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Chemoresistance in acute myeloid leukemia: An alternative single-cell RNA sequencing approach

Hematological oncology 2023年第3期41卷 499-509页

作者： Po-Liang Cheng Tzu-Hung Hsiao Chung-Hsing Chen Miao-Neng Hung Pei-Pei Jhan Li-Wen Lee Ting-Shuan Wu Jia-Rung Tsai Chieh-Lin Jerry Teng Department of Medical Research Taichung Veterans General Hospital Taichung Taiwan. Research Center for Biomedical Science and Engineering National Tsing Hua University Hsinchu Taiwan. Department of Public Health Fu Jen Catholic University New Taipei City Taiwan. Institute of Genomics and Bioinformatics National Chung Hsing University Taichung Taiwan. National Institute of Cancer Research National Health Research Institutes Zhunan Taiwan. Department of Post-Baccalaureate Medicine College of Medicine National Chung Hsing University Taichung Taiwan. Division of Hematology/Medical Oncology Department of Medicine Taichung Veterans General Hospital Taichung Taiwan. Department of Life Science Tunghai University Taichung Taiwan. School of Medicine Chung Shan Medical University Taichung Taiwan. Ph.D. Program in Translational Medicine National Chung Hsing University Taichung Taiwan. Rong Hsing Research Center for Translational Medicine National Chung Hsing University Taichung Taiwan.

Our previous study demonstrated that myc, mitochondrial oxidative phosphorylation, mTOR, and stemness are independently responsible for chemoresistance in acute myeloid leukemia (AML) cells. This study aimed to identify potential mechanisms of chemoresistance of the "7 + 3" induction in AML by using a single-cell RNA sequencing (scRNA-seq) approach. In the present study, 13 untreated patients with de novo AML were enrolled and stratified into two groups: complete remission (CR; n = 8) and non-CR (n = 5). Single-cell RNA sequencing was used to analyze genetic profiles of 28,950 AML cells from these patients; results were validated using a previously published bulk RNA-seq dataset. Our study results showed chemoresistant AML cells had premature accumulation during early hematopoiesis. Hematopoietic stem cell-like cells from the non-CR group expressed more leukemic stem cell markers (CD9, CD82, IL3RA, and IL1RAP) than those from the CR group. Chemoresistant progenitor cells had impaired myeloid differentiation owing to early arrest of hematopoiesis. Notably, AML cells analyzed by scRNA-seq and bulk RNA-seq harbored a comparable myeloid lineage cell fraction, which internally validated our results. Using the TCGA database, our analysis demonstrated that patients with AML with higher expression of chemoresistant genetic markers (IL3RA and IL1RAP) had a worse overall survival (p < 0.01 for IL3RA; p < 0.05 for IL1RAP). In conclusion, AML cells responsive and resistant to the "7 + 3" induction were derived from a diverse cancerous hematopoietic stem cell population, as indicated by the specific genetic biomarkers obtained using scRNA-seq approach. Furthermore, arrest of hematopoiesis was shown to occur earlier in chemoresistant AML cells, furthering the current understanding of chemoresistance in AML.

关键词： acute myeloid leukemia chemoresistance leukemia stem cells single-cell RNA-seq

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Data-Driven Two-Stage Framework for Identification and Characterization of Different Antibiotic-Resistant Escherichia coli Isolates Based on Mass Spectrometry Data

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Microbiology spectrum 2023年第3期11卷 e0347922页

作者： Chia-Ru Chung Hsin-Yao Wang Chun-Han Yao Li-Ching Wu Jang-Jih Lu Jorng-Tzong Horng Tzong-Yi Lee Department of Computer Science and Information Engineering National Central University Taoyuan Taiwan. Department of Laboratory Medicine Chang Gung Memorial Hospital at Linkou Taoyuan Taiwan. Ph.D. Program in Biomedical Engineering Chang Gung University Taoyuan Taiwan. Department of Biomedical Sciences and Engineering National Central University Taoyuan Taiwan. College of Medicine Chang Gung University Taoyuan Taiwan. Department of Medical Biotechnology and Laboratory Science Chang Gung University Taoyuan Taiwan. Department of Bioinformatics and Medical Engineering Asia University Taichung Taiwan. Institute of Bioinformatics and Systems Biology National Yang Ming Chiao Tung University Hsinchu Taiwan.

In clinical microbiology, matrix-assisted laser desorption ionization-time-of-flight mass spectrometry (MALDI-TOF MS) is frequently employed for rapid microbial identification. However, rapid identification of antimicrobial resistance (AMR) in Escherichia coli based on a large amount of MALDI-TOF MS data has not yet been reported. This may be because building a prediction model to cover all E. coli isolates would be challenging given the high diversity of the E. coli population. This study aimed to develop a MALDI-TOF MS-based, data-driven, two-stage framework for characterizing different AMRs in E. coli. Specifically, amoxicillin (AMC), ceftazidime (CAZ), ciprofloxacin (CIP), ceftriaxone (CRO), and cefuroxime (CXM) were used. In the first stage, we split the data into two groups based on informative peaks according to the importance of the random forest. In the second stage, prediction models were constructed using four different machine learning algorithms-logistic regression, support vector machine, random forest, and extreme gradient boosting (XGBoost). The findings demonstrate that XGBoost outperformed the other four machine learning models. The values of the area under the receiver operating characteristic curve were 0.62, 0.72, 0.87, 0.72, and 0.72 for AMC, CAZ, CIP, CRO, and CXM, respectively. This implies that a data-driven, two-stage framework could improve accuracy by approximately 2.8%. As a result, we developed AMR prediction models for E. coli using a data-driven two-stage framework, which is promising for assisting physicians in making decisions. Further, the analysis of informative peaks in future studies could potentially reveal new insights. Based on a large amount of matrix-assisted laser desorption ionization-time-of-flight mass spectrometry (MALDI-TOF MS) clinical data, comprising 37,918 Escherichia coli isolates, a data-driven two-stage framework was established to evaluate the antimicrobial resistance of E. coli. Five antibiotics, including a

关键词： MALDI-TOF MS antimicrobial resistance cephalosporin cephalosporins fluoroquinolones machine learning matrix-assisted laser desorption ionization–time of flight mass spectrometry penicillin penicillins

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Author Correction: SARS-CoV-2 infection engenders heterogeneous ribonucleoprotein interactions to impede translation elongation in the lungs

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EXPERIMENTAL AND MOLECULAR MEDICINE 2023年第12期55卷 2609-2609页

作者： Kim, Junsoo Youn, Daehwa Choi, Seunghoon Lee, Youn Woo Sumberzul, Dulguun Yoon, Jeongeun Lee, Hanju Bae, Jong Woo Noh, Hyuna On, Dain Hong, Seung-Min An, Se-Hee Jang, Hui Jeong Kim, Seo Yeon Kim, Young Been Hwang, Ji-Yeon Lee, Hyo-Jung Kim, Hong Bin Park, Jun Won Yun, Jun-Won Shin, Jeon-Soo Seo, Jun-Young Nam, Ki Taek Choi, Kang-Seuk Lee, Ho-Young Chang, Hyeshik Seong, Je Kyung Cho, Jun Center for RNA Research Institute for Basic Science (IBS) Seoul National University Seoul Republic of Korea Interdisciplinary Program in Bioinformatics Seoul National University Seoul Republic of Korea Department of Biomedical Science and Engineering Gwangju Institute of Science and Technology (GIST) Gwangju Republic of Korea Korea Mouse Phenotyping Center (KMPC) Seoul National University Seoul Republic of Korea Laboratory of Developmental Biology and Genomics Research Institute for Veterinary Science and BK 21 PLUS Program for Creative Veterinary Science Research College of Veterinary Medicine Seoul National University Seoul Republic of Korea Department of Nuclear Medicine Seoul National University Bundang Hospital Seongnam Republic of Korea School of Biological Sciences Seoul National University Seoul Republic of Korea Laboratory of Avian Diseases Research Institute for Veterinary Science and BK 21 PLUS Program for Creative Veterinary Science Research College of Veterinary Medicine Seoul National University Seoul Republic of Korea Preclinical Research Center Seoul National University Bundang Hospital Seongnam Republic of Korea Department of Periodontology Section of Dentistry Seoul National University Bundang Hospital Seongnam Republic of Korea Department of Internal Medicine Seoul National University Bundang Hospital Seoul National University College of Medicine Seongnam Republic of Korea Division of Biomedical Convergence College of Biomedical Science Kangwon National University ChunCheon Republic of Korea Laboratory of Veterinary Toxicology College of Veterinary Medicine Seoul National University Seoul Republic of Korea Severance Biomedical Science Institute Graduate School of Medical Science Brain Korea 21 Project Yonsei University College of Medicine Seoul Republic of Korea Department of Nuclear Medicine Seoul National University College of Medicine Seoul Republic of Korea Interdisciplinary Program and BIO MAX Institute Seoul National University

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Structural basis and synergism of ATP and Na⁺ activation in bacterial K⁺ uptake system KtrAB

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Nature Communications 2024年第1期15卷 3850页

作者： Chiang, Wesley Tien Chang, Yao-Kai Hui, Wei-Han Chang, Shu-Wei Liao, Chen-Yi Chang, Yi-Chuan Chen, Chun-Jung Wang, Wei-Chen Lai, Chien-Chen Wang, Chun-Hsiung Luo, Siou-Ying Huang, Ya-Ping Chou, Shan-Ho Horng, Tzyy-Leng Hou, Ming-Hon Muench, Stephen P. Chen, Ren-Shiang Tsai, Ming-Daw Hu, Nien-Jen Graduate Institute of Biochemistry National Chung Hsing University Taichung 402202 Taiwan Institute of Biological Chemistry Academia Sinica Taipei 115201 Taiwan Department of Civil Engineering National Taiwan University Taipei 106319 Taiwan Department of Biomedical Engineering National Taiwan University Taipei 10663 Taiwan Life Science Group Scientific Research Division National Synchrotron Radiation Research Center Hsinchu 30092 Taiwan Institute of Molecular Biology National Chung Hsing University Taichung 402202 Taiwan Graduate Institute of Chinese Medical Science China Medical University Taichung 406040 Taiwan Department of Applied Mathematics Feng Chia University Taichung 407102 Taiwan Institute of Genomics and Bioinformatics National Chung Hsing University Taichung 402202 Taiwan School of Biomedical Sciences Faculty of Biological Sciences and the Astbury Centre for Structural Molecular Biology University of Leeds Leeds LS2 9JT United Kingdom Department of Life Science Tunghai University Taichung 407224 Taiwan Institute of Biochemical Sciences National Taiwan University Taipei 106319 Taiwan Ph.D Program in Translational Medicine National Chung Hsing University Taichung 402202 Taiwan

The K+ uptake system KtrAB is essential for bacterial survival in low K+ environments. The activity of KtrAB is regulated by nucleotides and Na+. Previous studies proposed a putative gating mechanism of KtrB regulated...

The K⁺ uptake system KtrAB is essential for bacterial survival in low K⁺ environments. The activity of KtrAB is regulated by nucleotides and Na⁺. Previous studies proposed a putative gating mechanism of KtrB regulated by KtrA upon binding to ATP or ADP. However, how Na⁺ activates KtrAB and the Na⁺ binding site remain unknown. Here we present the cryo-EM structures of ATP- and ADP-bound KtrAB from Bacillus subtilis (BsKtrAB) both solved at 2.8 Å. A cryo-EM density at the intra-dimer interface of ATP-KtrA was identified as Na⁺, as supported by X-ray crystallography and ICP-MS. Thermostability assays and functional studies demonstrated that Na⁺ binding stabilizes the ATP-bound BsKtrAB complex and enhances its K⁺ flux activity. Comparing ATP- and ADP-BsKtrAB structures suggests that BsKtrB Arg417 and Phe91 serve as a channel gate. The synergism of ATP and Na⁺ in activating BsKtrAB is likely applicable to Na⁺-activated K⁺ channels in central nervous system. © The Author(s) 2024.

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Single-molecule localization microscopy reveals the ultrastructural constitution of distal appendages in expanded mammalian centrioles

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Nature communications 2023年第1期14卷 1688页

作者： Ting-Jui Ben Chang Jimmy Ching-Cheng Hsu T Tony Yang Department of Physics National Taiwan University Taipei Taiwan. Department of Electrical Engineering National Taiwan University Taipei Taiwan. Nano Science and Technology Program Taiwan International Graduate Program Academia Sinica and National Taiwan University Taipei Taiwan. Department of Electrical Engineering National Taiwan University Taipei Taiwan. tonyyang@ntu.edu.tw. Graduate Institute of Biomedical Electronics and Bioinformatics National Taiwan University Taipei Taiwan. tonyyang@ntu.edu.tw.

Distal appendages (DAPs) are vital in cilia formation, mediating vesicular and ciliary docking to the plasma membrane during early ciliogenesis. Although numerous DAP proteins arranging a nine-fold symmetry have been studied using superresolution microscopy analyses, the extensive ultrastructural understanding of the DAP structure developing from the centriole wall remains elusive owing to insufficient resolution. Here, we proposed a pragmatic imaging strategy for two-color single-molecule localization microscopy of expanded mammalian DAP. Importantly, our imaging workflow enables us to push the resolution limit of a light microscope well close to a molecular level, thus achieving an unprecedented mapping resolution inside intact cells. Upon this workflow, we unravel the ultra-resolved higher-order protein complexes of the DAP and its associated proteins. Intriguingly, our images show that C2CD3, microtubule triplet, MNR, CEP90, OFD1, and ODF2 jointly constitute a unique molecular configuration at the DAP base. Moreover, our finding suggests that ODF2 plays an auxiliary role in coordinating and maintaining DAP nine-fold symmetry. Together, we develop an organelle-based drift correction protocol and a two-color solution with minimum crosstalk, allowing a robust localization microscopy imaging of expanded DAP structures deep into the gel-specimen composites.

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Uncovering chromatin accessibility and cancer diagnostic potential via cell-free DNA utilization

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Science Bulletin 2024年第19期69卷 2987-2992页

作者： Jie Li Jiahui Chen Xin Sun Heli Yang Keyong Sun Chang Liu Yongwang Wang Mengyue Xu Xin Ji Ji Zhang Xiaojiang Wu Anqiang Wang Biao Fan Xiaolu Zhang Yue Wu Peilin Cui Junya Peng Yupei Zhao Wenming Wu Honghao Yu Zhaode Bu Jiafu Ji Xun Lan Department of Basic Medical Sciences School of MedicineTsinghua UniversityBeijing 100084China Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education/Beijing) Center of Gastrointestinal CancerPeking University Cancer Hospital&InstituteBeijing 100142China Guangxi Key Laboratory of Drug Discovery and Optimization Guilin Medical UniversityGuilin 541001China Department of General Surgery Peking Union Medical College HospitalPeking Union Medical CollegeBeijing 100730China Department of Internal Medicine International Medical Services(IMS)Beijing Tiantan Hospital of Capital Medical UniversityBeijing 100070China Institute of Clinical Medicine Peking Union Medical College HospitalChinese Academy of Medical Science and Peking Union Medical CollegeBeijing 100730China Academy of Biomedical Engineering Kunming Medical UniversityKunming 650500China MOE Key Laboratory of Bioinformatics Tsinghua UniversityBeijing 100084China Peking-Tsinghua-NIBS Joint Graduate Program Tsinghua UniversityBeijing 100084China Tsinghua-Peking Joint Center for Life Sciences Tsinghua UniversityBeijing 100084China Department of Anesthesiology Affiliated Hospital of Guilin Medical UniversityGuilin 541000China Key Laboratory of Medical Biotechnology and Translational Medicine Guilin Medical UniversityGuilin 541001China State Key Laboratory of Complex Severe and Rare Diseases Peking Union Medical College HospitalChinese Academy of Medical Science and Peking Union Medical CollegeBeijing 100730China Department of Gastric Surgery Zhejiang Cancer HospitalHangzhou Institute of Medicine(HIM)Chinese Academy of SciencesHangzhou 310022China The Islands Healthcare Complex-Macao Medical Center of Peking Union Medical College Hospital Macao 999078China

Gene expression patterns of tumor cells can be inferred from features of circulating cell-free DNA(cfDNA),such as histone modifications and fragmentation patterns at ***,the direct relationship between cfDNA patterns and tumor-specific chromatin accessibility has not yet been experimentally established,limiting its current application to cancer diagnosis alone.

关键词： diagnosis cancer alone

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Mechanistic insights into CLNS1A-mediated chemoresistance and tumor progression in non-small cell lung cancer

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Cancer Letters 2025年 626卷 217783页

作者： Wei, Tong-You Wade Hsia, Jiun-Yi Yang, Tsung-Ying Huang, Yu-Xu Wang, Guo-Zhi Liu, Yi-Chung Wang, Yi-Wun He, Fangzhou Chen, Jo-Mei Maureen Zhao, Guo-Jun Lyu, Ping-Chiang Su, Li-Jen Chiu, Shao-Chih Yu, Chang-Tze Ricky Department of Applied Chemistry National Chi Nan University Nantou Taiwan Division of Cardiology Department of Medicine University of California La Jolla San Diego CA United States Division of Thoracic Surgery Chung Shan Medical University Hospital Taichung Taiwan School of Medicine Chung Shan Medical University Taichung Taiwan Department of Chest Medicine Taichung Veterans General Hospital Taichung Taiwan Doctoral Program in Translational Medicine National Chung Hsing University Taichung Taiwan School of Basic Medicine JingGangShan University Ji'an China Institute of Population Sciences National Health Research Institutes Zhunan Taiwan Cardiovascular Research Center School of Basic Medical Sciences Xi'an Jiaotong University Health Science Center Xi'an China Department of Cardiology The First Affiliated Hospital of Zhengzhou University Zhengzhou China Institute of Bioinformatics and Structural Biology Department of Life Science National Tsing Hua University Hsinchu Taiwan Department of Biomedical Sciences and Engineering Education and Research Center for Technology Assisted Substance Abuse Prevention and Management and Core Facilities for High Throughput Experimental Analysis National Central University Taoyuan Taiwan Graduate Institute of Biomedical Sciences China Medical University Taichung Taiwan Translational Cell Therapy Center Department of Medical Research China Medical University Hospital Taichung Taiwan

CLNS1A is a chloride channel protein and an essential component of the methylosome complex, which additionally comprises PRMT5 and MEP50. In this study, we investigated its contribution to lung cancer and its potential as a therapeutic target. Analysis of transcriptomic datasets and western blotting revealed that CLNS1A, PRMT5, and MEP50 were overexpressed in lung cancer tissues, with elevated CLNS1A expression correlating with poor patient survival. CLNS1A overexpression enhanced platinum clearance from cells, increased the IC₅₀ values for chemotherapy, and improved cell survival. Conversely, the knockdown of CLNS1A increased drug accumulation, reduced survival, and increased sensitivity to chemotherapy. The 3W mutant, a chloride channel-defective variant with steric hindrance at key bottleneck residues, impaired chloride ion transport, thereby reducing drug resistance, migration, and anchorage-independent growth. Mechanistically, CLNS1A promotes drug efflux through its chloride channel activity and activates the FAK-SRC-RAC1 pathway to enhance motility and clonogenicity. It also facilitates PRMT5-mediated RUVBL1 methylation to support anti-apoptotic DNA damage response signaling. In vivo, CLNS1A overexpression accelerated tumor growth and reduced survival, whereas CLNS1A knockdown sensitized tumors to cisplatin, enhancing therapeutic efficacy. These findings suggest that CLNS1A is a potential biomarker and therapeutic target, and its inhibition offers a strategy to overcome drug resistance and limit the metastatic progression of lung cancer. © 2025 The Authors

关键词： Chemoresistance Chloride channel DNA damage response Lung cancer Metastasis

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Hydrogen sulfide coordinates glucose metabolism switch through destabilizing tetrameric pyruvate kinase M2

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Nature Communications 2024年第1期15卷 7463页

作者： Wang, Rong-Hsuan Chen, Pin-Ru Chen, Yue-Ting Chen, Yi-Chang Chu, Yu-Hsin Chien, Chia-Chen Chien, Po-Chen Lo, Shao-Yun Wang, Zhong-Liang Tsou, Min-Chen Chen, Ssu-Yu Chiu, Guang-Shen Chen, Wen-Ling Wu, Yi-Hsuan Wang, Lily Hui-Ching Wang, Wen-Ching Lin, Shu-Yi Kung, Hsing-Jien Wang, Lu-Hai Cheng, Hui-Chun Lin, Kai-Ti Institute of Biotechnology National Tsing Hua University Hsinchu Taiwan Institute of Bioinformatics and Structural Biology National Tsing Hua University Hsinchu Taiwan Institute of Molecular and Genomic Medicine National Health Research Institutes Zhunan Taiwan Institute of Molecular and Cellular Biology National Tsing Hua University Hsinchu Taiwan Department of Medical Science National Tsing Hua University Hsinchu Taiwan School of Medicine National Tsing Hua University Hsinchu Taiwan Department of Life Science National Tsing Hua University Hsinchu Taiwan Institute of Biomedical Engineering and Nanomedicine National Health Research Institutes Zhunan Taiwan College of Medical Science and Technology PhD Program for Cancer Biology and Drug Discovery Taipei Medical University Taipei Taiwan Chiese Medicine Research Center and Institute of Integrated Medicine China Medical University Taichung City Taiwan

Most cancer cells reprogram their glucose metabolic pathway from oxidative phosphorylation to aerobic glycolysis for energy production. By reducing enzyme activity of pyruvate kinase M2 (PKM2), cancer cells attain a greater fraction of glycolytic metabolites for macromolecule synthesis needed for rapid proliferation. Here we demonstrate that hydrogen sulfide (H₂S) destabilizes the PKM2 tetramer into monomer/dimer through sulfhydration at cysteines, notably at C326, leading to reduced PKM2 enzyme activity and increased PKM2-mediated transcriptional activation. Blocking PKM2 sulfhydration at C326 through amino acid mutation stabilizes the PKM2 tetramer and crystal structure further revealing the tetramer organization of PKM2-C326S. The PKM2-C326S mutant in cancer cells rewires glucose metabolism to mitochondrial respiration, significantly inhibiting tumor growth. In this work, we demonstrate that PKM2 sulfhydration by H₂S inactivates PKM2 activity to promote tumorigenesis and inhibiting this process could be a potential therapeutic approach for targeting cancer metabolism. © The Author(s) 2024.

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High Resolution Imaging of Virus in Liquid Droplets: The Application of Cryo-TEM Methodology to Improve Liquid-phase TEM Imaging of Biological Materials

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Microscopy and Microanalysis 2021年第S2期27卷 19-20页

作者： Madeline J. Dukes GM Jonaid William J. Dearnaley Michael A. Casasanta Deborah F. Kelly Protochips Inc.Morrisville NC USA. Bioinformatics and Genomics Graduate Program Huck Institutes of the Life Sciences Pennsylvania State University University Park PA USA. Department of Biomedical Engineering Pennsylvania State University University Park PA USA. Materials Research Institute Pennsylvania State University University Park PA USA. Center for Structural Oncology Pennsylvania State University University Park PA16802 USA.

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The cell surface marker CD36 selectively identifies matured,mitochondria-rich hPSC-cardiomyocytes

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细胞研究（英文版） 2020年第7期30卷 626-629页

作者： Ellen Ngar-Yun Poon Xiao-ling Luo Sarah E.Webb Bin Yan Rui Zhao Stanley Chun Ming Wu Yong Yang Peng Zhang Huajun Bai Jiaofang Shao Ching Man Chan Godfrey Chi-Fung Chan Suk Ying Tsang Rebekah L.Gundry Huang-Tian Yang Kenneth R.Boheler Department of Medicine and Therapeutics and Centre for Cardiovascular Genomics and Medicine The Chinese University of Hong Kong (CUHK) HKSAR China CAS Key Laboratory of Tissue Microenvironment and Tumor Laboratory of Molecular CardiologyShanghai Institute of Nutrition and Health University of Chinese Academy of Sciences (CAS) CAS Shanghai China Division of Life Science and State Key Laboratory of Molecular Neuroscience The Hong Kong University of Science and Technology HKSAR China Department of Computer Science The University of Hong Kong (HKU) HKSAR China Intervention and Cell Therapy Center Peking University Shenzhen Hospital Shenzhen China School of Life Sciences CUHK HKSAR China Department of Paediatrics and Adolescent Medicine HKU HKSAR China School of Biomedical Sciences HKU HKSAR China SUSTech Academy for Advanced Interdisciplinary Studies Southern University of Science and Technology (SUSTech) Shenzhen China Department of Bioinformatics School of Biomedical Engineering and InformaticsNanjing Medical University Nanjing Jiangsu China State Key Laboratory of Agrobiotechnology CUHK HKSAR China Department of Biochemistry and Center for Biomedical Mass Spectrometry Research Medical College of Wisconsin Milwaukee WIUSA CardiOmics Program Center for Heart and Vascular Research Division of Cardiovascular Medicine and Department of Cellular and Integrative Physiology University of Nebraska Medical Center Omaha NE USA Institute for Stem Cell and Regeneration Medicine CASBeijing China Division of Cardiology Department of Medicineand Department of Biomedical Engineering The Johns Hopkins University Baltimore MD USA

Dear Editor,Human pluripotent stem cell (hPSC)-derived cardiomyocytes (CMs) are of significant translational value to in vitro studies of human cardiac development, drug and cardiotoxicity testing and cardiac disease *** of hPSCs to CMs,however, yields mixed cultures of atrial-, ventricular-, and pacemaker-like cells as well as non-CMs in variable proportions.1

关键词： Stem-cell differentiation Stem cells

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