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1. Astrocytic β-catenin signaling via TCF7L2 regulates synapse development and social behavior.

Author

Szewczyk, Lukasz, Lipiec, Marcin, Liszewska, Ewa, Meyza, Ksenia, Urban-Ciecko, Joanna, Kondrakiewicz, Ludwika, Goncerzewicz, Anna, Rafalko, Kamil, Krawczyk, Tomasz, Bogaj, Karolina, Vainchtein, Ilia, Nakao-Inoue, Hiromi, Puscian, Alicja, Knapska, Ewelina, Jan Nowakowski, Tomasz, Wisniewska, Marta, Molofsky, Anna Victoria, and Sanders, Stephan

Subjects
Animals, Astrocytes, beta Catenin, Mice, Social Behavior, Transcription Factor 7-Like 2 Protein, Wnt Signaling Pathway, Synapses, Humans, Mice, Knockout, Male, Mice, Inbred C57BL, Brain, Autism Spectrum Disorder, Female
Abstract

The Wnt/β-catenin pathway contains multiple high-confidence risk genes that are linked to neurodevelopmental disorders, including autism spectrum disorder. However, its ubiquitous roles across brain cell types and developmental stages have made it challenging to define its impact on neural circuit development and behavior. Here, we show that TCF7L2, which is a key transcriptional effector of the Wnt/β-catenin pathway, plays a cell-autonomous role in postnatal astrocyte maturation and impacts adult social behavior. TCF7L2 was the dominant Wnt effector that was expressed in both mouse and human astrocytes, with a peak during astrocyte maturation. The conditional knockout of Tcf7l2 in postnatal astrocytes led to an enlargement of astrocytes with defective tiling and gap junction coupling. These mice also exhibited an increase in the number of cortical excitatory and inhibitory synapses and a marked increase in social interaction by adulthood. These data reveal an astrocytic role for developmental Wnt/β-catenin signaling in restricting excitatory synapse numbers and regulating adult social behavior.

Published
2024

2. Defining microglial-synapse interactions

Author

Eyo, Ukpong and Molofsky, Anna Victoria

Subjects
Information and Computing Sciences, Biomedical and Clinical Sciences, Machine Learning, Animals, Humans, Mice, Brain, Immunity, Innate, Macrophages, Microglia, Neuronal Plasticity, Synapses, General Science & Technology
Abstract

The brain's resident macrophages have many roles beyond synaptic pruning.

Published
2023

3. Microglia states and nomenclature: A field at its crossroads

Author

Paolicelli, Rosa C, Sierra, Amanda, Stevens, Beth, Tremblay, Marie-Eve, Aguzzi, Adriano, Ajami, Bahareh, Amit, Ido, Audinat, Etienne, Bechmann, Ingo, Bennett, Mariko, Bennett, Frederick, Bessis, Alain, Biber, Knut, Bilbo, Staci, Blurton-Jones, Mathew, Boddeke, Erik, Brites, Dora, Brône, Bert, Brown, Guy C, Butovsky, Oleg, Carson, Monica J, Castellano, Bernardo, Colonna, Marco, Cowley, Sally A, Cunningham, Colm, Davalos, Dimitrios, De Jager, Philip L, de Strooper, Bart, Denes, Adam, Eggen, Bart JL, Eyo, Ukpong, Galea, Elena, Garel, Sonia, Ginhoux, Florent, Glass, Christopher K, Gokce, Ozgun, Gomez-Nicola, Diego, González, Berta, Gordon, Siamon, Graeber, Manuel B, Greenhalgh, Andrew D, Gressens, Pierre, Greter, Melanie, Gutmann, David H, Haass, Christian, Heneka, Michael T, Heppner, Frank L, Hong, Soyon, Hume, David A, Jung, Steffen, Kettenmann, Helmut, Kipnis, Jonathan, Koyama, Ryuta, Lemke, Greg, Lynch, Marina, Majewska, Ania, Malcangio, Marzia, Malm, Tarja, Mancuso, Renzo, Masuda, Takahiro, Matteoli, Michela, McColl, Barry W, Miron, Veronique E, Molofsky, Anna Victoria, Monje, Michelle, Mracsko, Eva, Nadjar, Agnes, Neher, Jonas J, Neniskyte, Urte, Neumann, Harald, Noda, Mami, Peng, Bo, Peri, Francesca, Perry, V Hugh, Popovich, Phillip G, Pridans, Clare, Priller, Josef, Prinz, Marco, Ragozzino, Davide, Ransohoff, Richard M, Salter, Michael W, Schaefer, Anne, Schafer, Dorothy P, Schwartz, Michal, Simons, Mikael, Smith, Cody J, Streit, Wolfgang J, Tay, Tuan Leng, Tsai, Li-Huei, Verkhratsky, Alexei, von Bernhardi, Rommy, Wake, Hiroaki, Wittamer, Valérie, Wolf, Susanne A, Wu, Long-Jun, and Wyss-Coray, Tony

Subjects
Microglia, Neurosciences, Psychology, Cognitive Sciences, Neurology & Neurosurgery
Abstract

Microglial research has advanced considerably in recent decades yet has been constrained by a rolling series of dichotomies such as "resting versus activated" and "M1 versus M2." This dualistic classification of good or bad microglia is inconsistent with the wide repertoire of microglial states and functions in development, plasticity, aging, and diseases that were elucidated in recent years. New designations continuously arising in an attempt to describe the different microglial states, notably defined using transcriptomics and proteomics, may easily lead to a misleading, although unintentional, coupling of categories and functions. To address these issues, we assembled a group of multidisciplinary experts to discuss our current understanding of microglial states as a dynamic concept and the importance of addressing microglial function. Here, we provide a conceptual framework and recommendations on the use of microglial nomenclature for researchers, reviewers, and editors, which will serve as the foundations for a future white paper.

Published
2022

4. Astrocyte-encoded positional cues maintain sensorimotor circuit integrity.

Author

Molofsky, Anna Victoria, Kelley, Kevin, Tsai, Hui-Hsin, Redmond, Stephanie, Chang, Sandra, Madireddy, Lohith, Chan, Jonah, Baranzini, Sergio, Ullian, Erik, and Rowitch, David

Subjects
Animals, Astrocytes, Axons, Cell Polarity, Cell Survival, Humans, Mice, Motor Neurons, Neural Pathways, Semaphorin-3A, Sensory Receptor Cells, Spinal Cord, Synapses
Abstract

Astrocytes, the most abundant cells in the central nervous system, promote synapse formation and help to refine neural connectivity. Although they are allocated to spatially distinct regional domains during development, it is unknown whether region-restricted astrocytes are functionally heterogeneous. Here we show that postnatal spinal cord astrocytes express several region-specific genes, and that ventral astrocyte-encoded semaphorin 3a (Sema3a) is required for proper motor neuron and sensory neuron circuit organization. Loss of astrocyte-encoded Sema3a leads to dysregulated α-motor neuron axon initial segment orientation, markedly abnormal synaptic inputs, and selective death of α- but not of adjacent γ-motor neurons. In addition, a subset of TrkA(+) sensory afferents projects to ectopic ventral positions. These findings demonstrate that stable maintenance of a positional cue by developing astrocytes influences multiple aspects of sensorimotor circuit formation. More generally, they suggest that regional astrocyte heterogeneity may help to coordinate postnatal neural circuit refinement.

Published
2014

5. Astrocytic β-catenin signaling via TCF7L2 regulates synapse development and social behavior

Author

Szewczyk, Lukasz Mateusz, primary, Lipiec, Marcin Andrzej, additional, Liszewska, Ewa, additional, Meyza, Ksenia, additional, Urban-Ciecko, Joanna, additional, Kondrakiewicz, Ludwika, additional, Goncerzewicz, Anna, additional, Rafalko, Kamil, additional, Krawczyk, Tomasz Grzegorz, additional, Bogaj, Karolina, additional, Vainchtein, Ilia Davidovich, additional, Nakao-Inoue, Hiromi, additional, Puscian, Alicja, additional, Knapska, Ewelina, additional, Sanders, Stephan J., additional, Jan Nowakowski, Tomasz, additional, Molofsky, Anna Victoria, additional, and Wisniewska, Marta Barbara, additional

Published
2023
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6. Contributors

Author

Akassoglou, Katerina, primary, Allen, Nicola J., additional, Alsina, Fernando C., additional, Alunni, Alessandro, additional, Alvarez-Buylla, A., additional, Andrews, Madeline G., additional, Ang, S.-L., additional, Appel, B., additional, Arefin, Badrul, additional, Bahrampour, Shahrzad, additional, Bai, Q.-R., additional, Bally-Cuif, Laure, additional, Batista-Brito, Renata, additional, Baumgardt, Magnus, additional, Benito-Sipos, Jonathan, additional, Bergles, D.E., additional, Bhaduri, Aparna, additional, Blaess, S., additional, Bonney, Stephanie, additional, Bosze, Bernadett, additional, Breunig, Joshua J., additional, Brown, Nadean L., additional, Buffington, S.A., additional, Call, C.L., additional, Campbell, K., additional, Cardona, Astrid E., additional, Catela, Catarina, additional, Cebrián-Silla, A., additional, Cheng, Yi-Ting, additional, Chizhikov, Victor V., additional, Coolen, Marion, additional, Curt, Jesús Rodriguez, additional, Davalos, Dimitrios, additional, De Biase, L.M., additional, Deneen, Benjamin, additional, Durak, Omer, additional, Fame, Ryann M., additional, Fancy, Stephen P.J., additional, Fishell, Gord, additional, Foucher, Isabelle, additional, Fuentealba, L., additional, Gage, Fred H., additional, Galas, Ludovic, additional, Grande, Andrew W., additional, Grove, Elizabeth A., additional, Haigh, J.L., additional, Hébert, Jean, additional, Hobert, Oliver, additional, Hufnagel, Robert B., additional, Huttner, Wieland B., additional, Itoh, Yasuhiro, additional, Jessen, K.R., additional, Johnson, Jane E., additional, Karzbrun, Eyal, additional, Komuro, Yutaro, additional, Komuro, Hitoshi, additional, Kriegstein, Arnold R., additional, Lambert, J.T., additional, Long, Katherine R., additional, López-Bendito, Guillermina, additional, MacDonald, Jessica L., additional, Macklis, Jeffrey D., additional, Marchetto, Maria Carolina, additional, Martini, Francisco J., additional, Matise, Michael P., additional, Merkle, F.T., additional, Meunier, A., additional, Millen, Kathleen J., additional, Miller, Robert H., additional, Mirsky, R., additional, Mishra, Swati, additional, Molofsky, Anna Victoria, additional, Monedero Cobeta, Ignacio, additional, Monk, K., additional, Monuki, Edwin S., additional, Nakafuku, Masato, additional, Nakamura, Harukazu, additional, Nelson, Branden R., additional, Nord, A.S., additional, Obernier, K., additional, Ohno, Nobuhiko, additional, Ozkan, Abdulkadir, additional, Parkinson, David B., additional, Peter, Manuel, additional, Pleasure, Samuel J., additional, Rasband, M.N., additional, Reiner, Orly, additional, Rowitch, D.H., additional, Rubenstein, J.L.R., additional, Sardar, Debosmita, additional, Sarkar, Anindita, additional, Sawamoto, K., additional, Sharma, Kamal, additional, Shen, Q., additional, Siegenthaler, Julie A., additional, Silver, Debra L., additional, Spassky, N., additional, Stott, S.R.W., additional, Stratmann, Johannes, additional, Subramanian, L., additional, Svaren, John, additional, Szewczyk, Lukasz Mateusz, additional, Temple, S., additional, Thor, Stefan, additional, Tole, Shubha, additional, Valdez, Gregorio, additional, Vaudry, David, additional, Ward, Claire, additional, Wegner, Michael, additional, and Yaghmaeian Salmani, Behzad, additional

Published
2020
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8. Expression profiling of Aldh1l1-precursors in the developing spinal cord reveals glial lineage-specific genes and direct Sox9-Nfe2l1 interactions.

Author

Glasgow, Stacey, Chaboub, Lesley, Tsai, Hui-Hsin, Murnen, Alice, Kelley, Kevin, Yuen, Tracy, Madireddy, Lohith, Deneen, Benjamin, Baranzini, Sergio, Fancy, Stephen, Rowitch, David, Molofsky, Anna Victoria, and Oldham, Michael

Subjects
Nfe2l1, astrocytes, expression profiling, gene coexpression, gliogenesis, Age Factors, Aldehyde Dehydrogenase 1 Family, Animals, Cell Differentiation, Cells, Cultured, Chickens, Computational Biology, Electroporation, Embryo, Mammalian, Flow Cytometry, Gene Expression Profiling, Gene Expression Regulation, Developmental, Glial Fibrillary Acidic Protein, Green Fluorescent Proteins, Isoenzymes, Mice, Mice, Transgenic, NF-E2-Related Factor 1, Nerve Tissue Proteins, Neuroglia, Neurons, Oligonucleotide Array Sequence Analysis, Retinal Dehydrogenase, SOX9 Transcription Factor, Spinal Cord, Transcription Factors
Abstract

Developmental regulation of gliogenesis in the mammalian CNS is incompletely understood, in part due to a limited repertoire of lineage-specific genes. We used Aldh1l1-GFP as a marker for gliogenic radial glia and later-stage precursors of developing astrocytes and performed gene expression profiling of these cells. We then used this dataset to identify candidate transcription factors that may serve as glial markers or regulators of glial fate. Our analysis generated a database of developmental stage-related markers of Aldh1l1+ cells between murine embryonic day 13.5-18.5. Using these data we identify the bZIP transcription factor Nfe2l1 and demonstrate that it promotes glial fate under direct Sox9 regulatory control. Thus, this dataset represents a resource for identifying novel regulators of glial development.

Published
2013

9. Microglia states and nomenclature: A field at its crossroads.

Author

Paolicelli, Rosa C., Sierra, Amanda, Stevens, Beth, Tremblay, Marie-Eve, Aguzzi, Adriano, Ajami, Bahareh, Amit, Ido, Audinat, Etienne, Bechmann, Ingo, Bennett, Mariko, Bennett, Frederick, Bessis, Alain, Biber, Knut, Bilbo, Staci, Blurton-Jones, Mathew, Boddeke, Erik, Brites, Dora, Brône, Bert, Brown, Guy C., Butovsky, Oleg, Carson, Monica J., Castellano, Bernardo, Colonna, Marco, Cowley, Sally A., Cunningham, Colm, Davalos, Dimitrios, De Jager, Philip L., de Strooper, Bart, Denes, Adam, Eggen, Bart J. L., Eyo, Ukpong, Galea, Elena, Garel, Sonia, Ginhoux, Florent, Glass, Christopher K., Gokce, Ozgun, Gomez-Nicola, Diego, González, Berta, Gordon, Siamon, Graeber, Manuel B., Greenhalgh, Andrew D., Gressens, Pierre, Greter, Melanie, Gutmann, David H., Haass, Christian, Heneka, Michael, Heppner, Frank L., Hong, Soyon, Hume, David A., Jung, Steffen, Kettenmann, Helmut, Kipnis, Jonathan, Koyama, Ryuta, Lemke, Greg, Lynch, Marina, Majewska, Ania, Malcangio, Marzia, Malm, Tarja, Mancuso, Renzo, Masuda, Takahiro, Matteoli, Michela, McColl, Barry W., Miron, Veronique E., Molofsky, Anna Victoria, Monje, Michelle, Mracsko, Eva, Nadjar, Agnes, Neher, Jonas J., Neniskyte, Urte, Neumann, Harald, Noda, Mami, Peng, Bo, Peri, Francesca, Perry, V. Hugh, Popovich, Phillip G., Pridans, Clare, Priller, Josef, Prinz, Marco, Ragozzino, Davide, Ransohoff, Richard M., Salter, Michael W., Schaefer, Anne, Schafer, Dorothy P., Schwartz, Michal, Simons, Mikael, Smith, Cody J., Streit, Wolfgang J., Tay, Tuan Leng, Tsai, Li-Huei, Verkhratsky, Alexei, von Bernhardi, Rommy, Wake, Hiroaki, Wittamer, Valérie, Wolf, Susanne A., Wu, Long-Jun, Wyss-Coray, Tony, Paolicelli, Rosa C., Sierra, Amanda, Stevens, Beth, Tremblay, Marie-Eve, Aguzzi, Adriano, Ajami, Bahareh, Amit, Ido, Audinat, Etienne, Bechmann, Ingo, Bennett, Mariko, Bennett, Frederick, Bessis, Alain, Biber, Knut, Bilbo, Staci, Blurton-Jones, Mathew, Boddeke, Erik, Brites, Dora, Brône, Bert, Brown, Guy C., Butovsky, Oleg, Carson, Monica J., Castellano, Bernardo, Colonna, Marco, Cowley, Sally A., Cunningham, Colm, Davalos, Dimitrios, De Jager, Philip L., de Strooper, Bart, Denes, Adam, Eggen, Bart J. L., Eyo, Ukpong, Galea, Elena, Garel, Sonia, Ginhoux, Florent, Glass, Christopher K., Gokce, Ozgun, Gomez-Nicola, Diego, González, Berta, Gordon, Siamon, Graeber, Manuel B., Greenhalgh, Andrew D., Gressens, Pierre, Greter, Melanie, Gutmann, David H., Haass, Christian, Heneka, Michael, Heppner, Frank L., Hong, Soyon, Hume, David A., Jung, Steffen, Kettenmann, Helmut, Kipnis, Jonathan, Koyama, Ryuta, Lemke, Greg, Lynch, Marina, Majewska, Ania, Malcangio, Marzia, Malm, Tarja, Mancuso, Renzo, Masuda, Takahiro, Matteoli, Michela, McColl, Barry W., Miron, Veronique E., Molofsky, Anna Victoria, Monje, Michelle, Mracsko, Eva, Nadjar, Agnes, Neher, Jonas J., Neniskyte, Urte, Neumann, Harald, Noda, Mami, Peng, Bo, Peri, Francesca, Perry, V. Hugh, Popovich, Phillip G., Pridans, Clare, Priller, Josef, Prinz, Marco, Ragozzino, Davide, Ransohoff, Richard M., Salter, Michael W., Schaefer, Anne, Schafer, Dorothy P., Schwartz, Michal, Simons, Mikael, Smith, Cody J., Streit, Wolfgang J., Tay, Tuan Leng, Tsai, Li-Huei, Verkhratsky, Alexei, von Bernhardi, Rommy, Wake, Hiroaki, Wittamer, Valérie, Wolf, Susanne A., Wu, Long-Jun, and Wyss-Coray, Tony

Abstract

Microglial research has advanced considerably in recent decades yet has been constrained by a rolling series of dichotomies such as "resting versus activated" and "M1 versus M2." This dualistic classification of good or bad microglia is inconsistent with the wide repertoire of microglial states and functions in development, plasticity, aging, and diseases that were elucidated in recent years. New designations continuously arising in an attempt to describe the different microglial states, notably defined using transcriptomics and proteomics, may easily lead to a misleading, although unintentional, coupling of categories and functions. To address these issues, we assembled a group of multidisciplinary experts to discuss our current understanding of microglial states as a dynamic concept and the importance of addressing microglial function. Here, we provide a conceptual framework and recommendations on the use of microglial nomenclature for researchers, reviewers, and editors, which will serve as the foundations for a future white paper.

Published
2022

10. Microglia states and nomenclature: A field at its crossroads.

Author

Paolicelli, Rosa RC, Sierra, Amanda, Stevens, Beth, Tremblay, Marie-Eve, Aguzzi, Adriano, Ajami, Bahareh, Amit, Ido, Audinat, Etienne, Bechmann, Ingo, Bennett, Mariko, Bennett, Frederick, Bessis, Alain, Biber, Knut, Bilbo, Staci, Blurton-Jones, Mathew, Boddeke, Erik, Brites, Dora, Brône, Bert, Brown, Guy C, Butovsky, Oleg, Carson, Monica J, Castellano, Bernardo, Colonna, Marco, Cowley, Sally A, Cunningham, Colm, Davalos, Dimitrios, De Jager, Philip L, De Strooper, Bart, Denes, Adam, Eggen, Bart BJL, Eyo, Ukpong, Galea, Elena, Garel, Sonia, Ginhoux, Florent, Glass, Christopher K, Gokce, Ozgun, Gomez-Nicola, Diego, González, Berta, Gordon, Siamon, Graeber, Manuel MB, Greenhalgh, Andrew AD, Gressens, Pierre, Greter, Melanie, Gutmann, David DH, Haass, Christian, Heneka, Michael MT, Heppner, Frank FL, Hong, Soyon, Hume, David DA, Jung, Steffen, Kettenmann, Helmut, Kipnis, Jonathan, Koyama, Ryuta, Lemke, Greg, Lynch, Marina, Majewska, Ania, Malcangio, Marzia, Malm, Tarja, Mancuso, Renzo, Masuda, Takahiro, Matteoli, Michela, McColl, Barry W, Miron, Veronique E, Molofsky, Anna Victoria, Monje, Michelle, Mracsko, Eva, Nadjar, Agnes, Neher, Jonas JJ, Neniskyte, Urte, Neumann, Frank Harald, Noda, Mami, Peng, Bo, Peri, Francesca, Perry, Hugh VH, Popovich, Phillip PG, Pridans, Clare, Priller, Josef, Prinz, Marco, Ragozzino, Davide, Ransohoff, Richard M, Salter, Michael W, Schaefer, Anne, Schafer, Dorothy P, Schwartz, Michal, Simons, Mikael, Smith, Cody J, Streit, Wolfgang WJ, Tay, Tuan Leng, Tsai, Li-Huei, Verkhratsky, Alexei, von Bernhardi, Rommy, Wake, Hiroaki, Wittamer, Valérie, Wolf, Susanne A, Wu, Long-Jun, Wyss-Coray, Tony, Paolicelli, Rosa RC, Sierra, Amanda, Stevens, Beth, Tremblay, Marie-Eve, Aguzzi, Adriano, Ajami, Bahareh, Amit, Ido, Audinat, Etienne, Bechmann, Ingo, Bennett, Mariko, Bennett, Frederick, Bessis, Alain, Biber, Knut, Bilbo, Staci, Blurton-Jones, Mathew, Boddeke, Erik, Brites, Dora, Brône, Bert, Brown, Guy C, Butovsky, Oleg, Carson, Monica J, Castellano, Bernardo, Colonna, Marco, Cowley, Sally A, Cunningham, Colm, Davalos, Dimitrios, De Jager, Philip L, De Strooper, Bart, Denes, Adam, Eggen, Bart BJL, Eyo, Ukpong, Galea, Elena, Garel, Sonia, Ginhoux, Florent, Glass, Christopher K, Gokce, Ozgun, Gomez-Nicola, Diego, González, Berta, Gordon, Siamon, Graeber, Manuel MB, Greenhalgh, Andrew AD, Gressens, Pierre, Greter, Melanie, Gutmann, David DH, Haass, Christian, Heneka, Michael MT, Heppner, Frank FL, Hong, Soyon, Hume, David DA, Jung, Steffen, Kettenmann, Helmut, Kipnis, Jonathan, Koyama, Ryuta, Lemke, Greg, Lynch, Marina, Majewska, Ania, Malcangio, Marzia, Malm, Tarja, Mancuso, Renzo, Masuda, Takahiro, Matteoli, Michela, McColl, Barry W, Miron, Veronique E, Molofsky, Anna Victoria, Monje, Michelle, Mracsko, Eva, Nadjar, Agnes, Neher, Jonas JJ, Neniskyte, Urte, Neumann, Frank Harald, Noda, Mami, Peng, Bo, Peri, Francesca, Perry, Hugh VH, Popovich, Phillip PG, Pridans, Clare, Priller, Josef, Prinz, Marco, Ragozzino, Davide, Ransohoff, Richard M, Salter, Michael W, Schaefer, Anne, Schafer, Dorothy P, Schwartz, Michal, Simons, Mikael, Smith, Cody J, Streit, Wolfgang WJ, Tay, Tuan Leng, Tsai, Li-Huei, Verkhratsky, Alexei, von Bernhardi, Rommy, Wake, Hiroaki, Wittamer, Valérie, Wolf, Susanne A, Wu, Long-Jun, and Wyss-Coray, Tony

Abstract

Microglial research has advanced considerably in recent decades yet has been constrained by a rolling series of dichotomies such as "resting versus activated" and "M1 versus M2." This dualistic classification of good or bad microglia is inconsistent with the wide repertoire of microglial states and functions in development, plasticity, aging, and diseases that were elucidated in recent years. New designations continuously arising in an attempt to describe the different microglial states, notably defined using transcriptomics and proteomics, may easily lead to a misleading, although unintentional, coupling of categories and functions. To address these issues, we assembled a group of multidisciplinary experts to discuss our current understanding of microglial states as a dynamic concept and the importance of addressing microglial function. Here, we provide a conceptual framework and recommendations on the use of microglial nomenclature for researchers, reviewers, and editors, which will serve as the foundations for a future white paper., SCOPUS: re.j, info:eu-repo/semantics/published

Published
2022

11. Defining Microglial States and Nomenclature: A Roadmap to 2030

Author

Paolicelli, Rosa, primary, Sierra, Amanda, additional, Stevens, Beth, additional, Tremblay, Marie-Eve, additional, Aguzzi, Adriano, additional, Ajami, Bahareh, additional, Amit, Ido, additional, Audinat, Etienne, additional, Bechmann, Ingo, additional, Bennett, Mariko, additional, Bennett, Frederick, additional, Bessis, Alain, additional, Biber, Knut, additional, Bilbo, Staci, additional, Blurton-Jones, Mathew, additional, Boddeke, Erik, additional, Brites, Dora, additional, Brône, Bert, additional, Brown, Guy C., additional, Butovsky, Oleg, additional, Carson, Monica J., additional, Castellano, Bernardo, additional, Colonna, Marco, additional, Cowley, Sally A., additional, Cunningham, Colm, additional, Davalos, Dimitrios, additional, De Jager, Philip L., additional, De Strooper, Bart, additional, Dénes, Ádám, additional, Eggen, Bart J.L., additional, Eyo, Ukpong, additional, Galea, Elena, additional, Garel, Sonia, additional, Ginhoux, Florent, additional, Glass, Christopher K., additional, Gokce, Ozgun, additional, Gomez-Nicola, Diego, additional, González, Berta, additional, Gordon, Siamon, additional, Graeber, Manuel B., additional, Greenhalgh, Andrew D., additional, Gressens, Pierre, additional, Greter, Melanie, additional, Gutmann, David H., additional, Haass, Christian, additional, Heneka, Michael T., additional, Heppner, Frank, additional, Hong, Soyon, additional, Jung, Steffen, additional, Kettenmann, Helmut, additional, Kipnis, Jonathan, additional, Koyama, Ryuta, additional, Lemke, Greg, additional, Lynch, Marina, additional, Majewska, Ania, additional, Malcangio, Marzia, additional, Malm, Tarja, additional, Mancuso, Renzo, additional, Matteoli, Michela, additional, McColl, Barry, additional, Miron, Veronique E., additional, Molofsky, Anna Victoria, additional, Monje, Michelle, additional, Mracsko, Eva, additional, Nadjar, Agnes, additional, Neher, Jonas J., additional, Neniskyte, Urte, additional, Neumann, Harald, additional, Noda, Mami, additional, Peng, Bo, additional, Peri, Francesca, additional, Perry, V. Hugh, additional, Popovich, Phillip G., additional, Priller, Josef, additional, Ragozzino, Davide, additional, Ransohoff, Richard M., additional, Salter, Michael W., additional, Schaefer, Anne, additional, Schafer, Dorothy P., additional, Schwartz, Michal, additional, Simons, Mikael, additional, Streit, Wolfgang J., additional, Tay, Tuan Leng, additional, Tsai, Li-Huei, additional, Verkhratsky, Alexei, additional, von Bernhardi, Rommy, additional, Wake, Hiroaki, additional, Wittamer, Valerie, additional, Wolf, Susanne A., additional, Wu, Long-Jun, additional, and Wyss-Coray, Tony, additional

Published
2022
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13. Adventitial stromal cells define group 2 innate lymphoid cell tissue niches

Author

Molofsky, Ari B, primary, Dahlgren, Madelene W, additional, Jones, Stephen W, additional, Dubinin, Alexandra, additional, Farhat, Sepideh, additional, Ortiz-Carpena, Jorge F, additional, Yu, Kevin S, additional, Lee, Katharine, additional, Wang, Chaoqun, additional, Molofsky, Anna Victoria R, additional, Tward, Aaron D, additional, Krummel, Matthew F, additional, and Peng, Tien, additional

Published
2019
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14. Variation among intact tissue samples reveals the core transcriptional features of human CNS cell classes.

Author

Kelley, Kevin, Kelley, Kevin, Nakao-Inoue, Hiromi, Molofsky, Anna Victoria, Oldham, Michael, Kelley, Kevin, Kelley, Kevin, Nakao-Inoue, Hiromi, Molofsky, Anna Victoria, and Oldham, Michael

Abstract

It is widely assumed that cells must be physically isolated to study their molecular profiles. However, intact tissue samples naturally exhibit variation in cellular composition, which drives covariation of cell-class-specific molecular features. By analyzing transcriptional covariation in 7,221 intact CNS samples from 840 neurotypical individuals, representing billions of cells, we reveal the core transcriptional identities of major CNS cell classes in humans. By modeling intact CNS transcriptomes as a function of variation in cellular composition, we identify cell-class-specific transcriptional differences in Alzheimers disease, among brain regions, and between species. Among these, we show that PMP2 is expressed by human but not mouse astrocytes and significantly increases mouse astrocyte size upon ectopic expression in vivo, causing them to more closely resemble their human counterparts. Our work is available as an online resource ( http://oldhamlab.ctec.ucsf.edu/ ) and provides a generalizable strategy for determining the core molecular features of cellular identity in intact biological systems.

Published
2018

15. Self -renewal of central nervous system stem cells.

Author

Molofsky, Anna Victoria

Subjects
Bmi-1, Central Nervous System, Self-renewal, Stem Cells
Abstract

Neural stem cells are defined by their ability to self-renew and undergo multilineage differentiation. We found that Bmi-1 is required for the self-renewal of central nervous system stem cells, and that in the absence of Bmi-1, stem cells become profoundly depleted by adulthood. Restricted neural progenitors from the forebrain proliferated normally in the absence of Bmi-1, revealing a molecular distinction between pathways that regulate stem cell self-renewal and those that regulate the proliferation of some types of restricted progenitors. In the absence of Bmi-1, both products of the Ink4a-Arf senescence-associated tumor suppressor locus (p16Ink4a and p19Arf) were upregulated in neural stem cells. Deletion of Ink4a or Arf from Bmi-1 -/- mice partially rescued stem cell self-renewal and stem cell frequency well as forebrain proliferation and gut neurogenesis. Arf deficiency, but not Ink4a deficiency, partially rescued cerebellum development, demonstrating regional differences in the sensitivity of progenitors to p16Ink4a and p19Arf. Deletion of both Ink4a and Arf did not affect the growth or survival of Bmi-1-/- mice or completely rescue neural development. Bmi-1 thus prevents the premature senescence of neural stem cells partly via the active repression of negative cell cycle regulators like p16 Ink4a and p19Arf. Overexpression of Bmi-1 in culture and in transgenic mice in vivo demonstrates that Bmi-1 is not only necessary, but also sufficient to promote self-renewal. Ink4a was also upregulated in stem cells during the course of normal aging. This correlated with an age-related depletion of CNS stem cells, as well decreased self-renewal in culture and subventricular zone proliferation in vivo. Deletion of Ink4a alleviated of some of these age-related phenotypes, indicating that the age-related increase in Ink4a expression was partly responsible for the decline in stem cell function and progenitor proliferation in old mice. Our studies of Bmi-1 have provided insight into a highly conserved regulator of stem cell self-renewal and postnatal maintenance. Ultimately, a better understanding of the molecular mechanisms that control the balance between self-renewal and senescence will further increase our understanding of how stem cells persist postnatally and contribute to tissue maintenance throughout adult life, while avoiding neoplastic transformation in old age.

Published
2005

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