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2. Fly Cell Atlas: A single-nucleus transcriptomic atlas of the adult fruit fly.

Author

Li, Hongjie, Janssens, Jasper, De Waegeneer, Maxime, Kolluru, Sai Saroja, Davie, Kristofer, Gardeux, Vincent, Saelens, Wouter, David, Fabrice PA, Brbić, Maria, Spanier, Katina, Leskovec, Jure, McLaughlin, Colleen N, Xie, Qijing, Jones, Robert C, Brueckner, Katja, Shim, Jiwon, Tattikota, Sudhir Gopal, Schnorrer, Frank, Rust, Katja, Nystul, Todd G, Carvalho-Santos, Zita, Ribeiro, Carlos, Pal, Soumitra, Mahadevaraju, Sharvani, Przytycka, Teresa M, Allen, Aaron M, Goodwin, Stephen F, Berry, Cameron W, Fuller, Margaret T, White-Cooper, Helen, Matunis, Erika L, DiNardo, Stephen, Galenza, Anthony, O'Brien, Lucy Erin, Dow, Julian AT, FCA Consortium§, Jasper, Heinrich, Oliver, Brian, Perrimon, Norbert, Deplancke, Bart, Quake, Stephen R, Luo, Liqun, Aerts, Stein, Agarwal, Devika, Ahmed-Braimah, Yasir, Arbeitman, Michelle, Ariss, Majd M, Augsburger, Jordan, Ayush, Kumar, Baker, Catherine C, Banisch, Torsten, Birker, Katja, Bodmer, Rolf, Bolival, Benjamin, Brantley, Susanna E, Brill, Julie A, Brown, Nora C, Buehner, Norene A, Cai, Xiaoyu Tracy, Cardoso-Figueiredo, Rita, Casares, Fernando, Chang, Amy, Clandinin, Thomas R, Crasta, Sheela, Desplan, Claude, Detweiler, Angela M, Dhakan, Darshan B, Donà, Erika, Engert, Stefanie, Floc'hlay, Swann, George, Nancy, González-Segarra, Amanda J, Groves, Andrew K, Gumbin, Samantha, Guo, Yanmeng, Harris, Devon E, Heifetz, Yael, Holtz, Stephen L, Horns, Felix, Hudry, Bruno, Hung, Ruei-Jiun, Jan, Yuh Nung, Jaszczak, Jacob S, Jefferis, Gregory SXE, Karkanias, Jim, Karr, Timothy L, Katheder, Nadja Sandra, Kezos, James, Kim, Anna A, Kim, Seung K, Kockel, Lutz, Konstantinides, Nikolaos, Kornberg, Thomas B, Krause, Henry M, Labott, Andrew Thomas, Laturney, Meghan, Lehmann, Ruth, Leinwand, Sarah, Li, Jiefu, and Li, Joshua Shing Shun

Subjects
FCA Consortium§, Cell Nucleus, Animals, Drosophila melanogaster, Drosophila Proteins, Transcription Factors, Gene Expression Regulation, Sex Characteristics, Genes, Insect, Databases, Genetic, Female, Male, Gene Regulatory Networks, Single-Cell Analysis, Transcriptome, RNA-Seq, Biotechnology, Genetics, 1.1 Normal biological development and functioning, Underpinning research, Generic health relevance, General Science & Technology
Abstract

For more than 100 years, the fruit fly Drosophila melanogaster has been one of the most studied model organisms. Here, we present a single-cell atlas of the adult fly, Tabula Drosophilae, that includes 580,000 nuclei from 15 individually dissected sexed tissues as well as the entire head and body, annotated to >250 distinct cell types. We provide an in-depth analysis of cell type-related gene signatures and transcription factor markers, as well as sexual dimorphism, across the whole animal. Analysis of common cell types between tissues, such as blood and muscle cells, reveals rare cell types and tissue-specific subtypes. This atlas provides a valuable resource for the Drosophila community and serves as a reference to study genetic perturbations and disease models at single-cell resolution.

Published
2022

3. MANF delivery improves retinal homeostasis and cell replacement therapies in ageing mice

Author

Neves, Joana, Chirco, Kathleen R, Cedron-Craft, Wendy, Chew, Shereen, Zhu, Jie, Jasper, Heinrich, and Lamba, Deepak A

Subjects
Biomedical and Clinical Sciences, Ophthalmology and Optometry, Neurosciences, Eye Disease and Disorders of Vision, Aging, Eye, Medical and Health Sciences, Gerontology, Biomedical and clinical sciences, Health sciences
Abstract

Ageing is a major risk factor for vision loss, and inflammation is an important contributor to retinal disease in the elderly. Regenerative medicine based on cell replacement strategies has emerged in recent years as a promising approach to restore vision. However, how the ageing process affects retinal homeostasis and inflammation in the retina and how this may impose a limitation to the success of such interventions remains unknown. Here we report that, in mice and humans, retinal ageing is associated with a reduction in MANF protein levels, specifically in the choroid, where increased densities of activated macrophages can be detected. We further show that the retina of old wild type mice, in the absence of any other genetic alteration, has limited homeostatic capacity after damage imposed by light exposure and reduced engraftment efficiency of exogenously supplied photoreceptors. Finally, we show that supplementation of MANF recombinant protein can improve retinal homeostasis and repair capacity in both settings, correlating with reduced numbers of activated macrophages in the old retina. Our work identifies age-related alterations in retinal homeostasis, independent of genetic alterations, leading to age-related retinal inflammation and damage susceptibility. We suggest that MANF therapy is a potential intervention to maintain retinal homeostasis in the elderly and improve the success of retinal regenerative therapies applied to aged individuals.

Published
2020

4. Obligate role for Rock1 and Rock2 in adult stem cell viability and function

Author

Sambandam, Arivazhagan, Storm, Elaine, Tauc, Helen, Hackney, Jason A., Garfield, David, Caplazi, Patrick, Liu, John, Zhang, Juan, Zhang, Hua, Duggan, Jeff, Jeet, Surinder, Gierke, Sarah, Chang, Patrick, Wu, Xiumin, Newman, Robert, Tam, Lucinda, Alcantar, Tuija, Wang, Lifen, Roose-Girma, Meron, Modrusan, Zora, Lee, Wyne P., Jasper, Heinrich, de Sauvage, Frederic, and Pappu, Rajita

Published
2023
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6. In vivo partial reprogramming alters age-associated molecular changes during physiological aging in mice

Author

Browder, Kristen C., Reddy, Pradeep, Yamamoto, Mako, Haghani, Amin, Guillen, Isabel Guillen, Sahu, Sanjeeb, Wang, Chao, Luque, Yosu, Prieto, Javier, Shi, Lei, Shojima, Kensaku, Hishida, Tomoaki, Lai, Zijuan, Li, Qingling, Choudhury, Feroza K., Wong, Weng R., Liang, Yuxin, Sangaraju, Dewakar, Sandoval, Wendy, Esteban, Concepcion Rodriguez, Delicado, Estrella Nuñez, Garcia, Pedro Guillen, Pawlak, Michal, Vander Heiden, Jason A., Horvath, Steve, Jasper, Heinrich, and Izpisua Belmonte, Juan Carlos

Published
2022
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7. Targeting the Hippo pathway in cancers via ubiquitination dependent TEAD degradation

Author

Pham, Trang H., primary, Pahuja, Kanika Bajaj, additional, Hagenbeek, Thijs J., additional, Zbieg, Jason, additional, Noland, Cameron L., additional, Pham, Victoria C., additional, Yao, Xiaosai, additional, Rose, Christopher M., additional, Browder, Kristen, additional, Lee, Ho-June, additional, Yu, Mamie, additional, Liang-Chu, May, additional, Martin, Scott, additional, Verschueren, Erik, additional, Li, Jason, additional, Kubala, Marta H., additional, Fong, Rina, additional, Lorenzo, Maria, additional, Beroza, Paul, additional, Hsu, Peter, additional, Paul, Sayantanee, additional, Villemure, Elisia, additional, Lee, Wendy, additional, Cheung, Tommy K., additional, Clausen, Saundra, additional, Lacap, Jennifer, additional, Liang, Yuxin, additional, Cheng, Jason, additional, Schmidt, Steve, additional, Modrusan, Zora, additional, Cohen, Michael, additional, Crawford, James, additional, Jasper, Heinrich, additional, Ashworth, Alan, additional, Lill, Jennie R., additional, Malek, Shiva, additional, Rudolph, Joachim, additional, Wertz, Ingrid E., additional, Chang, Matthew T., additional, Ye, Xin, additional, and Dey, Anwesha, additional

Published
2024
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10. Immune modulation by MANF promotes tissue repair and regenerative success in the retina

Author

Neves, Joana, Zhu, Jie, Sousa-Victor, Pedro, Konjikusic, Mia, Riley, Rebeccah, Chew, Shereen, Qi, Yanyan, Jasper, Heinrich, and Lamba, Deepak A

Subjects
Stem Cell Research, Eye Disease and Disorders of Vision, Neurosciences, Regenerative Medicine, Development of treatments and therapeutic interventions, 1.1 Normal biological development and functioning, Underpinning research, 5.2 Cellular and gene therapies, 2.1 Biological and endogenous factors, Aetiology, Eye, Animals, Drosophila Proteins, Drosophila melanogaster, Egg Proteins, Evolution, Molecular, Gene Expression Profiling, Hemocytes, Immunity, Innate, Immunomodulation, Mice, Mice, Inbred C57BL, Models, Animal, Nerve Growth Factors, Neuroprotective Agents, Photoreceptor Cells, Invertebrate, Photoreceptor Cells, Vertebrate, Platelet-Derived Growth Factor, Recombinant Proteins, Retina, Retinal Degeneration, Signal Transduction, Wound Healing, General Science & Technology
Abstract

Regenerative therapies are limited by unfavorable environments in aging and diseased tissues. A promising strategy to improve success is to balance inflammatory and anti-inflammatory signals and enhance endogenous tissue repair mechanisms. Here, we identified a conserved immune modulatory mechanism that governs the interaction between damaged retinal cells and immune cells to promote tissue repair. In damaged retina of flies and mice, platelet-derived growth factor (PDGF)-like signaling induced mesencephalic astrocyte-derived neurotrophic factor (MANF) in innate immune cells. MANF promoted alternative activation of innate immune cells, enhanced neuroprotection and tissue repair, and improved the success of photoreceptor replacement therapies. Thus, immune modulation is required during tissue repair and regeneration. This approach may improve the efficacy of stem-cell-based regenerative therapies.

Published
2016

11. Author response: Nicotinic acetylcholine receptor signaling maintains epithelial barrier integrity

Author

Katheder, Nadja S, primary, Browder, Kristen C, additional, Chang, Diana, additional, De Maziere, Ann, additional, Kujala, Pekka, additional, van Dijk, Suzanne, additional, Klumperman, Judith, additional, Lu, Tzu-Chiao, additional, Li, Hongjie, additional, Lai, Zijuan, additional, Sangaraju, Dewakar, additional, and Jasper, Heinrich, additional

Published
2023
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12. Targeting the Hippo pathway in cancers via ubiquitination dependent TEAD degradation

Author

Pham, Trang H, primary, Pahuja, Kanika Bajaj, additional, Hagenbeek, Thijs J, additional, Zbieg, Jason, additional, Noland, Cameron L, additional, Pham, Victoria C, additional, Yao, Xiaosai, additional, Rose, Christopher M, additional, Browder, Kristen C, additional, Lee, Ho-June, additional, Yu, Mamie, additional, Liang-Chu, May, additional, Martin, Scott E, additional, Verschueren, Erik, additional, Li, Jason, additional, Kubala, Marta H, additional, Fong, Rina, additional, Lorenzo, Maria, additional, Beroza, Paul, additional, Hsu, Peter, additional, Paul, Sayantanee, additional, Villemure, Elisia, additional, Lee, Wendy, additional, Cheung, Tommy, additional, Clausen, Saundra, additional, Lacap, Jennifer, additional, Liang, Yuxin, additional, Cheng, Jason, additional, Schmidt, Steve, additional, Modrusan, Zora, additional, Cohen, Michael S, additional, Crawford, James, additional, Jasper, Heinrich, additional, Ashworth, Alan, additional, Lill, Jennie R, additional, Malek, Shiva, additional, Rudolph, Joachim, additional, Wertz, Ingrid E, additional, Chang, Matthew, additional, Ye, Xin, additional, and Dey, Anwesha, additional

Published
2023
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19. Aging Fly Cell Atlas identifies exhaustive aging features at cellular resolution

Author

Lu, Tzu-Chiao, primary, Brbić, Maria, additional, Park, Ye-Jin, additional, Jackson, Tyler, additional, Chen, Jiaye, additional, Kolluru, Sai Saroja, additional, Qi, Yanyan, additional, Katheder, Nadja Sandra, additional, Cai, Xiaoyu Tracy, additional, Lee, Seungjae, additional, Chen, Yen-Chung, additional, Auld, Niccole, additional, Liang, Chung-Yi, additional, Ding, Sophia H., additional, Welsch, Doug, additional, D’Souza, Samuel, additional, Pisco, Angela Oliveira, additional, Jones, Robert C., additional, Leskovec, Jure, additional, Lai, Eric C., additional, Bellen, Hugo J., additional, Luo, Liqun, additional, Jasper, Heinrich, additional, Quake, Stephen R., additional, and Li, Hongjie, additional

Published
2023
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20. Abstract IA14: Host autophagy mediates organ wasting and nutrient mobilization for tumor growth

Author

Holland, Petter, primary, Schoborg, Todd Andrew, additional, Abramovich, Ifat, additional, Takáts, Szabolcs, additional, Dillard, Caroline, additional, Jain, Ashish, additional, O'Farrell, Fergal, additional, Schultz, Sebastian Wolfgang, additional, Hagopian, William M., additional, Quintana, Eduardo Martin, additional, Ng, Rachel, additional, Katheder, Nadja Sandra, additional, Rahman, Mohammed Mahidur, additional, Reis, José Gerardo Teles, additional, Brech, Andreas, additional, Jasper, Heinrich, additional, Rusan, Nasser M., additional, Jahren, Anne Hope, additional, Gottlieb, Eyal, additional, and Rusten, Tor Erik, additional

Published
2023
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21. NAD+ augmentation restores mitophagy and limits accelerated aging in Werner syndrome

Author

Fang, Evandro F., Hou, Yujun, Lautrup, Sofie, Jensen, Martin Borch, Yang, Beimeng, SenGupta, Tanima, Caponio, Domenica, Khezri, Rojyar, Demarest, Tyler G., Aman, Yahyah, Figueroa, David, Morevati, Marya, Lee, Ho-Joon, Kato, Hisaya, Kassahun, Henok, Lee, Jong-Hyuk, Filippelli, Deborah, Okur, Mustafa Nazir, Mangerich, Aswin, Croteau, Deborah L., Maezawa, Yoshiro, Lyssiotis, Costas A., Tao, Jun, Yokote, Koutaro, Rusten, Tor Erik, Mattson, Mark P., Jasper, Heinrich, Nilsen, Hilde, and Bohr, Vilhelm A.

Published
2019
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22. Suppressors of Superoxide-H2O2 Production at Site IQ of Mitochondrial Complex I Protect against Stem Cell Hyperplasia and Ischemia-Reperfusion Injury

Author

Brand, Martin D., Goncalves, Renata L.S., Orr, Adam L., Vargas, Leonardo, Gerencser, Akos A., Borch Jensen, Martin, Wang, Yves T., Melov, Simon, Turk, Carolina N., Matzen, Jason T., Dardov, Victoria J., Petrassi, H. Michael, Meeusen, Shelly L., Perevoshchikova, Irina V., Jasper, Heinrich, Brookes, Paul S., and Ainscow, Edward K.

Published
2016
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27. Aging Fly Cell Atlas Identifies Exhaustive Aging Features at Cellular Resolution

Author

Lu, Tzu-Chiao, primary, Brbić, Maria, additional, Park, Ye-Jin, additional, Jackson, Tyler, additional, Chen, Jiaye, additional, Kolluru, Sai Saroja, additional, Qi, Yanyan, additional, Katheder, Nadja Sandra, additional, Cai, Xiaoyu Tracy, additional, Lee, Seungjae, additional, Chen, Yen-Chung, additional, Auld, Niccole, additional, Welsch, Doug, additional, D’Souza, Samuel, additional, Pisco, Angela Oliveira, additional, Jones, Robert C., additional, Leskovec, Jure, additional, Lai, Eric C., additional, Bellen, Hugo J., additional, Luo, Liqun, additional, Jasper, Heinrich, additional, Quake, Stephen R., additional, and Li, Hongjie, additional

Published
2022
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32. Signal integration by [Ca.sup.2+] regulates intestinal stem-cell activity

Author

Deng, Hansong, Gerencser, Akos A., and Jasper, Heinrich

Subjects
Intestines -- Physiological aspects -- Health aspects, Stem cells -- Physiological aspects -- Health aspects, Homeostasis -- Physiological aspects -- Health aspects, Calcium, Dietary -- Health aspects -- Physiological aspects, Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

Somatic stem cells maintain tissue homeostasis by dynamically adjusting proliferation and differentiation in response to stress and metabolic cues. Here we identify [Ca.sup.2+] signalling as a central regulator of intestinal stem cell (ISC) activity in Drosophila. We show that dietary L-glutamate stimulates ISC division and gut growth. The metabotropic glutamate receptor (mGluR) is required in ISCs for this response, and for an associated modulation of cytosolic [Ca.sup.2+] oscillations that results in sustained high cytosolic [Ca.sup.2+] concentrations. High cytosolic [Ca.sup.2+] concentrations induce ISC proliferation by regulating Calcineurin and CREB-regulated transcriptional co-activator (Crtc). In response to a wide range of dietary and stress stimuli, ISCs reversibly transition between [Ca.sup.2+] oscillation states that represent poised or activated modes of proliferation, respectively. We propose that the dynamic regulation of intracellular [Ca.sup.2+] levels allows effective integration of diverse mitogenic signals in ISCs to adapt their proliferative activity to the needs of the tissue., Somatic stem cells can shift between quiescent and active states, and between asymmetric and symmetric division modes according to the regenerative need of a tissue (1-4). How stem cells decode [...]

Published
2015
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41. Host autophagy mediates organ wasting and nutrient mobilization for tumor growth

Author

Khezri, Rojyar, primary, Holland, Petter, additional, Schoborg, Todd Andrew, additional, Abramovich, Ifat, additional, Takáts, Szabolcs, additional, Dillard, Caroline, additional, Jain, Ashish, additional, O'Farrell, Fergal, additional, Schultz, Sebastian Wolfgang, additional, Hagopian, William M, additional, Quintana, Eduardo Martin, additional, Ng, Rachel, additional, Katheder, Nadja Sandra, additional, Rahman, Mohammed Mahidur, additional, Teles Reis, José Gerardo, additional, Brech, Andreas, additional, Jasper, Heinrich, additional, Rusan, Nasser M, additional, Jahren, Anne Hope, additional, Gottlieb, Eyal, additional, and Rusten, Tor Erik, additional

Published
2021
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43. Geohub: Sustainable Geomodeling

Author

Semmler , Georg, Schaeben , Helmut, and Jasper , Heinrich

Abstract

Digital 3D geomodels are becoming a routine tool for geoscientific research, engineering and surveying. Most models incorporate various datasets into a simplified virtual representation of reality. Turning the process of model building into something sustainable, so that future users can build on the results and insights provided by a given model raises a number of questions: • How can we assure that other users can reconstruct the same model given the required information? • How do we ensure that repetition of a construction using the same information yields the same geomodel, such that the process itself is reproducible? With Geohub we present a theoretical framework to represent a construction process of a geomodel. We represent a construction process as directed acylic hypergraph. Each node of this hypergraph represents a dataset used or generated as part of the construction process. Each hyperedge represents a construction step, that transforms a set of input datasets into a single possible intermediate output dataset. Construction steps consists of a generic representation, which is executable with a computer. This enables us to repeat a construction process to: • check if the construction of a geomodel is reproducible by comparing the results of different repetitions • update a geomodel with new input data by repeating the construction using the new dataset • generate different realisations of the same geomodel built by input dataset based on stochastic distributions. Eventually we present an implementation of this framework ensuring repeatability of the construction process and reproducibility of the geomodels constructed in this way.

Published
2021
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45. Author response: Age-related changes in polycomb gene regulation disrupt lineage fidelity in intestinal stem cells

Author

Tauc, Helen M, primary, Rodriguez-Fernandez, Imilce A, additional, Hackney, Jason A, additional, Pawlak, Michal, additional, Ronnen Oron, Tal, additional, Korzelius, Jerome, additional, Moussa, Hagar F, additional, Chaudhuri, Subhra, additional, Modrusan, Zora, additional, Edgar, Bruce A, additional, and Jasper, Heinrich, additional

Published
2021
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47. Host autophagy mediates organ wasting and nutrient mobilization for tumor growth

Author

Khezri, Rojyar, primary, Holland, Petter, additional, Schoborg, Todd Andrew, additional, Abramovich, Ifat, additional, Takats, Szabolcs, additional, Dillard, Caroline, additional, Jain, Ashish, additional, OFarrell, Fergal, additional, Schultz, Sebastian Wolfgang, additional, Hagopian, William M., additional, Quintana, Eduardo Martin, additional, Ng, Rachel, additional, Katheder, Nadja Sandra, additional, Rahman, Mohammed Mahidur, additional, Brech, Andreas, additional, Jasper, Heinrich, additional, Rusan, Nasser M., additional, Jahren, Anne Hope, additional, Gottlieb, Eyal, additional, and Rusten, Tor Erik, additional

Published
2020
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50. JNK extends life span and limits growth by antagonizing cellular and organism-wide responses to insulin signaling

Author

Mang C. Wang, Bohmann, Dirk, and Jasper, Heinrich

Subjects
Oxidative stress -- Research, Eukaryotes -- Genetic aspects, Genetic research, Biological sciences
Abstract

The transcription factor Foxo, which is inhibited by the insulin/IGF signaling (IIS), extends life span in conditions of low IIS activity but life span can also be increased by activating the stress-responsive Jun-N-terminal kinase (JNK) pathway. A model to explain the effects of stress and nutrition on longevity provides can be provided by the convergence of JNK signaling and IIS on Foxo.

Published
2005

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