Article
Geriatrics & Gerontology
Rebecca E. Schmitt, Aneesha Dasgupta, Paige C. Arneson-Wissink, Srijani Datta, Alexandra M. Ducharme, Jason D. Doles
Summary: Up to half of sepsis survivors suffer from chronic critical illness (CCI), which includes multiple physical and mental disabilities that hinder their return to regular activities. A study has shown that muscle stem cells (MuSCs) and muscle regeneration play crucial roles in post-sepsis muscle recovery and that sepsis triggers morphological, functional, and transcriptional changes in MuSCs.
JOURNAL OF CACHEXIA SARCOPENIA AND MUSCLE
(2023)
Article
Cell Biology
Hiroki Nagai, Luis Augusto Eijy Nagai, Sohei Tasaki, Ryuichiro Nakato, Daiki Umetsu, Erina Kuranaga, Masayuki Miura, Yuichiro Nakajima
Summary: Nutrient fluctuation induces dedifferentiation in Drosophila adult midgut and drives adaptive intestinal growth by converting enteroendocrine cells into functional intestinal stem cells.
DEVELOPMENTAL CELL
(2023)
Article
Immunology
Zhiqiang Wang, Zhou Lu, Shengli Lin, Jie Xia, Ziwen Zhong, Zhangjuan Xie, Yun Xing, Jingbo Qie, Mengxia Jiao, Yifan Li, Haoyu Wen, Pengyuan Zhao, Dan Zhang, Pinghong Zhou, Jiawen Qian, Feifei Luo, Luman Wang, Hongxiu Yu, Jie Liu, Jie Gu, Ronghua Liu, Yiwei Chu
Summary: A subset of B cells expressing leucine-tRNA-synthase-2 (LARS2) with a transforming growth factor-beta 1 (TGF-beta 1) regulatory feature has been identified in both mouse and human colorectal cancer (CRC). These cells exhibit a leucine nutrient preference and are located outside the tertiary lymphoid structure. They are associated with colorectal hyperplasia and shortened survival in CRC patients. A leucine diet can induce the generation of LARS B cells, while deletion of Lars2 gene or leucine blockage can repress CRC immunoevasion. Mechanistically, LARS2 regulates mitochondrial nicotinamide adenine dinucleotide (NAD(+)) regeneration and oxidative metabolism, involving the NAD-dependent protein deacetylase sirtuin-1 (SIRT1).
Article
Cell & Tissue Engineering
Sixia Huang, Paola Kuri, Yann Aubert, Megan Brewster, Ning Li, Olivia Farrelly, Gabriella Rice, Hyunjin Bae, Stephen Prouty, Tzvete Dentchev, Wenqin Luo, Brian C. Capell, Panteleimon Rompolas
Summary: Lgr6 epidermal stem cells play a crucial role in wound re-epithelialization and interact with nerves to regulate their fate. Loss of nerves affects the wound closure process, leading to recruitment of other stem cell populations for compensation.
Review
Cell Biology
Jingliang Gu, Wu Rao, Shaochuan Huo, Tianyou Fan, Minlei Qiu, Haixia Zhu, Deta Chen, Xiaoping Sheng
Summary: Osteoarthritis (OA) is a common musculoskeletal disease that is characterized by progressive loss of articular cartilage and other pathological changes. Non-coding RNAs (ncRNAs), especially miRNAs and lncRNAs, play vital roles in regulating cartilage homeostasis and the progression of OA. Changes in ncRNA expression levels can promote or decelerate OA progression through distinct molecular mechanisms. The potential of ncRNAs as diagnostic biomarkers, prognostic indicators, and therapeutic targets for OA has been emphasized.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Gastroenterology & Hepatology
Moritz Middelhoff, Giovanni Valenti, Lorenzo Tomassoni, Yosuke Ochiai, Bryana Belin, Ryota Takahashi, Ermanno Malagola, Henrik Nienhueser, Michael Finlayson, Yoku Hayakawa, Leah B. Zamechek, Bernhard W. Renz, C. Benedikt Westphalen, Michael Quante, Kara G. Margolis, Peter A. Sims, Pasquale Laise, Andrea Califano, Meenakshi Rao, Michael D. Gershon, Timothy C. Wang
Summary: The study identified different DCLK1-positive cell types in adult myenteric ganglia, which are resistant to acute injury but differ in their response to injury. Specifically, DCLK1-labeled glial-like cells showed significant transcriptional changes in response to injury and exhibited features resembling enteric neural precursor cells. These findings suggest the presence of reserve progenitor cells in the adult DCLK1 glial cell lineage, adding to the evidence of cellular plasticity in the adult enteric nervous system.
AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY
(2022)
Article
Multidisciplinary Sciences
Sheng Xing, Jin-Ze Tian, Shu-Hua Yang, Xue-Ting Huang, Yan-Fu Ding, Qian-Yun Lu, Jin-Shu Yang, Wei-Jun Yang
Summary: Blood vessels in adult mammals are highly organized and stable, but in cases of ischemic heart, c-Kit(+) cells play a crucial role in the development and homeostasis of cardiac endothelial cells. Setd4-expressing quiescent c-Kit(+) cells can regulate vascular endothelial cells and improve cardiac function in myocardial infarction injured mice. This suggests the potential for targeted treatments for cardiac ischemic injury by controlling the quiescence of c-Kit(+) cells through epigenetic mechanisms.
SCIENTIFIC REPORTS
(2021)
Article
Biochemistry & Molecular Biology
Hui Zhen, Mujie Huang, Mingyue Zheng, Lili Gao, Zepeng Guo, Qiuxiang Pang, Guoxiang Jin, Zhongjun Zhou
Summary: In this study, we investigated the expression pattern and functions of the conserved WTAP gene in planarians. Knocking down WTAP resulted in severe morphological defects and lethality within 20 days. Silencing WTAP promoted the proliferation of PiwiA+ cells but impaired the differentiation of various cell types. RNA-seq analysis revealed upregulation of H4, Histone-lysine N-methyltransferase-SETMAR like, and TNF receptor-associated factor 6 (TRAF6) upon WTAP knockdown. Knocking down TRAF6 partially rescued the tissue homeostasis and regeneration defects, suggesting that WTAP maintains planarian regeneration and homeostasis via TRAF6.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2023)
Article
Genetics & Heredity
Wenjuan Pu, Huan Zhu, Mingjun Zhang, Monika Pikiolek, Caner Ercan, Jie Li, Xiuzhen Huang, Ximeng Han, Zhenqian Zhang, Zan Lv, Yan Li, Kuo Liu, Lingjuan He, Xiuxiu Liu, Markus H. Heim, Luigi M. Terracciano, Jan S. Tchorz, Bin Zhou
Summary: Transitional liver progenitor cells (TLPCs), derived from biliary epithelial cells (BECs), differentiate into hepatocytes after severe liver damage. Notch and WNT/β-catenin signaling regulate the conversions of BEC-to-TLPC and TLPC-to-hepatocyte, respectively.
Review
Physiology
Jea Giezl Niedo Solidum, Youngjae Jeong, Francisco Heralde III, Dongsu Park
Summary: Skeletal stem/progenitor cells (SSPCs) play crucial roles in skeletal development, bone remodeling, and repair. Recent studies have revealed the presence of distinct SSPC populations in various skeletal compartments. The regulatory mechanisms for these cells differ based on their cellular and matrix environment, embryonic origin, and adjacent tissue structures. Understanding these regulatory differences is important for discovering novel treatment approaches for bone repair.
FRONTIERS IN PHYSIOLOGY
(2023)
Review
Immunology
Stefan Vogt, Jochen Mattner
Summary: Innate T lymphocytes like NKT cells are crucial in recognizing and eliminating microbial infections. They release cytokines explosively upon TCR engagement, regulate immune cell migration and activation, and bridge the gap between innate and adaptive immune responses.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Yue Ke, Jintao Wu, Yu Ye, Xiaolan Zhang, Tingjie Gu, Yanqiu Wang, Fei Jiang, Jinhua Yu
Summary: Feather keratin-montmorillonite nanocomposite hydrogels can promote bone tissue regeneration and improve the biocompatibility and mechanical properties of hydrogels. They regulate the BMP/SMAD signaling pathway to stimulate osteogenic differentiation of endogenous stem cells and promote bone defect healing, making them a promising candidate in bone tissue engineering.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2023)
Article
Cell Biology
Zhen Jiang, Teng Feng, Zhengkai Lu, Yuanxin Wei, Jufeng Meng, Chao-Po Lin, Bin Zhou, Chen Liu, Hui Zhang
Summary: Studies have shown that cardiac mesenchymal cells (MCs) contribute to the formation of cardiac adipocytes (CAs), with PDGFRb(+) MCs identified as the major source. PDGFRb(+) cells are heterogeneous, and PDGFRa(+)PDGFRb(+) double-positive periendothelial fibroblasts play a significant role in contributing to intramyocardial adipocytes.
Article
Multidisciplinary Sciences
Daniela Nasteska, Nicholas H. F. Fine, Fiona B. Ashford, Federica Cuozzo, Katrina Viloria, Gabrielle Smith, Aisha Dahir, Peter W. J. Dawson, Yu-Chiang Lai, Aimee Bastidas-Ponce, Mostafa Bakhti, Guy A. Rutter, Remi Fiancette, Rita Nano, Lorenzo Piemonti, Heiko Lickert, Qiao Zhou, Ildem Akerman, David J. Hodson
Summary: Transcriptionally mature and immature beta-cells coexist in adult islets, with differences in PDX1 and MAFA expression contributing to islet operation, leading to defects in metabolism, ionic fluxes, and insulin secretion when more PDX1(HIGH) and MAFA(HIGH) beta-cells are present. Dysregulation of gene pathways involved in metabolic processes is observed with increased numbers of PDX1(HIGH) and MAFA(HIGH) beta-cells, and differences in PDX1 and MAFA expression are dependent on islet Ca2+ signaling patterns.
NATURE COMMUNICATIONS
(2021)
Article
Cell Biology
Gurmannat Kalra, Daniell Lenz, Dunia Abdul-Aziz, Craig Hanna, Mahashweta Basu, Brian R. Herb, Carlo Colantuoni, Beatrice Milon, Madhurima Saxena, Amol C. Shetty, Ronna Hertzano, Ramesh A. Shivdasani, Seth A. Ament, Albert S. B. Edge
Summary: In this study, we examined the changes in chromatin accessibility and transcriptional programs during the differentiation of cochlear hair cells from postmitotic supporting cells using organoids. We identified Lgr5+ cells as the progenitors for hair cells and revealed the gene regulatory networks involved in their development. The analysis also predicted the involvement of additional regulatory factors in hair cell regeneration. This study provides important insights into the signals for hair cell regeneration from mammalian supporting cells.
Article
Gastroenterology & Hepatology
Henrik Nienhuser, Woosook Kim, Ermanno Malagola, Tuo Ruan, Giovanni Valenti, Moritz Middelhoff, Adam Bass, Channing J. Der, Yoku Hayakawa, Timothy C. Wang
Summary: The study revealed that gastric Mist1+ isthmus cells are activated in response to injury and inflammation, playing a crucial role in the regeneration of gastric glands through the Wnt5a pathway.
Article
Biochemistry & Molecular Biology
Qiaosi Tang, Ashley Lento, Kensuke Suzuki, Gizem Efe, Tatiana Karakasheva, Apple Long, Veronique Giroux, Mirazul Islam, E. Paul Wileyto, Andres J. Klein-Szanto, Hiroshi Nakagawa, Adam Bass, Anil K. Rustgi
Summary: The study reveals that TP53 mutation is the most common in ESCC, while Rab11-FIP1 gene is significantly downregulated in mutant p53 tumor cells. Genetic knockdown of Rab11-FIP1 results in increased organoid size and promotes tumor cell invasion through mutant p53.
Article
Oncology
Jason R. Pitarresi, Robert J. Norgard, Anna M. Chiarella, Kensuke Suzuki, Basil Bakir, Varun Sahu, Jinyang Li, Jun Zhao, Benoit Marchand, Maximilian D. Wengyn, Antony Hsieh, Il-Kyu Kim, Amy Zhang, Karine Sellin, Vivian Lee, Shigetsugu Takano, Yoji Miyahara, Masayuki Ohtsuka, Anirban Maitra, Faiyaz Notta, Richard Kremer, Ben Z. Stanger, Anil K. Rustgi
Summary: The amplification of PTHrP in pancreatic cancer is related to tumor growth and metastasis, and its loss can significantly reduce tumor burden, eliminate metastasis, and enhance overall survival. Targeting PTHrP activity may be a novel therapeutic approach for treating pancreatic cancer.
Article
Gastroenterology & Hepatology
Magdalena Kasendra, Misty Troutt, Taylor Broda, W. Clark Bacon, Timothy C. Wang, Joyce C. Niland, Michael A. Helmrath
Summary: Recent advances in intestinal organoid research have shown promising therapeutic potential for treating severely injured or diseased bowels using induced pluripotent stem cell (iPSC)-derived organoids. However, careful planning, significant resources, and collaboration between experts from various disciplines are required to address the safety and efficacy challenges in transitioning from laboratory discovery to first-in-human clinical trials.
AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY
(2021)
Letter
Gastroenterology & Hepatology
Woosook Kim, Timothy C. Wang
Article
Cell Biology
Qiaosi Tang, Gizem Efe, Anna M. Chiarella, Jessica Leung, Maoting Chen, Taiji Yamazoe, Zhenyi Su, Jason R. Pitarresi, Jinyang Li, Mirazul Islam, Tatiana Karakasheva, Andres J. Klein-Szanto, Samuel Pan, Jianhua Hu, Shoji Natsugoe, Wei Gu, Ben Z. Stanger, Kwok-K Wong, J. Alan Diehl, Adam J. Bass, Hiroshi Nakagawa, Maureen E. Murphy, Anil K. Rustgi
Summary: Esophageal squamous cell carcinoma (ESCC) is a deadly cancer that often metastasizes to the lungs. The study investigated how the p53R175H mutation regulates metastasis in ESCC. Depletion of Trp53R172H in primary tumor cell lines led to reduced invasion and lung metastasis, with the YAP-BIRC5 axis identified as a potential mediator. Survivin, a protein encoded by BIRC5, was found to be upregulated by Trp53R172H and associated with increased metastasis in GI cancers. These findings provide new insights into mutant p53-mediated metastasis.
GENES & DEVELOPMENT
(2021)
Editorial Material
Cell & Tissue Engineering
Jason R. Pitarresi, Anil K. Rustgi
Summary: In this issue, two studies developed human stem-cell-derived organoid culture systems to mimic pancreatic acinar and ductal lineages, offering opportunities to study cellular plasticity and transformation in pancreatic cancer initiation and progression.
Article
Biochemistry & Molecular Biology
Robert J. Norgard, Jason R. Pitarresi, Ravikanth Maddipati, Nicole M. Aiello-Couzo, David Balli, Jinyang Li, Taiji Yamazoe, Maximilian D. Wengyn, Ian D. Millstein, Ian W. Folkert, Derick N. Rosario-Berrios, Il-Kyu Kim, Jared B. Bassett, Riley Payne, Corbett T. Berry, Xiaodong Feng, Kathryn Sun, Michele Cioffi, Priyanka Chakraborty, Mohit Kumar Jolly, J. Silvio Gutkind, David Lyden, Bruce D. Freedman, J. Kevin Foskett, Anil K. Rustgi, Ben Z. Stanger
Summary: Epithelial-mesenchymal transition (EMT) is a form of cellular plasticity that gives tumor cells invasiveness and alters their sensitivity to drugs, posing a challenge to cancer therapy. Carcinoma cells in a partial EMT state have higher metastatic capacity than those in extreme states. Prolonged calcium signaling induces a partial EMT characterized by the internalization of membrane-associated E-cadherin and increased migration and invasion abilities.
Article
Oncology
Ravikanth Maddipati, Robert J. Norgard, Timour Baslan, Komal S. Rathi, Amy Zhang, Asal Saeid, Taku Higashihara, Feng Wu, Angad Kumar, Valli Annamalai, Saurav Bhattacharya, Pichai Raman, Christian A. Adkisson, Jason R. Pitarresi, Maximilian D. Wengyn, Taiji Yamazoe, Jinyang Li, David Balli, Michael J. LaRiviere, Tuong-Vi C. Ngo, Ian W. Folkert, Ian D. Millstein, Jonathan Bermeo, Erica L. Carpenter, John C. McAuliffe, Maja H. Oktay, Rolf A. Brekken, Scott W. Lowe, Christine A. Iacobuzio-Donahue, Faiyaz Notta, Ben Z. Stanger
Summary: This study investigated the biological and functional differences driving metastasis in patients with PDAC using a mouse model. The findings revealed an association between the extent of metastasis and gene amplification or transcriptional upregulation of the MYC gene and its downstream targets. Functional experiments demonstrated that MYC promotes metastasis by recruiting tumor-associated macrophages. Further analysis showed that metastatic progression in human PDAC is associated with activation of MYC signaling pathways and MYC amplifications in metastatic patients specifically.
Editorial Material
Engineering, Biomedical
Jason R. Pitarresi, Anil K. Rustgi
Summary: The use of a microwell chip can facilitate the differentiation of aggregates of human induced pluripotent stem cells into pancreatic-duct-like organoids and characterize the differentiation process at the single-cell level.
NATURE BIOMEDICAL ENGINEERING
(2021)
Article
Multidisciplinary Sciences
Tatiana A. Karakasheva, Joel T. Gabre, Uma M. Sachdeva, Ricardo Cruz-Acuna, Eric W. Lin, Maureen DeMarshall, Gary W. Falk, Gregory G. Ginsberg, Zhaohai Yang, Michele M. Kim, Eric S. Diffenderfer, Jason R. Pitarresi, Jinyang Li, Amanda B. Muir, Kathryn E. Hamilton, Hiroshi Nakagawa, Adam J. Bass, Anil K. Rustgi
Summary: This study aimed to evaluate the use of esophageal cancer PDOs created from treatment-naive patients in predicting and modeling clinical outcomes. Results showed that PDOs could mirror clinical responses, suggesting their potential value in predicting clinical response to new therapeutic approaches. Future clinical trials should further explore the use of pre-treatment PDOs for personalized therapies in patients with esophageal adenocarcinoma.
SCIENTIFIC REPORTS
(2021)
Editorial Material
Biochemistry & Molecular Biology
Ermanno Malagola, Yoku Hayakawa, Timothy C. Wang
Summary: Recent research has identified distinct roles for Lgr4 and Lgr5 in directing gland reconstitution following H. pylori infection, shedding new light on the complexities of Rspo signaling during gastric regeneration and raising questions about antral stem cell hierarchy.
Article
Biology
Julia E. Lefler, Catherine B. MarElia-Bennett, Katie A. Thies, Blake E. Hildreth, Sudarshana M. Sharma, Jason R. Pitarresi, Lu Han, Caroline Everett, Christopher Koivisto, Maria C. Cuitino, Cynthia Timmers, Elizabeth O'Quinn, Melodie Parrish, Martin J. Romeo, Amanda J. Linke, G. Aaron Hobbs, Gustavo Leone, Denis C. Guttridge, Teresa A. Zimmers, Gregory B. Lesinski, Michael C. Ostrowski
Summary: Disruption of the STAT3 signaling axis in stromal fibroblasts through genetic ablation of Stat3 slows tumor progression, increases survival, and reshapes the immune-suppressive tumor micro-environment in a PDAC mouse model. Loss of the tumor suppressor PTEN in pancreatic CAFs leads to increased STAT3 phosphorylation and promotes secretion of CXCL1.
LIFE SCIENCE ALLIANCE
(2022)
Article
Cell Biology
Toni T. Lemmetyinen, Emma W. Viitala, Linnea Wartiovaara, Tuomas Kaprio, Jaana Hagstrom, Caj Haglund, Pekka Katajisto, Timothy C. Wang, Eva Domenech-Moreno, Saara Ollila
Summary: Growth factors secreted by stromal fibroblasts, such as NRG1 and EREG, play a crucial role in regulating the intestinal epithelium. NRG1 promotes epithelial regeneration and protects against radiation-induced damage, while also suppressing the stem cell pool and remodeling the actin cytoskeleton. Interestingly, NRG1 does not support the growth of pre-tumorigenic intestinal organoids lacking the tumor suppressor Apc, suggesting a tumor-suppressive function.
DISEASE MODELS & MECHANISMS
(2023)
Article
Oncology
Jung Eun Baik, Li Li, Manish A. Shah, Daniel E. Freedberg, Zhezhen Jin, Timothy C. Wang, Yiping W. Han
Summary: Fusobacterium nucleatum (Fn) is a common gram-negative anaerobic bacterium that promotes colorectal cancer development through the secretion of FadAc. This study found that circulating levels of anti-FadAc IgA were significantly increased in patients with colorectal cancer, particularly in those with proximal tumors. Therefore, anti-FadAc IgA may serve as a serological biomarker for early detection of colorectal cancer.
CANCER RESEARCH COMMUNICATIONS
(2022)