Article
Oncology
Romina Vardapour, Tim Kehl, Susanne Kneitz, Nicole Ludwig, Eckart Meese, Hans-Peter Lenhof, Manfred Gessler
Summary: NGS analysis revealed that mutations in the oncogene DGCR8 lead to altered miRNA expression and subsequently affect mRNA targets. The mutation only partially restored DGCR8 function, with impacts on cellular proliferation and differentiation, but was still able to complete embryoid body development.
Article
Neurosciences
Ekin Su Akdemir, Junsung Woo, Navish A. Bosquez Huerta, Brittney Lozzi, Andrew K. Groves, Akdes Serin Harmanci, Benjamin Deneen
Summary: Astrocytes, the most abundant glial cell in the brain, perform various tasks to support neuronal function and circuit activities. Through the study of astrocytes, a unique subpopulation called Lfng-GFP(+) astrocytes was identified, which occupies a distinct anatomic location in the spinal cord and directly contributes to neuronal function and sensory responses.
JOURNAL OF NEUROSCIENCE
(2022)
Article
Multidisciplinary Sciences
Hongjie Li, Jasper Janssens, Maxime De Waegeneer, Sai Saroja Kolluru, Kristofer Davie, Vincent Gardeux, Wouter Saelens, Fabrice David, Maria Brbic, Jure Leskovec, Colleen N. McLaughlin, Qijing Xie, Robert C. Jones, Katja Brueckner, Jiwon Shim, Sudhir Gopal Tattikota, Frank Schnorrer, Katja Rust, Todd G. Nystul, Zita Carvalho-Santos, Carlos Ribeiro, Soumitra Pal, Sharvani Mahadevaraju, Teresa M. Przytycka, Aaron M. Allen, Stephen F. Goodwin, Cameron W. Berry, Margaret T. Fuller, Helen White-Cooper, Erika L. Matunis, Stephen DiNardo, Anthony Galenza, Lucy Erin O'Brien, Julian A. T. Dow, Heinrich Jasper, Brian Oliver, Norbert Perrimon, Bart Deplancke, Stephen R. Quake, Liqun Luo, Stein Aerts
Summary: This study presents a single-cell atlas of the fruit fly Drosophila melanogaster, including 580,000 nuclei and annotations of over 250 distinct cell types. It serves as a valuable resource for the Drosophila community and provides a reference for studying genetic perturbations and disease models at single-cell resolution.
Article
Multidisciplinary Sciences
Hsin- Jen, Sunita Singh, Litao Tao, Helen R. Maunsell, Neil Segil, Andrew K. Groves
Summary: GFI1 is a transcription factor that plays a vital role in the differentiation and survival of hair cells in the cochlea. It promotes hair cell differentiation by enhancing ATOH1's transcriptional activity and acts as a direct transcriptional repressor to suppress non-hair cell genes.
SCIENTIFIC REPORTS
(2022)
Article
Cell Biology
Justine M. Renauld, Vibhuti Khan, Martin L. Basch
Summary: This study investigates the development and migration process of intermediate cells of the stria vascularis in the cochlea. These cells are crucial for normal hearing and start migrating into the lateral wall of the cochlea during embryonic development, continuing to proliferate postnatally.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Multidisciplinary Sciences
Pengbo Beck, Barbara Selle, Lukas Madenach, David T. W. Jones, Christian Vokuhl, Apurva Gopisetty, Arash Nabbi, Ines B. Brecht, Martin Ebinger, Jenny Wegert, Norbert Graf, Manfred Gessler, Stefan M. Pfister, Natalie Jaeger
Summary: Pediatric renal cell carcinomas (RCC) differ from their adult counterparts in histologic subtypes, clinical characteristics, and outcome. Whole-exome and transcriptome sequencing analyses revealed limited genomic overlap between pediatric RCC and adult RCC, even within the same histologic subtype. Recurrent somatic mutations in genes not previously reported in RCC were detected, and papillary pediatric RCCs exhibited distinct genomic subtypes compared to MiT-RCC and adult RCC.
Article
Allergy
Rajarshi Ghosh, Marita Bosticardo, Sunita Singh, Morgan Similuk, Ottavia M. Delmonte, Francesca Pala, Christine Peng, Colleen Jodarski, Michael D. Keller, Ivan K. Chinn, Andrew K. Groves, Luigi D. Notarangelo, Magdalena A. Walkiewicz, Javier Chinen, Vanessa Bundy
Summary: This study identified heterozygous loss-of-function variants in the FOXI3 gene as a possible genetic basis for nonsevere T-cell lymphopenia. Understanding the genetic etiology of this condition is crucial for clinical management and family planning.
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
(2022)
Article
Cell & Tissue Engineering
Pei-Ciao Tang, Li Chen, Sunita Singh, Andrew K. Groves, Karl R. Koehler, Xue Zhong Liu, Rick F. Nelson
Summary: In this study, we used stem cell-derived organoids to investigate the effects of Wnt signaling on early placodal ectoderm (PPE) differentiation. We found that modulating Wnt signaling can significantly increase the efficiency and reproducibility of inner ear organoid induction. Our data also reveal the critical role of Wnt signaling in the regionalization of PPE.
Review
Oncology
Amy L. Walz, Mariana Maschietto, Brian Crompton, Nicholas Evageliou, David Dix, Godelieve Tytgat, Manfred Gessler, David Gisselsson, Najat C. Daw, Jenny Wegert
Summary: The expanding knowledge on driver mutations for Wilms tumor (WT) and malignant rhabdoid tumor of the kidney (MRT) and various translocations for other pediatric renal tumors provides new possibilities for diagnosis and treatment. Additionally, there is growing data on prognostic factors that can help stratify WT treatment and improve outcomes. Incorporation of circulating tumor DNA/liquid biopsies can leverage the molecular landscape of these tumors and potentially aid in distinguishing renal tumors and evaluating intratumor heterogeneity.
PEDIATRIC BLOOD & CANCER
(2023)
Article
Biology
Amrita A. Iyer, Ishwar Hosamani, John D. Nguyen, Tiantian Cai, Sunita Singh, Melissa M. McGovern, Lisa Beyer, Hongyuan Zhang, Hsin- Jen, Rizwan Yousaf, Onur Birol, Jenny J. Sun, Russell S. Ray, Yehoash Raphael, Neil Segil, Andrew K. Groves, Brian S. Kim
Summary: Reprogramming of the cochlea with hair-cell-specific transcription factors such as ATOH1 has been proposed for treating hearing loss. However, the efficiency of hair cell reprogramming declines as the cochlea matures. A combination of ATOH1, GFI1, and POU4F3 can reprogram non-sensory cells of the cochlea to a hair cell fate, but the resulting cells are less mature compared to those generated at an earlier stage. Epigenetic accessibility and signaling from hair cells to supporting cells, including Notch signaling, are key factors that impede hair cell reprogramming in older animals.
Article
Multidisciplinary Sciences
Felix K. F. Kommoss, Anne-Sophie Chong, Anne-Laure Chong, Elke Pfaff, David T. W. Jones, Laura S. Hiemcke-Jiwa, Lennart A. Kester, Uta Flucke, Manfred Gessler, Daniel Schrimpf, Felix Sahm, Blaise A. Clarke, Colin J. R. Stewart, Yemin Wang, C. Blake Gilks, Friedrich Kommoss, David G. Huntsman, Ulrich Schueller, Christian Koelsche, W. Glenn McCluggage, Andreas von Deimling, William D. Foulkes
Summary: DICER1 syndrome is associated with a predisposition to multiple tumor types. In this study, the authors identify and characterize 3 molecular subgroups of mesenchymal tumors with DICER1 mutations. These DICER1-associated mesenchymal tumors include well-established clinicopathological tumor entities and can be further classified into low-grade mesenchymal tumor with DICER1 alteration (LGMT DICER1), sarcoma with DICER1 alteration (SARC DICER1), and primary intracranial sarcoma with DICER1 alteration (PIS DICER1). The findings provide insights into the classification of DICER1-associated neoplasms and suggest potential therapeutic approaches for affected patients.
NATURE COMMUNICATIONS
(2023)
Article
Developmental Biology
Ankita Thawani, Helen R. Maunsell, Hongyuan Zhang, Harinarayana Ankamreddy, Andrew K. Groves
Summary: The Foxi3 transcription factor plays an important role in early development by restricting progenitor cells at the neural plate border to a placodal and epidermal fate.
Article
Anatomy & Morphology
Harinarayana Ankamreddy, Ankita Thawani, Onur Birol, Hongyuan Zhang, Andrew K. Groves
Summary: This study successfully traced the development of Foxi3-expressing cells in mice through the introduction of Foxi3(GFP) and Foxi3(CreER) genes, and found that Foxi3 plays a crucial role in craniofacial, inner ear, tooth, and hair development.
DEVELOPMENTAL DYNAMICS
(2023)
Article
Oncology
Jenny Wegert, Anne Kristin Fischer, Balazs Palhazi, Taryn D. Treger, Caecilia Hilgers, Barbara Ziegler, Hyunchul Jung, Eva Juettner, Andreas Waha, Jorg Fuchs, Steven W. Warmann, Michael C. Fruehwald, Jochen Hubertus, Kathy Pritchard-Jones, Norbert Graf, Sam Behjati, Rhoikos Furtwaengler, Manfred Gessler, Christian Vokuhl
Summary: WTs are childhood cancers with diverse histology. TRIM28 mutations are associated with epithelial morphology and predisposition to WT. In this study, TRIM28 inactivation and predisposing mutations were investigated in a cohort of WTs with >2/3 epithelial cells. Loss of TRIM28 was found in 44.4% of cases and molecular analysis revealed sequence variants in each case, either homozygous or heterozygous with epigenetic silencing of the second allele. TRIM28-mutant tumors lacked WT-typical IGF2 alterations and driver events, but showed a high prevalence of perilobar nephrogenic rests. These findings suggest integrating TRIM28 immunohistochemical testing into diagnostic practice.
JOURNAL OF PATHOLOGY
(2023)
Article
Multidisciplinary Sciences
John D. Nguyen, Juan Llamas, Tuo Shi, J. Gage Crump, Andrew K. Groves, Neil Segil
Summary: Mammalian hair cells cannot regenerate in adulthood, but can regenerate in embryonic and neonatal stages through the direct transdifferentiation of neighboring supporting cells. This regeneration potential is lost due to DNA methylation and chromatin accessibility changes in the supporting cells as they mature. Understanding these epigenetic modifications may provide insights for future hearing restoration therapies.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)