@misc{HenzeHuettnerKochetal., author = {Henze, Henriette and H{\"u}ttner, S{\"o}ren S. and Koch, Philipp and Sch{\"u}ler, Svenja C. and Groth, Marco and von Eyss, Bj{\"o}rn and von Maltzahn, Julia}, title = {Denervation alters the secretome of myofibers and thereby affects muscle stem cell lineage progression and functionality}, series = {npj regenerative medicine}, volume = {9}, journal = {npj regenerative medicine}, number = {1}, publisher = {Nature Publishing Group UK}, address = {London}, issn = {2057-3995}, doi = {10.1038/s41536-024-00353-3}, pages = {1 -- 14}, abstract = {Skeletal muscle function crucially depends on innervation while repair of skeletal muscle relies on resident muscle stem cells (MuSCs). However, it is poorly understood how innervation affects MuSC properties and thereby regeneration of skeletal muscle. Here, we report that loss of innervation causes precocious activation of MuSCs concomitant with the expression of markers of myogenic differentiation. This aberrant activation of MuSCs after loss of innervation is accompanied by profound alterations on the mRNA and protein level. Combination of muscle injury with loss of innervation results in impaired regeneration of skeletal muscle including shifts in myogenic populations concomitant with delayed maturation of regenerating myofibers. We further demonstrate that loss of innervation leads to alterations in myofibers and their secretome, which then affect MuSC behavior. In particular, we identify an increased secretion of Osteopontin and transforming growth factor beta 1 (Tgfb1) by myofibers isolated from mice which had undergone sciatic nerve transection. The altered secretome results in the upregulation of early activating transcription factors, such as Junb , and their target genes in MuSCs. However, the combination of different secreted factors from myofibers after loss of innervation is required to cause the alterations observed in MuSCs after loss of innervation. These data demonstrate that loss of innervation first affects myofibers causing alterations in their secretome which then affect MuSCs underscoring the importance of proper innervation for MuSC functionality and regeneration of skeletal muscle.}, language = {en} } @misc{SchurigUmehHenzeetal., author = {Schurig, Mona and Umeh, Obinna and Henze, Henriette and Jung, Marie Juliane and Gresing, Lennart and Blanchard, Veronique and Maltzahn, Julia von and H{\"u}bner, Christian and Franzka, Patricia}, title = {Consequences of GMPPB deficiency for neuromuscular development and maintenance}, series = {Frontiers in Molecular Neuroscience}, volume = {17}, journal = {Frontiers in Molecular Neuroscience}, issn = {1662-5099}, doi = {10.3389/fnmol.2024.1356326}, abstract = {Guanosine diphosphate-mannose pyrophosphorylase B (GMPPB) catalyzes the conversion of mannose-1-phosphate and GTP to GDP-mannose, which is required as a mannose donor for the biosynthesis of glycan structures necessary for proper cellular functions. Mutations in GMPPB have been associated with variable neuromuscular disorders such as muscular dystrophy and myasthenic syndromes. Here, we report that GMPPB protein abundance increases during brain and skeletal muscle development, which is accompanied by an increase in overall protein mannosylation. To model the human disorder in mice, we generated heterozygous GMPPB KO mice using CRISPR/Cas9. While we were able to obtain homozygous KO mice from heterozygous matings at the blastocyst stage, homozygous KO embryos were absent beyond embryonic day E8.5, suggesting that the homozygous loss of GMPPB results in early embryonic lethality. Since patients with GMPPB loss-of-function manifest with neuromuscular disorders, we investigated the role of GMPPB in vitro. Thereby, we found that the siRNA-mediated knockdown of Gmppb in either primary myoblasts or the myoblast cell line C2C12 impaired myoblast differentiation and resulted in myotube degeneration. siRNA-mediated knockdown of Gmppb also impaired the neuron-like differentiation of N2A cells. Taken together, our data highlight the essential role of GMPPB during development and differentiation, especially in myogenic and neuronal cell types.}, language = {en} } @misc{MajchrzakHentschelHoenzkeetal., author = {Majchrzak, Karolina and Hentschel, Erik and H{\"o}nzke, Katja and Geithe, Christiane and Maltzahn, Julia von}, title = {We need to talk—how muscle stem cells communicate}, series = {Frontiers in Cell and Developmental Biology}, volume = {12}, journal = {Frontiers in Cell and Developmental Biology}, publisher = {Frontiers Media S.A.}, issn = {2296-634X}, doi = {10.3389/fcell.2024.1378548}, pages = {17}, abstract = {Skeletal muscle is one of the tissues with the highest ability to regenerate, a finely controlled process which is critically depending on muscle stem cells. Muscle stem cell functionality depends on intrinsic signaling pathways and interaction with their immediate niche. Upon injury quiescent muscle stem cells get activated, proliferate and fuse to form new myofibers, a process involving the interaction of multiple cell types in regenerating skeletal muscle. Receptors in muscle stem cells receive the respective signals through direct cell-cell interaction, signaling via secreted factors or cell-matrix interactions thereby regulating responses of muscle stem cells to external stimuli. Here, we discuss how muscle stem cells interact with their immediate niche focusing on how this controls their quiescence, activation and self-renewal and how these processes are altered in age and disease.}, language = {en} } @misc{LyuFuWilczoketal., author = {Lyu, Yu-Xuan and Fu, Qiang and Wilczok, Dominika and Ying, Kejun and King, Aaron and Antebi, Adam and Vojta, Aleksandar and Stolzing, Alexandra and Moskalev, Alexey and Georgievskaya, Anastasia and Maier, Andrea B. and Olsen, Andrea and Groth, Anja and Simon, Anna Katharina and Brunet, Anne and Jamil, Aisyah and Kulaga, Anton and Bhatti, Asif and Yaden, Benjamin and Pedersen, Bente Klarlund and Schumacher, Bj{\"o}rn and Djordjevic, Boris and Kennedy, Brian and Chen, Chieh and Huang, Christine Yuan and Correll, Christoph U. and Murphy, Coleen T. and Ewald, Collin Y. and Chen, Danica and Valenzano, Dario Riccardo and Sołdacki, Dariusz and Erritzoe, David and Meyer, David and Sinclair, David A. and Chini, Eduardo Nunes and Teeling, Emma C. and Morgen, Eric and Verdin, Eric and Vernet, Erik and Pinilla, Estefano and Fang, Evandro F. and Bischof, Evelyne and Mercken, Evi M. and Finger, Fabian and Kuipers, Folkert and Pun, Frank W. and Gy{\"u}lveszi, Gabor and Civiletto, Gabriele and Zmudze, Garri and Blander, Gil and Pincus, Harold A. and McClure, Joshua and Kirkland, James L. and Peyer, James and Justice, Jamie N. and Vijg, Jan and Gruhn, Jennifer R. and McLaughlin, Jerry and Mannick, Joan and Passos, Jo{\~a}o and Baur, Joseph A. and Betts-LaCroix, Joe and Sedivy, John M. and Speakman, John R. and Shlain, Jordan and Maltzahn, Julia von and Andreasson, Katrin I. and Moody, Kelsey and Palikaras, Konstantinos and Fortney, Kristen and Niedernhofer, Laura J. and Rasmussen, Lene Juel and Veenhoff, Liesbeth M. and Melton, Lisa and Ferrucci, Luigi and Quarta, Marco and Koval, Maria and Marinova, Maria and Hamalainen, Mark and Unfried, Maximilian and Ringel, Michael S. and Filipovic, Milos and Topors, Mourad and Mitin, Natalia and Roy, Nawal and Pintar, Nika and Barzilai, Nir and Binetti, Paolo and Singh, Parminder and Kohlhaas, Paul and Robbins, Paul D. and Rubin, Paul and Fedichev, Peter O. and Kamya, Petrina and Mu{\~n}oz-Canoves, Pura and de Cabo, Rafael and Faragher, Richard G. A. and Konrad, Rob and Ripa, Roberto and Mansukhani, Robin and B{\"u}ttner, Sabrina and Wickstr{\"o}m, Sara A. and Brunemeier, Sebastian and Jakimov, Sergey and Luo, Shan and Rosenzweig-Lipson, Sharon and Tsai, Shih-Yin and Dimmeler, Stefanie and Rando, Thomas A. and Peterson, Tim R. and Woods, Tina and Wyss-Coray, Tony and Finkel, Toren and Strauss, Tzipora and Gladyshev, Vadim N. and Longo, Valter D. and Dwaraka, Varun B. and Gorbunova, Vera and Acosta-Rodr{\´i}guez, Victoria A. and Sorrentino, Vincenzo and Sebastiano, Vittorio and Li, Wenbin and Suh, Yousin and Zhavoronkov, Alex and Scheibye-Knudsen, Morten and Bakula, Daniela}, title = {Longevity biotechnology: bridging AI, biomarkers, geroscience and clinical applications for healthy longevity}, series = {Aging}, volume = {16}, journal = {Aging}, number = {20}, publisher = {Impact Journals, LLC}, issn = {1945-4589}, doi = {10.18632/aging.206135}, pages = {12955 -- 12976}, language = {en} }