A Contraction Stress Model of Hypertrophic Cardiomyopathy due to Sarcomere Mutations.


:Thick-filament sarcomere mutations are a common cause of hypertrophic cardiomyopathy (HCM), a disorder of heart muscle thickening associated with sudden cardiac death and heart failure, with unclear mechanisms. We engineered four isogenic induced pluripotent stem cell (iPSC) models of β-myosin heavy chain and myosin-binding protein C3 mutations, and studied iPSC-derived cardiomyocytes in cardiac microtissue assays that resemble cardiac architecture and biomechanics. All HCM mutations resulted in hypercontractility with prolonged relaxation kinetics in proportion to mutation pathogenicity, but not changes in calcium handling. RNA sequencing and expression studies of HCM models identified p53 activation, oxidative stress, and cytotoxicity induced by metabolic stress that can be reversed by p53 genetic ablation. Our findings implicate hypercontractility as a direct consequence of thick-filament mutations, irrespective of mutation localization, and the p53 pathway as a molecular marker of contraction stress and candidate therapeutic target for HCM patients.


Stem Cell Reports


Stem cell reports


Cohn R,Thakar K,Lowe A,Ladha FA,Pettinato AM,Romano R,Meredith E,Chen YS,Atamanuk K,Huey BD,Hinson JT




Has Abstract


2019-01-08 00:00:00












  • A method to identify and isolate pluripotent human stem cells and mouse epiblast stem cells using lipid body-associated retinyl ester fluorescence.

    abstract::We describe the use of a characteristic blue fluorescence to identify and isolate pluripotent human embryonic stem cells and human-induced pluripotent stem cells. The blue fluorescence emission (450-500 nm) is readily observed by fluorescence microscopy and correlates with the expression of pluripotency markers (OCT4,...

    journal_title:Stem cell reports

    pub_type: 杂志文章


    authors: Muthusamy T,Mukherjee O,Menon R,Megha PB,Panicker MM

    更新日期:2014-06-12 00:00:00

  • ADAM8 Is an Antigen of Tyrosine Kinase Inhibitor-Resistant Chronic Myeloid Leukemia Cells Identified by Patient-Derived Induced Pluripotent Stem Cells.

    abstract::Properties of cancer stem cells involved in drug resistance and relapse have significant effects on clinical outcome. Although tyrosine kinase inhibitors (TKIs) have dramatically improved survival of patients with chronic myeloid leukemia (CML), TKIs have not fully cured CML due to TKI-resistant CML stem cells. Moreov...

    journal_title:Stem cell reports

    pub_type: 杂志文章


    authors: Miyauchi M,Koya J,Arai S,Yamazaki S,Honda A,Kataoka K,Yoshimi A,Taoka K,Kumano K,Kurokawa M

    更新日期:2018-03-13 00:00:00

  • Efficient Generation of Small Intestinal Epithelial-like Cells from Human iPSCs for Drug Absorption and Metabolism Studies.

    abstract::The small intestine plays an important role in the absorption and metabolism of oral drugs. In the current evaluation system, it is difficult to predict the precise absorption and metabolism of oral drugs. In this study, we generated small intestinal epithelial-like cells from human induced pluripotent stem cells (hiP...

    journal_title:Stem cell reports

    pub_type: 杂志文章


    authors: Negoro R,Takayama K,Kawai K,Harada K,Sakurai F,Hirata K,Mizuguchi H

    更新日期:2018-12-11 00:00:00

  • Functional Properties of Engineered Heart Slices Incorporating Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes.

    abstract::Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) hold great promise for cardiac studies, but their structural and functional immaturity precludes their use as faithful models of adult myocardium. Here we describe engineered heart slices (EHS), preparations of decellularized porcine myocardium rep...

    journal_title:Stem cell reports

    pub_type: 杂志文章


    authors: Blazeski A,Lowenthal J,Zhu R,Ewoldt J,Boheler KR,Tung L

    更新日期:2019-05-14 00:00:00

  • LIN28B Impairs the Transition of hESC-Derived β Cells from the Juvenile to Adult State.

    abstract::Differentiation of human embryonic stem cells into pancreatic β cells holds great promise for the treatment of diabetes. Recent advances have led to the production of glucose-responsive insulin-secreting cells in vitro, but resulting cells remain less mature than their adult primary β cell counterparts. The barrier(s)...

    journal_title:Stem cell reports

    pub_type: 杂志文章


    authors: Zhou X,Nair GG,Russ HA,Belair CD,Li ML,Shveygert M,Hebrok M,Blelloch R

    更新日期:2020-01-14 00:00:00

  • Craniometaphyseal Dysplasia Mutations in ANKH Negatively Affect Human Induced Pluripotent Stem Cell Differentiation into Osteoclasts.

    abstract::We identified osteoclast defects in craniometaphyseal dysplasia (CMD) using an easy-to-use protocol for differentiating osteoclasts from human induced pluripotent stem cells (hiPSCs). CMD is a rare genetic bone disorder, characterized by life-long progressive thickening of craniofacial bones and abnormal shape of long...

    journal_title:Stem cell reports

    pub_type: 杂志文章


    authors: Chen IP,Luxmi R,Kanaujiya J,Hao Z,Reichenberger EJ

    更新日期:2017-11-14 00:00:00

  • Targeted Repair of p47-CGD in iPSCs by CRISPR/Cas9: Functional Correction without Cleavage in the Highly Homologous Pseudogenes.

    abstract::Mutations in the NADPH oxidase, which is crucial for the respiratory burst in phagocytes, result in chronic granulomatous disease (CGD). The only curative treatment option for CGD patients, who suffer from severe infections, is allogeneic bone marrow transplantation. Over 90% of patients with mutations in the p47phox ...

    journal_title:Stem cell reports

    pub_type: 杂志文章


    authors: Klatt D,Cheng E,Philipp F,Selich A,Dahlke J,Schmidt RE,Schott JW,Büning H,Hoffmann D,Thrasher AJ,Schambach A

    更新日期:2019-10-08 00:00:00

  • A Cdx4-Sall4 regulatory module controls the transition from mesoderm formation to embryonic hematopoiesis.

    abstract::Deletion of caudal/cdx genes alters hox gene expression and causes defects in posterior tissues and hematopoiesis. Yet, the defects in hox gene expression only partially explain these phenotypes. To gain deeper insight into Cdx4 function, we performed chromatin immunoprecipitation sequencing (ChIP-seq) combined with g...

    journal_title:Stem cell reports

    pub_type: 杂志文章


    authors: Paik EJ,Mahony S,White RM,Price EN,Dibiase A,Dorjsuren B,Mosimann C,Davidson AJ,Gifford D,Zon LI

    更新日期:2013-11-07 00:00:00

  • Studies in an Early Development Window Unveils a Severe HSC Defect in both Murine and Human Fanconi Anemia.

    abstract::Fanconi anemia (FA) causes bone marrow failure early during childhood, and recent studies indicate that a hematopoietic defect could begin in utero. We performed a unique kinetics study of hematopoiesis in Fancg-/- mouse embryos, between the early embryonic day 11.5 (E11.5) to E12.5 developmental window (when the high...

    journal_title:Stem cell reports

    pub_type: 杂志文章


    authors: Domenech C,Maillard L,Rousseau A,Guidez F,Petit L,Pla M,Clay D,Guimiot F,Sanfilippo S,Jacques S,de la Grange P,Robil N,Soulier J,Souyri M

    更新日期:2018-11-13 00:00:00

  • Direct reprogramming of human fibroblasts toward a cardiomyocyte-like state.

    abstract::Direct reprogramming of adult somatic cells into alternative cell types has been shown for several lineages. We previously showed that GATA4, MEF2C, and TBX5 (GMT) directly reprogrammed nonmyocyte mouse heart cells into induced cardiomyocyte-like cells (iCMs) in vitro and in vivo. However, GMT alone appears insufficie...

    journal_title:Stem cell reports

    pub_type: 杂志文章


    authors: Fu JD,Stone NR,Liu L,Spencer CI,Qian L,Hayashi Y,Delgado-Olguin P,Ding S,Bruneau BG,Srivastava D

    更新日期:2013-08-22 00:00:00

  • Intercellular Adhesion-Dependent Cell Survival and ROCK-Regulated Actomyosin-Driven Forces Mediate Self-Formation of a Retinal Organoid.

    abstract::In this study we dissected retinal organoid morphogenesis in human embryonic stem cell (hESC)-derived cultures and established a convenient method for isolating large quantities of retinal organoids for modeling human retinal development and disease. Epithelialized cysts were generated via floating culture of clumps o...

    journal_title:Stem cell reports

    pub_type: 杂志文章


    authors: Lowe A,Harris R,Bhansali P,Cvekl A,Liu W

    更新日期:2016-05-10 00:00:00

  • Integrated Genomic Analysis of Diverse Induced Pluripotent Stem Cells from the Progenitor Cell Biology Consortium.

    abstract::The rigorous characterization of distinct induced pluripotent stem cells (iPSC) derived from multiple reprogramming technologies, somatic sources, and donors is required to understand potential sources of variability and downstream potential. To achieve this goal, the Progenitor Cell Biology Consortium performed compr...

    journal_title:Stem cell reports

    pub_type: 杂志文章


    authors: Salomonis N,Dexheimer PJ,Omberg L,Schroll R,Bush S,Huo J,Schriml L,Ho Sui S,Keddache M,Mayhew C,Shanmukhappa SK,Wells J,Daily K,Hubler S,Wang Y,Zambidis E,Margolin A,Hide W,Hatzopoulos AK,Malik P,Cancelas JA,Aro

    更新日期:2016-07-12 00:00:00

  • Rapid cellular phenotyping of human pluripotent stem cell-derived cardiomyocytes using a genetically encoded fluorescent voltage sensor.

    abstract::In addition to their promise in regenerative medicine, pluripotent stem cells have proved to be faithful models of many human diseases. In particular, patient-specific stem cell-derived cardiomyocytes recapitulate key features of several life-threatening cardiac arrhythmia syndromes. For both modeling and regenerative...

    journal_title:Stem cell reports

    pub_type: 杂志文章


    authors: Leyton-Mange JS,Mills RW,Macri VS,Jang MY,Butte FN,Ellinor PT,Milan DJ

    更新日期:2014-02-06 00:00:00

  • GATA6-AS1 Regulates GATA6 Expression to Modulate Human Endoderm Differentiation.

    abstract::Transcriptome analysis has uncovered a series of long noncoding RNAs (lncRNAs) transcribed during cell differentiation, but how lncRNA is integrated with known transcriptional regulatory network is poorly understood. Here, we utilize human definitive endoderm differentiation as a model system and decipher the function...

    journal_title:Stem cell reports

    pub_type: 杂志文章


    authors: Yang J,Lu P,Li M,Yan C,Zhang T,Jiang W

    更新日期:2020-09-08 00:00:00

  • Characterizing Direct-to-Consumer Stem Cell Businesses in the Southwest United States.

    abstract::There are currently hundreds of businesses across the United States offering direct-to-consumer stem cell treatments that have not been through regulatory approval by the Food and Drug Administration (FDA). Here, we provide a detailed characterization of nearly 170 stem cell businesses operating in the Southwest Unite...

    journal_title:Stem cell reports

    pub_type: 杂志文章


    authors: Frow EK,Brafman DA,Muldoon A,Krum L,Williams P,Becker B,Nelson JP,Pritchett A

    更新日期:2019-08-13 00:00:00

  • FAM122A Inhibits Erythroid Differentiation through GATA1.

    abstract::FAM122A is a highly conserved housekeeping gene, but its physiological and pathophysiological roles remain greatly elusive. Based on the fact that FAM122A is highly expressed in human CD71+ early erythroid cells, herein we report that FAM122A is downregulated during erythroid differentiation, while its overexpression ...

    journal_title:Stem cell reports

    pub_type: 杂志文章


    authors: Chen J,Zhou Q,Liu MH,Yang YS,Wang YQ,Huang Y,Chen GQ

    更新日期:2020-09-08 00:00:00

  • Identifying division symmetry of mouse embryonic stem cells: negative impact of DNA methyltransferases on symmetric self-renewal.

    abstract::Cell division is a process by which a mother cell divides into genetically identical sister cells, although sister cells often display considerable diversity. In this report, over 350 sister embryonic stem cells (ESCs) were isolated through a microdissection method, and then expression levels of 48 key genes were exam...

    journal_title:Stem cell reports

    pub_type: 杂志文章


    authors: Jasnos L,Aksoy FB,Hersi HM,Wantuch S,Sawado T

    更新日期:2013-09-26 00:00:00

  • Microglia-Secreted Factors Enhance Dopaminergic Differentiation of Tissue- and iPSC-Derived Human Neural Stem Cells.

    abstract::Microglia have recently been established as key regulators of brain development. However, their role in neuronal subtype specification remains largely unknown. Using three different co-culture setups, we show that microglia-secreted factors enhance dopaminergic differentiation of somatic and induced pluripotent stem c...

    journal_title:Stem cell reports

    pub_type: 杂志文章


    authors: Schmidt SI,Bogetofte H,Ritter L,Agergaard JB,Hammerich D,Kabiljagic AA,Wlodarczyk A,Lopez SG,Sørensen MD,Jørgensen ML,Okarmus J,Serrano AM,Kristensen BW,Freude K,Owens T,Meyer M

    更新日期:2021-01-06 00:00:00

  • In Vitro Propagation and Branching Morphogenesis from Single Ureteric Bud Cells.

    abstract::A method to maintain and rebuild ureteric bud (UB)-like structures from UB cells in vitro could provide a useful tool for kidney regeneration. We aimed in our present study to establish a serum-free culture system that enables the expansion of UB progenitor cells, i.e., UB tip cells, and reconstruction of UB-like stru...

    journal_title:Stem cell reports

    pub_type: 杂志文章


    authors: Yuri S,Nishikawa M,Yanagawa N,Jo OD,Yanagawa N

    更新日期:2017-02-14 00:00:00

  • Development and Dynamic Regulation of Mitochondrial Network in Human Midbrain Dopaminergic Neurons Differentiated from iPSCs.

    abstract::Mitochondria are critical to neurogenesis, but the mechanisms of mitochondria in neurogenesis have not been well explored. We fully characterized mitochondrial alterations and function in relation to the development of human induced pluripotent stem cell (hiPSC)-derived dopaminergic (DA) neurons. Following directed di...

    journal_title:Stem cell reports

    pub_type: 杂志文章


    authors: Fang D,Qing Y,Yan S,Chen D,Yan SS

    更新日期:2016-10-11 00:00:00

  • Exercise-Induced Activated Platelets Increase Adult Hippocampal Precursor Proliferation and Promote Neuronal Differentiation.

    abstract::Physical activity is a strong positive physiological modulator of adult neurogenesis in the hippocampal dentate gyrus. Although the underlying regulatory mechanisms are still unknown, systemic processes must be involved. Here we show that platelets are activated after acute periods of running, and that activated plate...

    journal_title:Stem cell reports

    pub_type: 杂志文章


    authors: Leiter O,Seidemann S,Overall RW,Ramasz B,Rund N,Schallenberg S,Grinenko T,Wielockx B,Kempermann G,Walker TL

    更新日期:2019-04-09 00:00:00

  • The Periostin/Integrin-αv Axis Regulates the Size of Hematopoietic Stem Cell Pool in the Fetal Liver.

    abstract::We earlier showed that outside-in integrin signaling through POSTN-ITGAV interaction plays an important role in regulating adult hematopoietic stem cell (HSC) quiescence. Here, we show that Itgav deletion results in increased frequency of phenotypic HSCs in fetal liver (FL) due to faster proliferation. Systemic deleti...

    journal_title:Stem cell reports

    pub_type: 杂志文章


    authors: Biswas A,Roy IM,Babu PC,Manesia J,Schouteden S,Vijayakurup V,Anto RJ,Huelsken J,Lacy-Hulbert A,Verfaillie CM,Khurana S

    更新日期:2020-08-11 00:00:00

  • Sox100B Regulates Progenitor-Specific Gene Expression and Cell Differentiation in the Adult Drosophila Intestine.

    abstract::Robust production of terminally differentiated cells from self-renewing resident stem cells is essential to maintain proper tissue architecture and physiological functions, especially in high-turnover tissues. However, the transcriptional networks that precisely regulate cell transition and differentiation are poorly ...

    journal_title:Stem cell reports

    pub_type: 杂志文章


    authors: Meng FW,Rojas Villa SE,Biteau B

    更新日期:2020-02-11 00:00:00

  • Identification and Characterization of the Dermal Panniculus Carnosus Muscle Stem Cells.

    abstract::The dermal Panniculus carnosus (PC) muscle is important for wound contraction in lower mammals and represents an interesting model of muscle regeneration due to its high cell turnover. The resident satellite cells (the bona fide muscle stem cells) remain poorly characterized. Here we analyzed PC satellite cells with r...

    journal_title:Stem cell reports

    pub_type: 杂志文章


    authors: Naldaiz-Gastesi N,Goicoechea M,Alonso-Martín S,Aiastui A,López-Mayorga M,García-Belda P,Lacalle J,San José C,Araúzo-Bravo MJ,Trouilh L,Anton-Leberre V,Herrero D,Matheu A,Bernad A,García-Verdugo JM,Carvajal JJ,Relaix F,L

    更新日期:2016-09-13 00:00:00

  • Pathological ASXL1 Mutations and Protein Variants Impair Neural Crest Development.

    abstract::The neural crest (NC) gives rise to a multitude of fetal tissues, and its misregulation is implicated in congenital malformations. Here, we investigated molecular mechanisms pertaining to NC-related symptoms in Bohring-Opitz syndrome (BOS), a developmental disorder linked to mutations in the Polycomb group factor Addi...

    journal_title:Stem cell reports

    pub_type: 杂志文章


    authors: Matheus F,Rusha E,Rehimi R,Molitor L,Pertek A,Modic M,Feederle R,Flatley A,Kremmer E,Geerlof A,Rishko V,Rada-Iglesias A,Drukker M

    更新日期:2019-05-14 00:00:00

  • Stabilizing the Retromer Complex in a Human Stem Cell Model of Alzheimer's Disease Reduces TAU Phosphorylation Independently of Amyloid Precursor Protein.

    abstract::Developing effective therapeutics for complex diseases such as late-onset, sporadic Alzheimer's disease (SAD) is difficult due to genetic and environmental heterogeneity in the human population and the limitations of existing animal models. Here, we used hiPSC-derived neurons to test a compound that stabilizes the ret...

    journal_title:Stem cell reports

    pub_type: 杂志文章


    authors: Young JE,Fong LK,Frankowski H,Petsko GA,Small SA,Goldstein LSB

    更新日期:2018-03-13 00:00:00

  • Let Me Speak! A Reviewers' Guide to Writing a Successful Meeting Abstract.

    abstract::Being able to summarize properly your work is not an easy task. But learning the skill of writing a good abstract is very important, as it can open many doors, including the possibility to be selected as a speaker at conferences. As meeting abstract reviewers, here we are writing to give you insights into the abstract...

    journal_title:Stem cell reports

    pub_type: 杂志文章


    authors: Sturgeon CM,Ditadi A

    更新日期:2018-12-11 00:00:00

  • Blockage of the Epithelial-to-Mesenchymal Transition Is Required for Embryonic Stem Cell Derivation.

    abstract::Pluripotent cells emanate from the inner cell mass (ICM) of the blastocyst and when cultivated under optimal conditions immortalize as embryonic stem cells (ESCs). The fundamental mechanism underlying ESC derivation has, however, remained elusive. Recently, we have devised a highly efficient approach for establishing ...

    journal_title:Stem cell reports

    pub_type: 杂志文章


    authors: Totonchi M,Hassani SN,Sharifi-Zarchi A,Tapia N,Adachi K,Arand J,Greber B,Sabour D,Araúzo-Bravo MJ,Walter J,Pakzad M,Gourabi H,Schöler HR,Baharvand H

    更新日期:2017-10-10 00:00:00

  • Histone H3 Lysine 9 Acetylation Obstructs ATM Activation and Promotes Ionizing Radiation Sensitivity in Normal Stem Cells.

    abstract::Dynamic spatiotemporal modification of chromatin around DNA damage is vital for efficient DNA repair. Normal stem cells exhibit an attenuated DNA damage response (DDR), inefficient DNA repair, and high radiosensitivity. The impact of unique chromatin characteristics of stem cells in DDR regulation is not yet recognize...

    journal_title:Stem cell reports

    pub_type: 杂志文章


    authors: Meyer B,Fabbrizi MR,Raj S,Zobel CL,Hallahan DE,Sharma GG

    更新日期:2016-12-13 00:00:00

  • Human iPSC-Derived Endothelial Cells and Microengineered Organ-Chip Enhance Neuronal Development.

    abstract::Human stem cell-derived models of development and neurodegenerative diseases are challenged by cellular immaturity in vitro. Microengineered organ-on-chip (or Organ-Chip) systems are designed to emulate microvolume cytoarchitecture and enable co-culture of distinct cell types. Brain microvascular endothelial cells (BM...

    journal_title:Stem cell reports

    pub_type: 杂志文章


    authors: Sances S,Ho R,Vatine G,West D,Laperle A,Meyer A,Godoy M,Kay PS,Mandefro B,Hatata S,Hinojosa C,Wen N,Sareen D,Hamilton GA,Svendsen CN

    更新日期:2018-04-10 00:00:00