayon, Nadav, primary, Amsalem, Oren, additional, Zorbaz, Tamara, additional, Yakov, Or, additional, Dubnov, Serafima, additional, Winek, Katarzyna, additional, Dudai, Amir, additional, Adam, Gil, additional, Schmidtner, Anna K, additional, Tessier‐Lavigne, Marc, additional, Renier, Nicolas, additional, Habib, Naomi, additional, Segev, Idan, additional, London, Michael, additional, and Soreq, Hermona, additional

Published
2022
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29. Cell-subtype specific effects of genetic variation in the aging and Alzheimer cortex

Author

Fujita, Masashi, primary, Gao, Zongmei, additional, Zeng, Lu, additional, McCabe, Cristin, additional, White, Charles C., additional, Ng, Bernard, additional, Green, Gilad Sahar, additional, Rozenblatt-Rosen, Orit, additional, Phillips, Devan, additional, Amir-Zilberstein, Liat, additional, Lee, Hyo, additional, Pearse, Richard V., additional, Khan, Atlas, additional, Vardarajan, Badri N., additional, Kiryluk, Krzysztof, additional, Ye, Chun Jimmie, additional, Klein, Hans-Ulrich, additional, Wang, Gao, additional, Regev, Aviv, additional, Habib, Naomi, additional, Schneider, Julie A., additional, Wang, Yanling, additional, Young-Pearse, Tracy, additional, Mostafavi, Sara, additional, Bennett, David A., additional, Menon, Vilas, additional, and De Jager, Philip L., additional

Published
2022
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32. A cross-disease human microglial framework identifies disease-enriched subsets and tool compounds for microglial polarization

Author

Tuddenham, John F., primary, Taga, Mariko, additional, Haage, Verena, additional, Roostaei, Tina, additional, White, Charles, additional, Lee, Annie, additional, Fujita, Masashi, additional, Khairallah, Anthony, additional, Green, Gilad, additional, Hyman, Bradley, additional, Frosch, Matthew, additional, Hopp, Sarah, additional, Beach, Thomas G., additional, Corboy, John, additional, Habib, Naomi, additional, Klein, Hans-Ulrich, additional, Soni, Rajesh Kumar, additional, Teich, Andrew F., additional, Hickman, Richard A., additional, Alcalay, Roy N., additional, Shneider, Neil, additional, Schneider, Julie, additional, Sims, Peter A., additional, Bennett, David A., additional, Olah, Marta, additional, Menon, Vilas, additional, and De Jager, Philip L., additional

Published
2022
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35. High‐throughput morphometric and transcriptomic profiling uncovers composition of naïve and sensory‐deprived cortical cholinergic VIP/CHAT neurons.

Author

Yayon, Nadav, Amsalem, Oren, Zorbaz, Tamara, Yakov, Or, Dubnov, Serafima, Winek, Katarzyna, Dudai, Amir, Adam, Gil, Schmidtner, Anna K, Tessier‐Lavigne, Marc, Renier, Nicolas, Habib, Naomi, Segev, Idan, London, Michael, and Soreq, Hermona

Subjects
INTERNEURONS, NEURAL circuitry, TRANSCRIPTOMES, NEURONS, INNERVATION, THREE-dimensional imaging
Abstract

Cortical neuronal networks control cognitive output, but their composition and modulation remain elusive. Here, we studied the morphological and transcriptional diversity of cortical cholinergic VIP/ChAT interneurons (VChIs), a sparse population with a largely unknown function. We focused on VChIs from the whole barrel cortex and developed a high‐throughput automated reconstruction framework, termed PopRec, to characterize hundreds of VChIs from each mouse in an unbiased manner, while preserving 3D cortical coordinates in multiple cleared mouse brains, accumulating thousands of cells. We identified two fundamentally distinct morphological types of VChIs, bipolar and multipolar that differ in their cortical distribution and general morphological features. Following mild unilateral whisker deprivation on postnatal day seven, we found after three weeks both ipsi‐ and contralateral dendritic arborization differences and modified cortical depth and distribution patterns in the barrel fields alone. To seek the transcriptomic drivers, we developed NuNeX, a method for isolating nuclei from fixed tissues, to explore sorted VChIs. This highlighted differentially expressed neuronal structural transcripts, altered exitatory innervation pathways and established Elmo1 as a key regulator of morphology following deprivation. Synopsis: A novel pipeline enables integrated analysis of neuronal morphology, spatial distribution, and transcriptomic profile with a particular focus on cholinergic VIP/ChAT interneurons in the mouse barrel cortex. 3D morphometric profiling and reconstruction following 3D image normalization show two structurally distinct populations of bipolar and multipolar VChIs.Juvenile whisker‐deprived mice show alterations three weeks postsensory‐deprived deprivation in both barrel and global morphometric dendritic and cortical distributions of VChIs.Global transcriptome analysis of isolated VChIs from formalin‐fixed tissues highlights altered glutamatergic pathway and differential expression of Elmo1, Arpp21, and Sema5b in whisker‐deprived adult mice.Knockdown of ELMO1 perturbed dendrite morphology in human neuroblastoma and primary cultures of murine cortical neurons. [ABSTRACT FROM AUTHOR]

Published
2023
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37. Accelerated cognitive decline in obese mouse model of Alzheimer’s disease is linked to sialic acid-driven immune deregulation

Author

Suzzi, Stefano, primary, Croese, Tommaso, additional, Ravid, Adi, additional, Gold, Or, additional, Clark, Abbe R., additional, Medina, Sedi, additional, Kitsberg, Daniel, additional, Adam, Miriam, additional, Vernon, Katherine A., additional, Kohnert, Eva, additional, Shapira, Inbar, additional, Malitsky, Sergey, additional, Itkin, Maxim, additional, Colaiuta, Sarah P., additional, Cahalon, Liora, additional, Slyper, Michal, additional, Greka, Anna, additional, Habib, Naomi, additional, and Schwartz, Michal, additional

Published
2022
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38. Stroke genetics informs drug discovery and risk prediction across ancestries

Author

Debette, Stéphanie, primary, Mishra, Aniket, additional, Malik, Rainer, additional, Hachiya, Tsuyoshi, additional, Jürgenson, Tuuli, additional, Namba, Shinichi, additional, Koido, Masaru, additional, Grand, Quentin Le, additional, Kamanu, Frederick, additional, Shi, Mingyang, additional, He, Yunye, additional, Georgakis, Marios, additional, Caro, Ilana, additional, Krebs, Kristi, additional, Vaura, Felix, additional, Habib, Naomi, additional, Winsvold, Bendik, additional, Jee, Yon Ho, additional, Thomassen, Jesper Qvist, additional, Abedi, Vida, additional, Cárcel-Márquez, Jara, additional, Lin, Kuang, additional, Nygaard, Marianne, additional, Chauhan, Ganesh, additional, Leonard, Hampton, additional, Yang, Chaojie, additional, Yonova-Doing, Ekaterina, additional, Knol, Maria, additional, Ago, Tetsuro, additional, Amouyel, Philippe, additional, Anderson, Christopher, additional, Armstrong, Nicole, additional, Bakker, Mark, additional, Bartz, Traci, additional, Bis, Joshua, additional, Bordes, Constance, additional, Borte, Sigrid, additional, Cain, Anael, additional, Ridker, Paul, additional, Chen, Zhengming, additional, Chong, Michael, additional, Cole, John, additional, de Cid, Rafael, additional, Endres, Matthias, additional, Ferreira, Leslie, additional, Gasca, Natalie, additional, Gudnason, Vilmundur, additional, Hata, Jun, additional, Havulinna, Aki, additional, Hopewell, Jemma, additional, Hyacinth, Hyacinth, additional, Inouye, Michael, additional, Jacob, Mina, additional, Jeon, Christina , additional, Jern, Christina, additional, Kamouchi, Masahiro, additional, Keene, Keith, additional, Kitazono, Takanari, additional, Kittner, Steven, additional, Konuma, Takahiro, additional, Kumar, Amit, additional, Lacaze, Paul, additional, Launer, Lenore, additional, Lepik, Kaido, additional, Li, Jiang, additional, Li, Liming, additional, Manichaikul, Ani, additional, Markus, Hugh, additional, Marston, Nicholas, additional, Meitinger, Thomas, additional, Mitchell, Braxton, additional, Montellano, Felipe, additional, Morisaki, Takayuki, additional, Mosley, Thomas, additional, Nalls, Mike, additional, Nordestgaard, Børge, additional, O'Donnell, Martin, additional, Okada, Yukinori, additional, Pare, Guillaume, additional, Peters, Annette, additional, Psaty, Bruce, additional, Rich, Stephen, additional, Rosand, Jonathan, additional, Sabatine, Marc, additional, Sacco, Ralph, additional, Saleheen, Danish, additional, Sandset, Else Charlotte, additional, Sargurupremraj, Muralidharan, additional, Sasaki, Makoto, additional, Satizabal, Claudia, additional, Schmidt, Carsten, additional, Shimizu, Atsushi, additional, Smith, Nicholas, additional, Strbian, Daniel, additional, Sutoh, Yoichi, additional, Tanno, Kozo, additional, Tiedt, Steffen, additional, Torres-Aguila, Nuria, additional, Trégouët, David-Alexandre, additional, Trompet, Stella, additional, Tuladhar, Anil, additional, Tybjærg-Hansen, Anne, additional, Vugt, Marion van, additional, Vibo, Riina, additional, Wiggins, Kerri, additional, Woo, Daniel, additional, Xu, Huichun, additional, Yang, Qiong, additional, Lathrop, Mark, additional, Millwood, Iona, additional, Gieger, Christian, additional, Ninomiya, Toshiharu, additional, Grabe, Hans, additional, Jukema, J Wouter, additional, Rissanen, Ina, additional, Seshadri, Sudha, additional, Longstreth, William, additional, Chasman, Daniel, additional, Howson, Joanna, additional, Irvin, Marguerite, additional, Adams, Hieab, additional, Wasssertheil-Smoller, Sylvia, additional, Christensen, Kaare, additional, Ikram, M. Arfan, additional, Rundek, Tatjana, additional, Rotter, Jerome, additional, Riaz, Moeen, additional, Simonsick, Eleanor, additional, Kõrv, Janika, additional, França, Paulo, additional, Fornage, Myriam, additional, Zand, Ramin, additional, Prasad, Kameshwar, additional, Frikke-Schmidt, Ruth, additional, de Leeuw, Frank-Erik, additional, Liman, Thomas, additional, Haeusler, Karl Georg, additional, Ruigrok, Ynte, additional, Heuschmann, Peter, additional, Jung, Keum, additional, Zwart, John-Anker, additional, Niiranen, Teemu, additional, Ruff, Christian, additional, Fernández-Cadenas, Israel, additional, Walters, Robin, additional, Milani, Lili, additional, Kamatani, Yoichiro, additional, and Dichgans, Martin, additional

Published
2022
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39. Comparative Functional Genomics of the Fission Yeasts

Author

Rhind, Nicholas, Chen, Zehua, Yassour, Moran, Thompson, Dawn A., Haas, Brian J., Habib, Naomi, Wapinski, Ilan, Roy, Sushmita, Lin, Michael F., Heiman, David I., Young, Sarah K., Furuya, Kanji, Guo, Yabin, Pidoux, Alison, Chen, Huei Mei, Robbertse, Barbara, Goldberg, Jonathan M., Aoki, Keita, Bayne, Elizabeth H., Berlin, Aaron M., Desjardins, Christopher A., Dobbs, Edward, Dukaj, Livio, Fan, Lin, FitzGerald, Michael G., French, Courtney, Gujja, Sharvari, Hansen, Klavs, Keifenheim, Dan, Levin, Joshua Z., Mosher, Rebecca A., Müller, Carolin A., Pfiffner, Jenna, Priest, Margaret, Russ, Carsten, Smialowska, Agata, Swoboda, Peter, Sykes, Sean M., Vaughn, Matthew, Vengrova, Sonya, Yoder, Ryan, Zeng, Qiandong, Allshire, Robin, Baulcombe, David, Birren, Bruce W., Brown, William, Ekwall, Karl, Kellis, Manolis, Leatherwood, Janet, Levin, Henry, Margalit, Hanah, Martienssen, Rob, Nieduszynski, Conrad A., Spatafora, Joseph W., Friedman, Nir, Dalgaard, Jacob Z., Baumann, Peter, Niki, Hironori, Regev, Aviv, and Nusbaum, Chad

Published
2011
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40. Early sample tagging and pooling enables simultaneous SARS-CoV-2 detection and variant sequencing

Author

Chappleboim, Alon, primary, Joseph-Strauss, Daphna, additional, Rahat, Ayelet, additional, Sharkia, Israa, additional, Adam, Miriam, additional, Kitsberg, Daniel, additional, Fialkoff, Gavriel, additional, Lotem, Matan, additional, Gershon, Omer, additional, Schmidtner, Anna-Kristina, additional, Oiknine-Djian, Esther, additional, Klochendler, Agnes, additional, Sadeh, Ronen, additional, Dor, Yuval, additional, Wolf, Dana, additional, Habib, Naomi, additional, and Friedman, Nir, additional

Published
2021
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41. Single cell biology—a Keystone Symposia report

Author

Cable, Jennifer, primary, Elowitz, Michael B., additional, Domingos, Ana I., additional, Habib, Naomi, additional, Itzkovitz, Shalev, additional, Hamidzada, Homaira, additional, Balzer, Michael S., additional, Yanai, Itai, additional, Liberali, Prisca, additional, Whited, Jessica, additional, Streets, Aaron, additional, Cai, Long, additional, Stergachis, Andrew B., additional, Hong, Clarice Kit Yee, additional, Keren, Leeat, additional, Guilliams, Martin, additional, Alon, Uri, additional, Shalek, Alex K., additional, Hamel, Regan, additional, Pfau, Sarah J., additional, Raj, Arjun, additional, Quake, Stephen R., additional, Zhang, Nancy R., additional, Fan, Jean, additional, Trapnell, Cole, additional, Wang, Bo, additional, Greenwald, Noah F., additional, Vento‐Tormo, Roser, additional, Santos, Silvia D.M., additional, Spencer, Sabrina L., additional, Garcia, Hernan G., additional, Arekatla, Geethika, additional, Gaiti, Federico, additional, Arbel‐Goren, Rinat, additional, Rulands, Steffen, additional, Junker, Jan Philipp, additional, Klein, Allon M., additional, Morris, Samantha A., additional, Murray, John I., additional, Galloway, Kate E., additional, Ratz, Michael, additional, and Romeike, Merrit, additional

Published
2021
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45. Single cell biology—a Keystone Symposia report

Author

Cable, Jennifer, Elowitz, Michael B., Domingos, Ana I., Habib, Naomi, Itzkovitz, Shalev, Hamidzada, Homaira, Balzer, Michael S., Yanai, Itai, Liberali, Prisca, Whited, Jessica, Streets, Aaron, Cai, Long, Stergachis, Andrew B., Hong, Clarice Kit Yee, Keren, Leeat, Guilliams, Martin, Alon, Uri, Shalek, Alex K., Hamel, Regan, Pfau, Sarah J., Raj, Arjun, Quake, Stephen R., Zhang, Nancy R., Fan, Jean, Trapnell, Cole, Wang, Bo, Greenwald, Noah F., Vento‐Tormo, Roser, Santos, Silvia D. M., Spencer, Sabrina L., Garcia, Hernan G., Arekatla, Geethika, Gaiti, Federico, Arbel‐Goren, Rinat, Rulands, Steffen, Junker, Jan Philipp, Klein, Allon M., Morris, Samantha A., Murray, John I., Galloway, Kate E., Ratz, Michael, Romeike, Merrit, Cable, Jennifer, Elowitz, Michael B., Domingos, Ana I., Habib, Naomi, Itzkovitz, Shalev, Hamidzada, Homaira, Balzer, Michael S., Yanai, Itai, Liberali, Prisca, Whited, Jessica, Streets, Aaron, Cai, Long, Stergachis, Andrew B., Hong, Clarice Kit Yee, Keren, Leeat, Guilliams, Martin, Alon, Uri, Shalek, Alex K., Hamel, Regan, Pfau, Sarah J., Raj, Arjun, Quake, Stephen R., Zhang, Nancy R., Fan, Jean, Trapnell, Cole, Wang, Bo, Greenwald, Noah F., Vento‐Tormo, Roser, Santos, Silvia D. M., Spencer, Sabrina L., Garcia, Hernan G., Arekatla, Geethika, Gaiti, Federico, Arbel‐Goren, Rinat, Rulands, Steffen, Junker, Jan Philipp, Klein, Allon M., Morris, Samantha A., Murray, John I., Galloway, Kate E., Ratz, Michael, and Romeike, Merrit

Abstract

Single cell biology has the potential to elucidate many critical biological processes and diseases, from development and regeneration to cancer. Single cell analyses are uncovering the molecular diversity of cells, revealing a clearer picture of the variation among and between different cell types. New techniques are beginning to unravel how differences in cell state—transcriptional, epigenetic, and other characteristics—can lead to different cell fates among genetically identical cells, which underlies complex processes such as embryonic development, drug resistance, response to injury, and cellular reprogramming. Single cell technologies also pose significant challenges relating to processing and analyzing vast amounts of data collected. To realize the potential of single cell technologies, new computational approaches are needed. On March 17–19, 2021, experts in single cell biology met virtually for the Keystone eSymposium “Single Cell Biology” to discuss advances both in single cell applications and technologies.

Published
2021

46. Single cell RNA sequencing of human microglia uncovers a subset associated with Alzheimer’s disease

Author

Massachusetts Institute of Technology. Department of Biology, Howard Hughes Medical Institute, Olah, Marta, Menon, Vilas, Habib, Naomi, Taga, Mariko F, Ma, Yiyi, Yung, Christina J, Cimpean, Maria, Khairallah, Anthony, Coronas-Samano, Guillermo, Sankowski, Roman, Grün, Dominic, Kroshilina, Alexandra A, Dionne, Danielle, Sarkis, Rani A, Cosgrove, Garth R, Helgager, Jeffrey, Golden, Jeffrey A, Pennell, Page B, Prinz, Marco, Vonsattel, Jean Paul G, Teich, Andrew F, Schneider, Julie A, Bennett, David A, Regev, Aviv, Elyaman, Wassim, Bradshaw, Elizabeth M, De Jager, Philip L, Massachusetts Institute of Technology. Department of Biology, Howard Hughes Medical Institute, Olah, Marta, Menon, Vilas, Habib, Naomi, Taga, Mariko F, Ma, Yiyi, Yung, Christina J, Cimpean, Maria, Khairallah, Anthony, Coronas-Samano, Guillermo, Sankowski, Roman, Grün, Dominic, Kroshilina, Alexandra A, Dionne, Danielle, Sarkis, Rani A, Cosgrove, Garth R, Helgager, Jeffrey, Golden, Jeffrey A, Pennell, Page B, Prinz, Marco, Vonsattel, Jean Paul G, Teich, Andrew F, Schneider, Julie A, Bennett, David A, Regev, Aviv, Elyaman, Wassim, Bradshaw, Elizabeth M, and De Jager, Philip L

Abstract

© 2020, The Author(s). The extent of microglial heterogeneity in humans remains a central yet poorly explored question in light of the development of therapies targeting this cell type. Here, we investigate the population structure of live microglia purified from human cerebral cortex samples obtained at autopsy and during neurosurgical procedures. Using single cell RNA sequencing, we find that some subsets are enriched for disease-related genes and RNA signatures. We confirm the presence of four of these microglial subpopulations histologically and illustrate the utility of our data by characterizing further microglial cluster 7, enriched for genes depleted in the cortex of individuals with Alzheimer’s disease (AD). Histologically, these cluster 7 microglia are reduced in frequency in AD tissue, and we validate this observation in an independent set of single nucleus data. Thus, our live human microglia identify a range of subtypes, and we prioritize one of these as being altered in AD.

Published
2021

47. A cellular and spatial map of the choroid plexus across brain ventricles and ages

Author

Dani, Neil, primary, Herbst, Rebecca H., additional, McCabe, Cristin, additional, Green, Gilad S., additional, Kaiser, Karol, additional, Head, Joshua P., additional, Cui, Jin, additional, Shipley, Frederick B., additional, Jang, Ahram, additional, Dionne, Danielle, additional, Nguyen, Lan, additional, Rodman, Christopher, additional, Riesenfeld, Samantha J., additional, Prochazka, Jan, additional, Prochazkova, Michaela, additional, Sedlacek, Radislav, additional, Zhang, Feng, additional, Bryja, Vitezslav, additional, Rozenblatt-Rosen, Orit, additional, Habib, Naomi, additional, Regev, Aviv, additional, and Lehtinen, Maria K., additional

Published
2021
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48. Multi-cellular communities are perturbed in the aging human brain and Alzheimer’s disease

Author

Cain, Anael, primary, Taga, Mariko, additional, McCabe, Cristin, additional, Green, Gilad, additional, Hekselman, Idan, additional, White, Charles C., additional, Lee, Dylan I., additional, Gaur, Pallavi, additional, Rozenblatt-Rosen, Orit, additional, Zhang, Feng, additional, Yeger-Lotem, Esti, additional, Bennett, David A., additional, Yang, Hyun-Sik, additional, Regev, Aviv, additional, Menon, Vilas, additional, Habib, Naomi, additional, and De Jager, Philip L., additional

Published
2020
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49. Single cell RNA sequencing of human microglia uncovers a subset that is associated with Alzheimer’s disease

Author

Olah, Marta, primary, Menon, Vilas, additional, Habib, Naomi, additional, Taga, Mariko, additional, Ma, Yiyi, additional, Khairallah, Anthony, additional, Yung, Christina J., additional, Coronas‐Samano, Guillermo, additional, Vonsattel, Jean P, additional, Teich, Andrew F., additional, Schneider, Julie A., additional, Bennett, David A., additional, Regev, Aviv, additional, and De Jager, Philip L., additional

Published
2020
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50. ATS Core Curriculum 2020. Adult Pulmonary Medicine

Author

Channick, Colleen L., primary, Garrison, Garth, additional, Huie, Tristan J., additional, Narewski, Erin, additional, Caplan-Shaw, Caralee, additional, Cho, Josalyn, additional, Rafeq, Samaan, additional, Alalawi, Raed, additional, Alashram, Rami, additional, Bailey, Kristina L., additional, Carmona, Eva M., additional, Habib, Naomi, additional, Kapolka, Rebecca, additional, Krishnan, Amita, additional, Lammi, Matthew R., additional, Peck, Tyler, additional, Pennington, Kelly M., additional, Rali, Parth, additional, Small, Bronwyn L., additional, Swenson, Colin, additional, Witkin, Alison, additional, and Hayes, Margaret M., additional

Published
2020
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