检索结果-内蒙古大学图书馆

Yap reprograms glutamine metabolism to increase nucleotide biosynthesis and enable liver growth

NATURE CELL BIOLOGY 2016年第8期18卷 886-+页

作者： Cox, Andrew G. Hwang, Katie L. Brown, Kristin K. Evason, Kimberley J. Beltz, Sebastian Tsomides, Allison O'Connor, Keelin Galli, Giorgio G. Yimlamai, Dean Chhangawala, Sagar Yuan, Min Lien, Evan C. Wucherpfennig, Julia Nissim, Sahar Minami, Akihiro Cohen, David E. Camargo, Fernando D. Asara, John M. Houvras, Yariv Stainier, Didier Y. R. Goessling, Wolfram Harvard Med Sch Brigham & Womens Hosp Boston MA 02115 USA Harvard Med Sch Harvard MIT MD PhD Program Boston MA 02115 USA Harvard Med Sch Beth Israel Deaconess Med Ctr Boston MA 02115 USA Univ Utah Salt Lake City UT 84112 USA Harvard Med Sch Boston Childrens Hosp Boston MA 02115 USA Weill Cornell Med Coll New York NY 10065 USA Harvard Stem Cell Inst Cambridge MA 02138 USA Max Planck Inst D-61231 Bad Nauheim Germany Harvard Med Sch Dana Farber Canc Inst Boston MA 02115 USA Broad Inst MIT & Harvard Cambridge MA 02142 USA Novartis Inst BioMed Res Dis Area Oncol CH-4056 Basel Switzerland

The Hippo pathway is an important regulator of organ size and tumorigenesis. It is unclear, however, how Hippo signalling provides the cellular building blocks required for rapid growth. Here, we demonstrate that transgenic zebrafish expressing an activated form of the Hippo pathway effector Yap1 (also known as YAP) develop enlarged livers and are prone to liver tumour formation. Transcriptomic and metabolomic profiling identify that Yap1 reprograms glutamine metabolism. Yap1 directly enhances glutamine synthetase (glul) expression and activity, elevating steady-state levels of glutamine and enhancing the relative isotopic enrichment of nitrogen during de novo purine and pyrimidine biosynthesis. Genetic or pharmacological inhibition of GLUL diminishes the isotopic enrichment of nitrogen into nucleotides, suppressing hepatomegaly and the growth of liver cancer cells. Consequently, Yap-driven liver growth is susceptible to nucleotide inhibition. Together, our findings demonstrate that Yap1 integrates the anabolic demands of tissue growth during development and tumorigenesis by reprogramming nitrogen metabolism to stimulate nucleotide biosynthesis.

关键词： Cancer HIPPO signalling Metabolism Zebrafish

来源：评论

学校读者我要写书评

暂无评论

Annotations capturing cell type-specific TF binding explain a large fraction of disease heritability

引用

HUMAN MOLECULAR GENETICS 2020年第7期29卷 1057-1067页

作者： van de Geijn, Bryce Finucane, Hilary Gazal, Steven Hormozdiari, Farhad Amariuta, Tiffany Liu, Xuanyao Gusev, Alexander Loh, Po-Ru Reshef, Yakir Kichaev, Gleb Raychauduri, Soumya Price, Alkes L. Harvard TH Chan Sch Publ Hlth Dept Epidemiol 665 Huntington Ave Boston MA 02115 USA Harvard Med Sch Ctr Data Sci Boston MA 02215 USA Harvard Med Sch Brigham & Womens Hosp Dept Med Div Genet Boston MA 02215 USA Harvard Med Sch Brigham & Womens Hosp Dept Med Div Rheumatol Boston MA 02215 USA Harvard Med Sch Dept Biomed Informat Boston MA 02215 USA Harvard Univ Grad Sch Arts & Sci Boston MA 02215 USA Broad Inst MIT & Harvard Program Med & Populat Genet Cambridge MA 02142 USA Dana Farber Canc Inst Boston MA 02215 USA Brigham & Womens Hosp Boston MA 02215 USA Harvard Univ Dept Comp Sci Cambridge MA 02138 USA Harvard MIT MD PhD Program Boston MA 02215 USA Harvard TH Chan Sch Publ Hlth Dept Biostat Boston MA 02215 USA Univ Calif Los Angeles Bioinformat Interdept Program Los Angeles CA 90095 USA

Regulatory variation plays a major role in complex disease and that cell type-specific binding of transcription factors (TF) is critical to gene regulation. However, assessing the contribution of genetic variation in TF-binding sites to disease heritability is challenging, as binding is often cell type-specific and annotations from directly measured TF binding are not currently available for most cell type-TF pairs. We investigate approaches to annotate TF binding, including directly measured chromatin data and sequence-based predictions. We find that TF-binding annotations constructed by intersecting sequence-based TF-binding predictions with cell type-specific chromatin data explain a large fraction of heritability across a broad set of diseases and corresponding cell types;this strategy of constructing annotations addresses both the limitation that identical sequences may be bound or unbound depending on surrounding chromatin context and the limitation that sequence-based predictions are generally not cell type-specific. We partitioned the heritability of 49 diseases and complex traits using stratified linkage disequilibrium (LD) score regression with the baseline-LD model (which is not cell type-specific) plus the new annotations. We determined that 100 bp windows around MotifMap sequenced-based TF-binding predictions intersected with a union of six cell type-specific chromatin marks (imputed using Chromlmpute) performed best, with an 58% increase in heritability enrichment compared to the chromatin marks alone (11.6x vs. 7.3x, P = 9 x 10(-14) for difference) and a 20% increase in cell type-specific signal conditional on annotations from the baseline-LD model (P = 8 x 10(-11) for difference). Our results show that TF-binding annotations explain substantial disease heritability and can help refine genome-wide association signals.

关键词： chromatin gene expression regulation genome linkage disequilibrium genetics transcription factor imputation chromatin immunoprecipitation sequencing

来源：评论

学校读者我要写书评

暂无评论

Systemized approach to equipping medical students with naloxone: a student-driven initiative to combat the opioid crisis

引用

BMC MEDICAL EDUCATION 2024年第1期24卷 241页

作者： Saberi, Shahin A. Moore, Sydney Li, Sienna Mather, Rory Vu Daniels, Mary B. Shahani, Amrita Barreveld, Antje Griswold, Todd Mcguire, Patrick Connery, Hilary S. Harvard Med Sch Boston MA 02115 USA Harvard MIT MD PhD Program Boston MA 02115 USA Massachusetts Gen Hosp Dept Anesthesia Crit Care & Pain Med Boston MA 02114 USA MIT Program Hlth Sci & Technol Boston MA 02139 USA Brigham & Womens Hosp Outpatient Pharm Boston MA USA Newton Wellesley Hosp Dept Anesthesiol Newton MA USA Cambridge Hlth Alliance Ctr Mindfulness & Compass Cambridge MA USA Brigham & Womens Hosp Dept Psychiat Boston MA USA McLean Hosp Div Alcohol Drugs & Addict Belmont MA USA

BackgroundNaloxone is an effective and safe opioid reversal medication now approved by the U.S. Food and Drug Administration (FDA) for use with or without a prescription. Despite this, naloxone dissemination lags at a time when U.S. opioid-related mortality expands. The authors proposed distributing naloxone to all U.S. medical students using established statewide standing prescription orders for naloxone, eliminating the financial burden of over-the-counter costs on students and streamlining workflow for the pharmacy. By focusing naloxone distribution on medical students, we are able to capitalize on a group that is already primed on healthcare intervention, while also working to combat stigma in the emerging physician *** August 2022, the authors established a partnership between harvard Medical School (HMS) and the outpatient pharmacy at Brigham and Women's Hospital (BWH) to facilitate access to naloxone for HMS medical students. BWH developed a HIPAA-secure electronic form to collect individual prescription information. BWH pharmacists processed submissions daily, integrating the naloxone prescription requests into their workflow for in-person pick-up or mail-order delivery. The electronic form was disseminated to medical students through a required longitudinal addiction medicine curriculum, listserv messaging, and an extracurricular harm reduction *** the 2022-2023 academic year, 63 medical students obtained naloxone kits (two doses per kit) through this *** propose that medical schools advocate for a hospital pharmacy-initiated workflow focused on convenience and accessibility to expand naloxone access to medical students as a strategy to strengthen the U.S. emergency response and prevention efforts aimed at reducing opioid-related morbidity and mortality. Expansion of our program to BWH internal medicine residents increased our distribution to over 110 healthcare workers, and efforts to expand t

关键词： Naloxone Opioid overdose crisis Public health Opioid overdose prevention

来源：评论

学校读者我要写书评

暂无评论

CSmd1 regulates brain complement activity and circuit development

引用

BRAIN BEHAVIOR AND IMMUNITY 2024年 119卷 317-332页

作者： Baum, Matthew L. Wilton, Daniel K. Fox, Rachel G. Carey, Alanna Hsu, Yu-Han H. Hu, Ruilong Jantti, Henna J. Fahey, Jaclyn B. Muthukumar, Allie K. Salla, Nikkita Crotty, William Scott-Hewitt, Nicole Bien, Elizabeth Sabatini, David A. Lanser, Toby B. Frouin, Arnaud Gergits, Frederick Havik, Bjarte Gialeli, Chrysostomi Nacu, Eugene Lage, Kasper Blom, Anna M. Eggan, Kevin McCarroll, Steven A. Johnson, Matthew B. Stevens, Beth Harvard Med Sch Boston Childrens Hosp FM Kirby Neurobiol Ctr Dept Neurol Boston MA 02115 USA Harvard Med Sch Dept Genet Boston MA 02115 USA Broad Inst MIT & Harvard Stanley Ctr Psychiat Res Cambridge MA 02142 USA Harvard Med Sch MD PhD Program Harvard & MIT Boston MA 02115 USA Broad Inst MIT & Harvard Novo Nordisk Fdn Ctr Genom Mech Dis Cambridge MA 02142 USA Harvard Univ Dept Stem Cell & Regenerat Biol Cambridge MA 02138 USA Harvard Univ Harvard Stem Cell Inst Cambridge MA 02138 USA Sollien 147A N-5096 Bergen Norway Lund Univ Dept Translat Med Div Med Prot Chem S-21428 Malmo Sweden Lund Univ Dept Clin Sci Cardiovasc Res Translat Studies Res Grp S-21428 Malmo Sweden Howard Hughes Med Inst Chevy Chase MD 20815 USA Brigham & Womens Hosp Dept Psychiat Boston MA 02115 USA

Complement proteins facilitate synaptic elimination during neurodevelopmental pruning, but neural complement regulation is not well understood. CUB and Sushi Multiple Domains 1 (CSmd1) can regulate complement activity in vitro, is expressed in the brain, and is associated with increased schizophrenia risk. Beyond this, little is known about CSmd1 including whether it regulates complement activity in the brain or otherwise plays a role in neurodevelopment. We used biochemical, immunohistochemical, and proteomic techniques to examine the regional, cellular, and subcellular distribution as well as protein interactions of CSmd1 in the brain. To evaluate whether CSmd1 is involved in complement-mediated synapse elimination, we examined Csmd1-knockout mice and CSmd1-knockout human stem cell-derived neurons. We interrogated synapse and circuit development of the mouse visual thalamus, a process that involves complement pathway activity. We also quantified complement deposition on synapses in mouse visual thalamus and on cultured human neurons. Finally, we assessed uptake of synaptosomes by cultured microglia. We found that CSmd1 is present at synapses and interacts with complement proteins in the brain. Mice lacking Csmd1 displayed increased levels of complement component C3, an increased colocalization of C3 with presynaptic terminals, fewer retinogeniculate synapses, and aberrant segregation of eye-specific retinal inputs to the visual thalamus during the critical period of complement-dependent refinement of this circuit. Loss of CSmd1 in vivo enhanced synaptosome engulfment by microglia in vitro, and this effect was dependent on activity of the microglial complement receptor, CR3. Finally, human stem cell-derived neurons lacking CSmd1 were more vulnerable to complement deposition. These data suggest that CSmd1 can function as a regulator of complement-mediated synapse elimination in the brain during development.

关键词： Complement cascade Schizophrenia Synaptic pruning Complement control protein Neural circuits

来源：评论

学校读者我要写书评

暂无评论

Fate specification is spatially intermingled across planarian stem cells

引用

NATURE COMMUNICATIONS 2023年第1期14卷 7422页

作者： Park, Chanyoung Owusu-Boaitey, Kwadwo E. Valdes, Giselle M. Reddien, Peter W. Whitehead Inst Biomed Res Cambridge MA 02142 USA MIT Dept Biol Engn Cambridge MA 02139 USA Harvard Med Sch Harvard MIT MD PhD Program Boston MA USA Howard Hughes Med Inst Chevy Chase MD 20815 USA

Regeneration requires mechanisms for producing a wide array of cell types. Neoblasts are stem cells in the planarian Schmidtea mediterranea that undergo fate specification to produce over 125 adult cell types. Fate specification in neoblasts can be regulated through expression of fate-specific transcription factors. We utilize multiplexed error-robust fluorescence in situ hybridization (MERFISH) and whole-mount FISH to characterize fate choice distribution of stem cells within planarians. Fate choices are often made distant from target tissues and in a highly intermingled manner, with neighboring neoblasts frequently making divergent fate choices for tissues of different location and function. We propose that pattern formation is driven primarily by the migratory assortment of progenitors from mixed and spatially distributed fate-specified stem cells and that fate choice involves stem-cell intrinsic processes.

关键词：

来源：评论

学校读者我要写书评

暂无评论

Aging and neurodegeneration are associated with increased mutations in single human neurons

引用

SCIENCE 2018年第6375期359卷 555-558页

作者： Lodato, Michael A. Rodin, Rachel E. Bohrson, Craig L. Coulter, Michael E. Barton, Alison R. Kwon, Minseok Sherman, Maxwell A. Vitzthum, Carl M. Luquette, Lovelace J. Yandava, Chandri N. Yang, Pengwei Chittenden, Thomas W. Hatem, Nicole E. Ryu, Steven C. Woodworth, Mollie B. Park, Peter J. Walsh, Christopher A. Boston Childrens Hosp Manton Ctr Orphan Dis Div Genet & Genom Boston MA 02115 USA Boston Childrens Hosp Howard Hughes Med Inst Boston MA 02115 USA Harvard Med Sch Dept Neurol Boston MA 02115 USA Harvard Med Sch Dept Pediat Boston MA 02115 USA Broad Inst MIT & Harvard Cambridge MA 02142 USA Harvard Med Sch Program Neurosci Boston MA USA Harvard Med Sch Harvard MIT MD PHD Program Boston MA USA Harvard Med Sch Dept Biomed Informat Boston MA 02115 USA WuXi NextCODE Adv Artificial Intelligence Res Lab Computat Stat & Bioinformat Grp Cambridge MA USA MIT Dept Biol Engn 77 Massachusetts Ave Cambridge MA 02139 USA Harvard Med Sch Boston Childrens Hosp Div Genet & Genom Boston MA USA Brigham & Womens Hosp Div Genet 75 Francis St Boston MA 02115 USA Canada Coll Redwood City CA USA

It has long been hypothesized that aging and neurodegeneration are associated with somatic mutation in neurons;however, methodological hurdles have prevented testing this hypothesis directly. We used single-cell whole-genome sequencing to perform genome-wide somatic single-nucleotide variant (sSNV) identification on DNA from 161 single neurons from the prefrontal cortex and hippocampus of 15 normal individuals (aged 4 months to 82 years), as well as 9 individuals affected by early-onset neurodegeneration due to genetic disorders of DNA repair (Cockayne syndrome and xeroderma pigmentosum). sSNVs increased approximately linearly with age in both areas (with a higher rate in hippocampus) and were more abundant in neurodegenerative disease. The accumulation of somatic mutations with age-which we term genosenium-shows age-related, region-related, and disease-related molecular signatures and may be important in other human age-associated conditions.

关键词： AGING NEURODEGENERATION MUTATION (Biology) NEURONS CYTOSINE deaminase

来源：评论

学校读者我要写书评

暂无评论

Outflanking immunodominance to target subdominant broadly neutralizing epitopes

引用

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 2019年第27期116卷 13474-13479页

作者： Angeletti, Davide Kosik, Ivan Santos, Jefferson J. S. Yewdell, William T. Boudreau, Carolyn M. Mallajosyula, Vamsee V. A. Mankowski, Madeleine C. Chambers, Michael Prabhakaran, Madhu Hickman, Heather D. McDermott, Adrian B. Alter, Galit Chaudhuri, Jayanta Yewdell, Jonathan W. NIAID Lab Viral Dis NIH 9000 Rockville Pike Bethesda MD 20892 USA Univ Gothenburg Dept Microbiol & Immunol Inst Biomed S-40530 Gothenburg Sweden Mem Sloan Kettering Canc Ctr Immunol Program New York NY 10065 USA Ragon Inst MGH MIT & Harvard Univ Cambridge MA 02139 USA Harvard Univ Div Med Sci PhD Program Virol Boston MA 02115 USA Stanford Univ Inst Immun Transplantat & Infect Stanford CA 94305 USA NIAID Vaccine Res Ctr NIH 9000 Rockville Pike Bethesda MD 20892 USA NIAID Lab Clin Immunol & Microbiol NIH 9000 Rockville Pike Bethesda MD 20892 USA

A major obstacle to vaccination against antigenically variable viruses is skewing of antibody responses to variable immunodominant epitopes. For influenza virus hemagglutinin (HA), the immuno-dominance of the variable head impairs responses to the highly conserved stem. Here, we show that head immunodominance depends on the physical attachment of head to stem. Stem immuno-genicity is enhanced by immunizing with stem-only constructs or by increasing local HA concentration in the draining lymph node. Surprisingly, coimmunization of full-length HA and stem alters stem-antibody class switching. Our findings delineate strategies for overcoming immunodominance, with important implications for human vaccination.

关键词： influenza immunodominance B cell hemagglutinin antibodies

来源：评论

学校读者我要写书评

暂无评论

Massively multiplexed nucleic acid detection with Cas13

引用

NATURE 2020年第7811期582卷 277-+页

作者： Ackerman, Cheri M. Myhrvold, Cameron Thakku, Sri Gowtham Freije, Catherine A. Metsky, Hayden C. Yang, David K. Ye, Simon H. Boehm, Chloe K. Kosoko-Thoroddsen, Tinna-Solveig F. Kehe, Jared Nguyen, Tien G. Carter, Amber Kulesa, Anthony Barnes, John R. Dugan, Vivien G. Hung, Deborah T. Blainey, Paul C. Sabeti, Pardis C. Broad Inst MIT & Harvard Cambridge MA 02142 USA MIT Dept Biol Engn 77 Massachusetts Ave Cambridge MA 02139 USA Harvard Univ Dept Organism & Evolutionary Biol Cambridge MA 02138 USA Harvard Med Sch Div Hlth Sci & Technol Cambridge MA 02115 USA MIT 77 Massachusetts Ave Cambridge MA 02139 USA Harvard Med Sch PhD Program Virol Div Med Sci Boston MA 02115 USA MIT Dept Elect Engn & Comp Sci Cambridge MA 02139 USA Ctr Dis Control & Prevent Influenza Div Atlanta GA USA Massachusetts Gen Hosp Mol Biol Dept Boston MA 02114 USA Massachusetts Gen Hosp Ctr Computat & Integrat Biol Boston MA 02114 USA MIT Koch Inst Integrat Canc Res 77 Massachusetts Ave Cambridge MA 02139 USA Howard Hughes Med Inst Chevy Chase MD USA Harvard TH Chan Sch Publ Hearth Dept Immunol & Infect Dis Boston MA USA

The great majority of globally circulating pathogens go undetected, undermining patient care and hindering outbreak preparedness and response. To enable routine surveillance and comprehensive diagnostic applications, there is a need for detection technologies that can scale to test many samples(1-3)while simultaneously testing for many pathogens(4-6). Here, we develop Combinatorial Arrayed Reactions for Multiplexed Evaluation of Nucleic acids (CARMEN), a platform for scalable, multiplexed pathogen detection. In the CARMEN platform, nanolitre droplets containing CRISPR-based nucleic acid detection reagents(7)self-organize in a microwell array(8)to pair with droplets of amplified samples, testing each sample against each CRISPR RNA (crRNA) in replicate. The combination of CARMEN and Cas13 detection (CARMEN-Cas13) enables robust testing of more than 4,500 crRNA-target pairs on a single array. Using CARMEN-Cas13, we developed a multiplexed assay that simultaneously differentiates all 169 human-associated viruses with at least 10 published genome sequences and rapidly incorporated an additional crRNA to detect the causative agent of the 2020 COVID-19 pandemic. CARMEN-Cas13 further enables comprehensive subtyping of influenza A strains and multiplexed identification of dozens of HIV drug-resistance mutations. The intrinsic multiplexing and throughput capabilities of CARMEN make it practical to scale, as miniaturization decreases reagent cost per test by more than 300-fold. Scalable, highly multiplexed CRISPR-based nucleic acid detection shifts diagnostic and surveillance efforts from targeted testing of high-priority samples to comprehensive testing of large sample sets, greatly benefiting patients and public health(9-11).

关键词： Biological techniques Biotechnology Viral infection

来源：评论

学校读者我要写书评

暂无评论

Somatic genomic changes in single Alzheimer's disease neurons

引用

NATURE 2022年第7907期604卷 714-+页

作者： Miller, Michael B. Huang, August Yue Kim, Junho Zhou, Zinan Kirkham, Samantha L. Maury, Eduardo A. Ziegenfuss, Jennifer S. Reed, Hannah C. Neil, Jennifer E. Rento, Lariza Ryu, Steven C. Ma, Chanthia C. Luquette, Lovelace J. Ames, Heather M. Oakley, Derek H. Frosch, Matthew P. Hyman, Bradley T. Lodato, Michael A. Lee, Eunjung Alice Walsh, Christopher A. Brigham & Womens Hosp Harvard Med Sch Dept Pathol Div Neuropathol Boston MA USA Boston Childrens Hosp Manton Ctr Orphan Dis Div Genet & Genom Boston MA 02115 USA Broad Inst MIT & Harvard Cambridge MA 02142 USA Harvard Med Sch Dept Pediat Boston MA 02115 USA Sungkyunkwan Univ Dept Biol Sci Suwon South Korea Harvard Med Sch Harvard MIT MD PhD Program Bioinformat & Integrat Genom Program Boston MA USA Univ Massachusetts Dept Mol Cell & Canc Biol Chan Med Sch Worcester MA 01602 USA Allegheny Coll Meadville PA 16335 USA Howard Hughes Med Inst Boston MA 02115 USA Harvard Med Sch Dept Biomed Informat Boston MA USA Univ Maryland Sch Med Dept Pathol Baltimore MD 21201 USA Harvard Med Sch Massachusetts Gen Hosp Dept Pathol Boston MA USA Harvard Med Sch Massachusetts Gen Hosp Dept Neurol Boston MA USA Harvard Med Sch Dept Neurol Boston MA 02115 USA

Dementia in Alzheimer's disease progresses alongside neurodegeneration(1-4), but the specific events that cause neuronal dysfunction and death remain poorly understood. During normal ageing, neurons progressively accumulate somatic mutations(5) at rates similar to those of dividing cells(6,7) which suggests that genetic factors, environmental exposures or disease states might influence this accumulation(5). Here we analysed single-cell whole-genome sequencing data from 319 neurons from the prefrontal cortex and hippocampus of individuals with Alzheimer's disease and neurotypical control individuals. We found that somatic DNA alterations increase in individuals with Alzheimer's disease, with distinct molecular patterns. Normal neurons accumulate mutations primarily in an age-related pattern (signature A), which closely resembles 'clock-like' mutational signatures that have been previously described in healthy and cancerous cells(6-10). In neurons affected by Alzheimer's disease, additional DNA alterations are driven by distinct processes (signature C) that highlight C>A and other specific nucleotide changes. These changes potentially implicate nucleotide oxidation(4,11), which we show is increased in Alzheimer's-disease-affected neurons in situ. Expressed genes exhibit signature-specific damage, and mutations show a transcriptional strand bias, which suggests that transcription-coupled nucleotide excision repair has a role in the generation of mutations. The alterations in Alzheimer's disease affect coding exons and are predicted to create dysfunctional genetic knockout cells and proteostatic stress. Our results suggest that known pathogenic mechanisms in Alzheimer's disease may lead to genomic damage to neurons that can progressively impair function. The aberrant accumulation of DNA alterations in neurodegeneration provides insight into the cascade of molecular and cellular events that occurs in the development of Alzheimer's disease.

关键词： Alzheimer's disease DNA damage and repair Functional genomics Genomics Science Humanities and Social Sciences multidisciplinary

来源：评论

学校读者我要写书评

暂无评论

A transcription factor atlas of stem cell fate in planarians

引用

CELL REPORTS 2024年第3期43卷 113843页

作者： King, Hunter O. Owusu-Boaitey, Kwadwo E. Fincher, Christopher T. Reddien, Peter W. Howard Hughes Med Inst Chevy Chase MD 20815 USA Whitehead Inst Biomed Res Cambridge MA 02142 USA MIT Dept Biol Cambridge MA 02139 USA MIT Dept Brain & Cognit Sci Cambridge MA USA Harvard Med Sch Harvard MIT MD PhD Program Boston MA USA

Whole -body regeneration requires the ability to produce the full repertoire of adult cell types. The planarian Schmidtea mediterranea contains over 125 cell types, which can be regenerated from a stem cell population called neoblasts. Neoblast fate choice can be regulated by the expression of fate -specific transcription factors (FSTFs). How fate choices are made and distributed across neoblasts versus their post -mitotic progeny remains unclear. We used single -cell RNA sequencing to systematically map fate choices made in S/G2/M neoblasts and, separately, in their post -mitotic progeny that serve as progenitors for all adult cell types. We defined transcription factor expression signatures associated with all detected fates, identifying numerous new progenitor classes and FSTFs that regulate them. Our work generates an atlas of stem cell fates with associated transcription factor signatures for most cell types in a complete adult organism.

关键词： stem cells cell fate neoblasts planarians transcription factor regeneration progenitor

来源：评论

学校读者我要写书评

暂无评论

建议与咨询留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

时间限定

文献类型

馆藏选择

核心期刊

语言

文献类型

帮助

文字说明：

检索规则说明：

检索范例：

分类表

所选分类

限定检索结果

文献类型

馆藏范围

日期分布

学科分类号

主题

机构

作者

语言

请选择保存的检索档案：

请选择收藏分类：

通借通还

建议与咨询 留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

时间限定

文献类型

馆藏选择

核心期刊

语言

文献类型

帮助

文字说明：

检索规则说明：

检索范例：

分类表

所选分类

限定检索结果

文献类型

馆藏范围

日期分布

学科分类号

主题

机构

作者

语言

请选择保存的检索档案： 新增检索档案 确定 取消

请选择收藏分类： 新增自定义分类 确定 取消

通借通还

建议与咨询留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

请选择保存的检索档案：

请选择收藏分类：