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Li X, Zhu G, Zhao B. Chromatin remodeling in tissue stem cell fate determination. CELL REGENERATION (LONDON, ENGLAND) 2024; 13:18. [PMID: 39348027 PMCID: PMC11442411 DOI: 10.1186/s13619-024-00203-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/19/2024] [Accepted: 09/22/2024] [Indexed: 10/01/2024]
Abstract
Tissue stem cells (TSCs), which reside in specialized tissues, constitute the major cell sources for tissue homeostasis and regeneration, and the contribution of transcriptional or epigenetic regulation of distinct biological processes in TSCs has been discussed in the past few decades. Meanwhile, ATP-dependent chromatin remodelers use the energy from ATP hydrolysis to remodel nucleosomes, thereby affecting chromatin dynamics and the regulation of gene expression programs in each cell type. However, the role of chromatin remodelers in tissue stem cell fate determination is less well understood. In this review, we systematically discuss recent advances in epigenetic control by chromatin remodelers of hematopoietic stem cells, intestinal epithelial stem cells, neural stem cells, and skin stem cells in their fate determination and highlight the importance of their essential role in tissue homeostasis, development, and regeneration. Moreover, the exploration of the molecular and cellular mechanisms of TSCs is crucial for advancing our understanding of tissue maintenance and for the discovery of novel therapeutic targets.
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Affiliation(s)
- Xinyang Li
- State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai, 200438, China
- Z Lab, bioGenous BIOTECH, Shanghai, 200438, China
| | - Gaoxiang Zhu
- School of Basic Medical Sciences, Jiangxi Medical College, The First Affiliated Hospital of Nanchang University, Nanchang University, Nanchang, 330031, China
| | - Bing Zhao
- School of Basic Medical Sciences, Jiangxi Medical College, The First Affiliated Hospital of Nanchang University, Nanchang University, Nanchang, 330031, China.
- Z Lab, bioGenous BIOTECH, Shanghai, 200438, China.
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Shi J, Wang Z, Wang Z, Shao G, Li X. Epigenetic regulation in adult neural stem cells. Front Cell Dev Biol 2024; 12:1331074. [PMID: 38357000 PMCID: PMC10864612 DOI: 10.3389/fcell.2024.1331074] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2023] [Accepted: 01/12/2024] [Indexed: 02/16/2024] Open
Abstract
Neural stem cells (NSCs) exhibit self-renewing and multipotential properties. Adult NSCs are located in two neurogenic regions of adult brain: the ventricular-subventricular zone (V-SVZ) of the lateral ventricle and the subgranular zone of the dentate gyrus in the hippocampus. Maintenance and differentiation of adult NSCs are regulated by both intrinsic and extrinsic signals that may be integrated through expression of some key factors in the adult NSCs. A number of transcription factors have been shown to play essential roles in transcriptional regulation of NSC cell fate transitions in the adult brain. Epigenetic regulators have also emerged as key players in regulation of NSCs, neural progenitor cells and their differentiated progeny via epigenetic modifications including DNA methylation, histone modifications, chromatin remodeling and RNA-mediated transcriptional regulation. This minireview is primarily focused on epigenetic regulations of adult NSCs during adult neurogenesis, in conjunction with transcriptional regulation in these processes.
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Affiliation(s)
- Jiajia Shi
- School of Life Science and Technology, ShanghaiTech University, Shanghai, China
| | - Zilin Wang
- School of Life Science and Technology, ShanghaiTech University, Shanghai, China
| | - Zhijun Wang
- Zhenhai Lianhua Hospital, Ningbo City, Zhejiang, China
| | - Guofeng Shao
- Department of Cardiothoracic Surgery, Lihuili Hospital Affiliated to Ningbo University, Ningbo City, Zhejiang, China
| | - Xiajun Li
- School of Life Science and Technology, ShanghaiTech University, Shanghai, China
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3
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Veschi V, Durinck K, Thiele CJ, Speleman F. Neuroblastoma Epigenetic Landscape: Drugging Opportunities. PEDIATRIC ONCOLOGY 2024:71-95. [DOI: 10.1007/978-3-031-51292-6_5] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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4
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Ke NY, Zhao TY, Wang WR, Qian YT, Liu C. Role of brahma-related gene 1/brahma-associated factor subunits in neural stem/progenitor cells and related neural developmental disorders. World J Stem Cells 2023; 15:235-247. [PMID: 37181007 PMCID: PMC10173807 DOI: 10.4252/wjsc.v15.i4.235] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/24/2022] [Revised: 02/12/2023] [Accepted: 03/20/2023] [Indexed: 04/26/2023] Open
Abstract
Different fates of neural stem/progenitor cells (NSPCs) and their progeny are determined by the gene regulatory network, where a chromatin-remodeling complex affects synergy with other regulators. Here, we review recent research progress indicating that the BRG1/BRM-associated factor (BAF) complex plays an important role in NSPCs during neural development and neural developmental disorders. Several studies based on animal models have shown that mutations in the BAF complex may cause abnormal neural differentiation, which can also lead to various diseases in humans. We discussed BAF complex subunits and their main characteristics in NSPCs. With advances in studies of human pluripotent stem cells and the feasibility of driving their differentiation into NSPCs, we can now investigate the role of the BAF complex in regulating the balance between self-renewal and differentiation of NSPCs. Considering recent progress in these research areas, we suggest that three approaches should be used in investigations in the near future. Sequencing of whole human exome and genome-wide association studies suggest that mutations in the subunits of the BAF complex are related to neurodevelopmental disorders. More insight into the mechanism of BAF complex regulation in NSPCs during neural cell fate decisions and neurodevelopment may help in exploiting new methods for clinical applications.
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Affiliation(s)
- Nai-Yu Ke
- The First Clinical Medical College, Anhui Medical University, Hefei 230032, Anhui Province, China
- Institute of Stem cells and Tissue Engineering, School of Basic Medical Sciences, Anhui Medical University, Hefei 230032, Anhui Province, China
| | - Tian-Yi Zhao
- Institute of Stem cells and Tissue Engineering, School of Basic Medical Sciences, Anhui Medical University, Hefei 230032, Anhui Province, China
| | - Wan-Rong Wang
- The First Clinical Medical College, Anhui Medical University, Hefei 230032, Anhui Province, China
- Institute of Stem cells and Tissue Engineering, School of Basic Medical Sciences, Anhui Medical University, Hefei 230032, Anhui Province, China
| | - Yu-Tong Qian
- The First Clinical Medical College, Anhui Medical University, Hefei 230032, Anhui Province, China
- Institute of Stem cells and Tissue Engineering, School of Basic Medical Sciences, Anhui Medical University, Hefei 230032, Anhui Province, China
| | - Chao Liu
- Institute of Stem cells and Tissue Engineering, School of Basic Medical Sciences, Anhui Medical University, Hefei 230032, Anhui Province, China
- Department of Histology and Embryology, School of Basic Medical Sciences, Anhui Medical University, Hefei 230032, Anhui Province, China.
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5
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Rowland ME, Jajarmi JM, Osborne TSM, Ciernia AV. Insights Into the Emerging Role of Baf53b in Autism Spectrum Disorder. Front Mol Neurosci 2022; 15:805158. [PMID: 35185468 PMCID: PMC8852769 DOI: 10.3389/fnmol.2022.805158] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2021] [Accepted: 01/11/2022] [Indexed: 12/15/2022] Open
Abstract
Accurate and precise regulation of gene expression is necessary to ensure proper brain development and plasticity across the lifespan. As an ATP-dependent chromatin-remodeling complex, the BAF (Brg1 Associated Factor) complex can alter histone-DNA interactions, facilitating dynamic changes in gene expression by controlling DNA accessibility to the transcriptional machinery. Mutations in 12 of the potential 29 subunit genes that compose the BAF nucleosome remodeling complex have been identified in several developmental disorders including Autism spectrum disorders (ASD) and intellectual disability. A novel, neuronal version of BAF (nBAF) has emerged as promising candidate in the development of ASD as its expression is tied to neuron differentiation and it’s hypothesized to coordinate expression of synaptic genes across brain development. Recently, mutations in BAF53B, one of the neuron specific subunits of the nBAF complex, have been identified in patients with ASD and Developmental and epileptic encephalopathy-76 (DEE76), indicating BAF53B is essential for proper brain development. Recent work in cultured neurons derived from patients with BAF53B mutations suggests links between loss of nBAF function and neuronal dendritic spine formation. Deletion of one or both copies of mouse Baf53b disrupts dendritic spine development, alters actin dynamics and results in fewer synapses in vitro. In the mouse, heterozygous loss of Baf53b severely impacts synaptic plasticity and long-term memory that is reversible with reintroduction of Baf53b or manipulations of the synaptic plasticity machinery. Furthermore, surviving Baf53b-null mice display ASD-related behaviors, including social impairments and repetitive behaviors. This review summarizes the emerging evidence linking deleterious variants of BAF53B identified in human neurodevelopmental disorders to abnormal transcriptional regulation that produces aberrant synapse development and behavior.
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Petrik D, Encinas JM. Perspective: Of Mice and Men - How Widespread Is Adult Neurogenesis? Front Neurosci 2019; 13:923. [PMID: 31555083 PMCID: PMC6727861 DOI: 10.3389/fnins.2019.00923] [Citation(s) in RCA: 20] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2019] [Accepted: 08/16/2019] [Indexed: 12/16/2022] Open
Abstract
These are exciting times for research on adult hippocampal neurogenesis (AHN). Debate and controversy regarding the existence of generation of new neurons in the adult, and even diseased human brain flourishes as articles against and in favor accumulate. Adult neurogenesis in the human brain is a phenomenon that does not share the qualities of quantum mechanics. The scientific community should agree that human AHN exists or does not, but not both at the same time. In this commentary, we discuss the latest research articles about hAHN and what their findings imply for the neurogenesis field.
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Affiliation(s)
- David Petrik
- School of Biosciences, Cardiff University, Cardiff, United Kingdom.,Institute of Stem Cell Research, Helmholtz Zentrum München, Munich, Germany.,Department of Physiological Genomics, Ludwig Maximilian University of Munich, Munich, Germany
| | - Juan M Encinas
- Laboratory of Neural Stem Cells and Neurogenesis, Achucarro Basque Center for Neuroscience, Leioa, Spain.,IKERBASQUE, The Basque Foundation for Science, Bilbao, Spain.,Department of Neurosciences, University of the Basque Country (UPV/EHU), Leioa, Spain
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7
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Alfert A, Moreno N, Kerl K. The BAF complex in development and disease. Epigenetics Chromatin 2019; 12:19. [PMID: 30898143 PMCID: PMC6427853 DOI: 10.1186/s13072-019-0264-y] [Citation(s) in RCA: 167] [Impact Index Per Article: 27.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2018] [Accepted: 03/13/2019] [Indexed: 01/16/2023] Open
Abstract
The ATP-dependent chromatin remodelling complex BAF (= mammalian SWI/SNF complex) is crucial for the regulation of gene expression and differentiation. In the course of evolution from yeast to mammals, the BAF complex evolved an immense complexity with a high number of subunits encoded by gene families. In this way, tissue-specific BAF function and regulation of development begin with the combinatorial assembly of distinct BAF complexes such as esBAF, npBAF and nBAF. Furthermore, whole-genome sequencing reveals the tremendous role BAF complex mutations have in both neurodevelopmental disorders and human malignancies. Therefore, gaining a more elaborate insight into how BAF complex assembly influences its function and which role distinct subunits play, will hopefully give rise to a better understanding of disease pathogenesis and ultimately to new treatments for many human diseases.
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Affiliation(s)
- Amelie Alfert
- Department of Paediatric Haematology and Oncology, University Children’s Hospital Muenster, Domagkstraße 24, 48149 Muenster, Germany
| | - Natalia Moreno
- Department of Paediatric Haematology and Oncology, University Children’s Hospital Muenster, Domagkstraße 24, 48149 Muenster, Germany
| | - Kornelius Kerl
- Department of Paediatric Haematology and Oncology, University Children’s Hospital Muenster, Domagkstraße 24, 48149 Muenster, Germany
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9
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Brown S, Matta A, Erwin M, Roberts S, Gruber HE, Hanley EN, Little CB, Melrose J. Cell Clusters Are Indicative of Stem Cell Activity in the Degenerate Intervertebral Disc: Can Their Properties Be Manipulated to Improve Intrinsic Repair of the Disc? Stem Cells Dev 2018; 27:147-165. [DOI: 10.1089/scd.2017.0213] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Affiliation(s)
- Sharon Brown
- Spinal Studies and ISTM (Keele University), Robert Jones and Agnes Hunt Orthopaedic Hospital, NHS Foundation Trust, Oswestry, United Kingdom
| | - Ajay Matta
- Krembil Research Institute, Toronto, Canada
| | - Mark Erwin
- Krembil Research Institute, Toronto, Canada
| | - Sally Roberts
- Spinal Studies and ISTM (Keele University), Robert Jones and Agnes Hunt Orthopaedic Hospital, NHS Foundation Trust, Oswestry, United Kingdom
| | - Helen E. Gruber
- Department of Orthopaedic Surgery, Carolinas Medical Center, Charlotte, North Carolina
| | - Edward N. Hanley
- Department of Orthopaedic Surgery, Carolinas Medical Center, Charlotte, North Carolina
| | - Christopher B. Little
- Raymond Purves Laboratory, Institute of Bone and Joint Research, Kolling Institute of Medical Research, The Royal North Shore Hospital, St. Leonards, NSW, Australia
- Sydney Medical School, Northern, The University of Sydney. Royal North Shore Hospital, St. Leonards, Australia
| | - James Melrose
- Raymond Purves Laboratory, Institute of Bone and Joint Research, Kolling Institute of Medical Research, The Royal North Shore Hospital, St. Leonards, NSW, Australia
- Sydney Medical School, Northern, The University of Sydney. Royal North Shore Hospital, St. Leonards, Australia
- Graduate School of Biomedical Engineering, University of New South Wales, Sydney, Australia
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10
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Sokpor G, Xie Y, Rosenbusch J, Tuoc T. Chromatin Remodeling BAF (SWI/SNF) Complexes in Neural Development and Disorders. Front Mol Neurosci 2017; 10:243. [PMID: 28824374 PMCID: PMC5540894 DOI: 10.3389/fnmol.2017.00243] [Citation(s) in RCA: 157] [Impact Index Per Article: 19.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2017] [Accepted: 07/18/2017] [Indexed: 12/26/2022] Open
Abstract
The ATP-dependent BRG1/BRM associated factor (BAF) chromatin remodeling complexes are crucial in regulating gene expression by controlling chromatin dynamics. Over the last decade, it has become increasingly clear that during neural development in mammals, distinct ontogenetic stage-specific BAF complexes derived from combinatorial assembly of their subunits are formed in neural progenitors and post-mitotic neural cells. Proper functioning of the BAF complexes plays critical roles in neural development, including the establishment and maintenance of neural fates and functionality. Indeed, recent human exome sequencing and genome-wide association studies have revealed that mutations in BAF complex subunits are linked to neurodevelopmental disorders such as Coffin-Siris syndrome, Nicolaides-Baraitser syndrome, Kleefstra's syndrome spectrum, Hirschsprung's disease, autism spectrum disorder, and schizophrenia. In this review, we focus on the latest insights into the functions of BAF complexes during neural development and the plausible mechanistic basis of how mutations in known BAF subunits are associated with certain neurodevelopmental disorders.
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Affiliation(s)
- Godwin Sokpor
- Institute of Neuroanatomy, University Medical Center, Georg-August-University GoettingenGoettingen, Germany
| | - Yuanbin Xie
- Institute of Neuroanatomy, University Medical Center, Georg-August-University GoettingenGoettingen, Germany
| | - Joachim Rosenbusch
- Institute of Neuroanatomy, University Medical Center, Georg-August-University GoettingenGoettingen, Germany
| | - Tran Tuoc
- Institute of Neuroanatomy, University Medical Center, Georg-August-University GoettingenGoettingen, Germany.,DFG Center for Nanoscale Microscopy and Molecular Physiology of the BrainGoettingen, Germany
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11
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Xiao C, Gao L, Hou Y, Xu C, Chang N, Wang F, Hu K, He A, Luo Y, Wang J, Peng J, Tang F, Zhu X, Xiong JW. Chromatin-remodelling factor Brg1 regulates myocardial proliferation and regeneration in zebrafish. Nat Commun 2016; 7:13787. [PMID: 27929112 PMCID: PMC5476829 DOI: 10.1038/ncomms13787] [Citation(s) in RCA: 63] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2016] [Accepted: 11/01/2016] [Indexed: 12/15/2022] Open
Abstract
The zebrafish possesses a remarkable capacity of adult heart regeneration, but the underlying mechanisms are not well understood. Here we report that chromatin remodelling factor Brg1 is essential for adult heart regeneration. Brg1 mRNA and protein are induced during heart regeneration. Transgenic over-expression of dominant-negative Xenopus Brg1 inhibits the formation of BrdU+/Mef2C+ and Tg(gata4:EGFP) cardiomyocytes, leading to severe cardiac fibrosis and compromised myocardial regeneration. RNA-seq and RNAscope analyses reveal that inhibition of Brg1 increases the expression of cyclin-dependent kinase inhibitors such as cdkn1a and cdkn1c in the myocardium after ventricular resection; and accordingly, myocardial-specific expression of dn-xBrg1 blunts myocardial proliferation and regeneration. Mechanistically, injury-induced Brg1, via its interaction with Dnmt3ab, suppresses the expression of cdkn1c by increasing the methylation level of CpG sites at the cdkn1c promoter. Taken together, our results suggest that Brg1 promotes heart regeneration by repressing cyclin-dependent kinase inhibitors partly through Dnmt3ab-dependent DNA methylation.
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Affiliation(s)
- Chenglu Xiao
- Institute of Molecular Medicine, Peking University, Beijing 100871, China.,Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Peking University, Beijing 100871, China.,State Key Laboratory of Natural and Biomimetic Drugs, Beijing 100871, China
| | - Lu Gao
- Institute of Molecular Medicine, Peking University, Beijing 100871, China.,Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Peking University, Beijing 100871, China.,State Key Laboratory of Natural and Biomimetic Drugs, Beijing 100871, China
| | - Yu Hou
- Biodynamic Optical Imaging Center, Peking University, Beijing 100871, China.,College of Life Sciences, Peking University, Beijing 100871, China
| | - Congfei Xu
- School of Life Sciences, University of Science and Technology of China, Hefei 230026, China.,Hefei National Laboratory for Physical Sciences at the Microscale, University of Science and Technology of China, Hefei 230026, China
| | - Nannan Chang
- Institute of Molecular Medicine, Peking University, Beijing 100871, China.,Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Peking University, Beijing 100871, China.,State Key Laboratory of Natural and Biomimetic Drugs, Beijing 100871, China
| | - Fang Wang
- Department of Biomedical Engineering, College of Engineering, Peking University, Beijing 100871, China
| | - Keping Hu
- Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences, Beijing 100193, China.,Peking Union Medical College, Beijing 100730, China
| | - Aibin He
- Institute of Molecular Medicine, Peking University, Beijing 100871, China.,Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Peking University, Beijing 100871, China
| | - Ying Luo
- Department of Biomedical Engineering, College of Engineering, Peking University, Beijing 100871, China
| | - Jun Wang
- School of Life Sciences, University of Science and Technology of China, Hefei 230026, China.,Hefei National Laboratory for Physical Sciences at the Microscale, University of Science and Technology of China, Hefei 230026, China
| | - Jinrong Peng
- College of Animal Sciences, Zhejiang University, Hangzhou 310058, China
| | - Fuchou Tang
- Biodynamic Optical Imaging Center, Peking University, Beijing 100871, China.,College of Life Sciences, Peking University, Beijing 100871, China
| | - Xiaojun Zhu
- Institute of Molecular Medicine, Peking University, Beijing 100871, China.,Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Peking University, Beijing 100871, China.,State Key Laboratory of Natural and Biomimetic Drugs, Beijing 100871, China
| | - Jing-Wei Xiong
- Institute of Molecular Medicine, Peking University, Beijing 100871, China.,Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Peking University, Beijing 100871, China.,State Key Laboratory of Natural and Biomimetic Drugs, Beijing 100871, China
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12
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Control of adult neurogenesis by programmed cell death in the mammalian brain. Mol Brain 2016; 9:43. [PMID: 27098178 PMCID: PMC4839132 DOI: 10.1186/s13041-016-0224-4] [Citation(s) in RCA: 91] [Impact Index Per Article: 10.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2016] [Accepted: 04/14/2016] [Indexed: 01/19/2023] Open
Abstract
The presence of neural stem cells (NSCs) and the production of new neurons in the adult brain have received great attention from scientists and the public because of implications to brain plasticity and their potential use for treating currently incurable brain diseases. Adult neurogenesis is controlled at multiple levels, including proliferation, differentiation, migration, and programmed cell death (PCD). Among these, PCD is the last and most prominent process for regulating the final number of mature neurons integrated into neural circuits. PCD can be classified into apoptosis, necrosis, and autophagic cell death and emerging evidence suggests that all three may be important modes of cell death in neural stem/progenitor cells. However, the molecular mechanisms that regulate PCD and thereby impact the intricate balance between self-renewal, proliferation, and differentiation during adult neurogenesis are not well understood. In this comprehensive review, we focus on the extent, mechanism, and biological significance of PCD for the control of adult neurogenesis in the mammalian brain. The role of intrinsic and extrinsic factors in the regulation of PCD at the molecular and systems levels is also discussed. Adult neurogenesis is a dynamic process, and the signals for differentiation, proliferation, and death of neural progenitor/stem cells are closely interrelated. A better understanding of how adult neurogenesis is influenced by PCD will help lead to important insights relevant to brain health and diseases.
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