Embryonic Heart Progenitors and Cardiogenesis

Brade, Thomas; Pane, Luna Simona; Moretti, Alessandra; Chien, Kenneth R.; Laugwitz, Karl‐Ludwig

doi:10.1101/cshperspect.a013847

Cited by 204 publications

(227 citation statements)

References 108 publications

(101 reference statements)

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“…S1). Extensive prior knowledge guided us to identify (i) intermediate cell states at branch points of development, (ii) key transcriptional regulators that control cell fate decisions, and (iii) instructive signals that guide the differentiation process (2,(13)(14)(15)(16)(17). We used this knowledge to select 96 gene markers for our study (Dataset S1, Table S1).…”

Section: Resultsmentioning

confidence: 99%

Cell population structure prior to bifurcation predicts efficiency of directed differentiation in human induced pluripotent cells

Bargaje

Trachana

Shelton

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

118

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Steering the differentiation of induced pluripotent stem cells (iPSCs) toward specific cell types is crucial for patient-specific disease modeling and drug testing. This effort requires the capacity to predict and control when and how multipotent progenitor cells commit to the desired cell fate. Cell fate commitment represents a critical state transition or "tipping point" at which complex systems undergo a sudden qualitative shift. To characterize such transitions during iPSC to cardiomyocyte differentiation, we analyzed the gene expression patterns of 96 developmental genes at single-cell resolution. We identified a bifurcation event early in the trajectory when a primitive streak-like cell population segregated into the mesodermal and endodermal lineages. Before this branching point, we could detect the signature of an imminent critical transition: increase in cell heterogeneity and coordination of gene expression. Correlation analysis of gene expression profiles at the tipping point indicates transcription factors that drive the state transition toward each alternative cell fate and their relationships with specific phenotypic readouts. The latter helps us to facilitate small molecule screening for differentiation efficiency. To this end, we set up an analysis of cell population structure at the tipping point after systematic variation of the protocol to bias the differentiation toward mesodermal or endodermal cell lineage. We were able to predict the proportion of cardiomyocytes many days before cells manifest the differentiated phenotype. The analysis of cell populations undergoing a critical state transition thus affords a tool to forecast cell fate outcomes and can be used to optimize differentiation protocols to obtain desired cell populations.single-cell analysis | critical state transitions | iPSC to cardiomyocyte differentiation | differentiation efficiency | prediction

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Section: Resultsmentioning

confidence: 99%

Cell population structure prior to bifurcation predicts efficiency of directed differentiation in human induced pluripotent cells

Bargaje

Trachana

Shelton

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

118

View full text Add to dashboard Cite

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“…), and the downstream Snail and E-cadherin canonical pathway regulating epicardial EMT (Brade et al, 2013;Von Gise and Pu, 2012). The significance of cytoskeletal dynamics in controlling EMT is less frequently addressed.…”

Section: Introductionmentioning

confidence: 99%

“…However, there are several lines of evidence that point to a role for NMII in EMT. First, epicardial EMT features an extensive actin cytoskeletal reorganization where epicardial cells lose their epithelial apical-basal polarity and strong cell-cell adhesions, to acquire mesenchymal front-rear polarity and focal adhesions resulting in increased motility and invasiveness (Brade et al, 2013;Von Gise and Pu, 2012). NMII plays important roles in regulating actin-cytoskeletal structures (Heissler and Manstein, 2013;Vicente-Manzanares et al, 2009).…”

Section: Introductionmentioning

confidence: 99%

“…The development of a functional heart is orchestrated by various lineages of cardiac cells including epicardial, endocardial, myocardial and cardiac non-myocyte interstitial cells (Tirziu et al, 2010;Brade et al, 2013), each of which contains the cytoplasmic contractile protein nonmuscle myosin IIB (NMIIB; heavy chain encoded by MYH10) . The epicardium is a single cell layer of mesothelial cells that covers the outer surface of the heart and protects the integrity of the myocardium (Von Gise and Pu, 2012).…”

Section: Introductionmentioning

confidence: 99%

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Nonmuscle myosin IIB regulates epicardial integrity and epicardium-derived mesenchymal cell maturation

Sung

Yang

et al. 2017

Journal of Cell Science

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Nonmuscle myosin IIB (NMIIB; heavy chain encoded by MYH10) is essential for cardiac myocyte cytokinesis. The role of NMIIB in other cardiac cells is not known. Here, we show that NMIIB is required in epicardial formation and functions to support myocardial proliferation and coronary vessel development. Ablation of NMIIB in epicardial cells results in disruption of epicardial integrity with a loss of E-cadherin at cell-cell junctions and a focal detachment of epicardial cells from the myocardium. NMIIB-knockout and blebbistatin-treated epicardial explants demonstrate impaired mesenchymal cell maturation during epicardial epithelial-mesenchymal transition. This is manifested by an impaired invasion of collagen gels by the epicardium-derived mesenchymal cells and the reorganization of the cytoskeletal structure. Although there is a marked decrease in the expression of mesenchymal genes, there is no change in Snail (also known as Snai1) or E-cadherin expression. Studies from epicardiumspecific NMIIB-knockout mice confirm the importance of NMIIB for epicardial integrity and epicardial functions in promoting cardiac myocyte proliferation and coronary vessel formation during heart development. Our findings provide a novel mechanism linking epicardial formation and epicardial function to the activity of the cytoplasmic motor protein NMIIB.

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“…Las Células de la Cresta Neural (CCN) corresponden a una población celular multipotente originada de la porción dorsal del tubo neural, desde donde migran a través del organismo en desarrollo para dar origen a una amplia variedad de estructuras (Zhang et al, 2014) o participar en su formación, entre ellas el corazón, en donde más allá de la diferenciación en fenotipos celulares responsables de la formación de estructuras cardíacas, modulan factores de crecimiento y transcripción, coordinando así la acción de otros linajes celulares en el desarrollo del aparato cardiovascular (Brade et al, 2013 maciones de otros sistemas, reflejo de la variedad de funciones que desempeñan en el desarrollo embrionario (Nelms et al, 2011).…”

Section: Introductionunclassified

Células de la Cresta Neural y su Relación con Cardiopatía Congénita: Revisión Sistemática de la Literatura

Ramos

Roa

2016

Int. J. Morphol.

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ROA, I. Células de la cresta neural y su relación con cardiopatía congénita: revisión sistemática de la literatura. Int. J. Morphol., 34(2):489-494, 2016. RESUMEN:Las cardiopatías congénitas corresponden al grupo de anomalías del desarrollo que se presentan con mayor frecuencia. Durante el desarrollo cardíaco participan distintos linajes celulares, donde destacan las Células de la Cresta Neural (CCN) por su amplia gama de derivados embriológicos y la susceptibilidad de afectar a múltiples sistemas si su función es alterada. El objetivo fue determinar el rol que cumplen las CCN durante el desarrollo cardíaco y las cardiopatías congénitas asociadas. Se diseñó un estudio descriptivo en base a una revisión sistemática de la literatura de las bases de datos MEDLINE y Scopus, utilizando la combinación de términos MeSH: ("Heart Diseases/congenital" OR "Heart Diseases/embriology" OR "Heart Diseases/etiology" OR "Heart Disesaes/ epidemiology") AND ("Neural Crest/abnormalities"). Se restringió la búsqueda a artículos de los últimos 10 años. De un total de 35 artículos obtenidos, 22 fueron incluidos para su revisión por estar relacionados con los objetivos de este estudio, excluyéndose duplicados entre bases de datos. Posteriormente se hizo un análisis individual y en conjunto de la información obtenida de los artículos seleccionados. La evidencia indica la participación directa o indirecta de las CCN durante la formación de las estructuras derivadas del polo arterioso del corazón en desarrollo, los grandes vasos arteriales y sus ramas colaterales, así como en su inervación y sistema de conducción. La alteración del funcionamiento normal de las CCN produce fenotipos cardíacos alterados, siendo la persistencia del tronco arterioso, doble salida ventricular derecha, defectos septales interventriculares y malformación de los aparatos valvares aórtico y pulmonar, los más frecuentes.PALABRAS CLAVE: Cardiopatía congénita; Cresta neural; Células de la Cresta neural; Embriología. INTRODUCCIÓNLa cardiopatía congénita corresponde a toda malformación cardíaca presente al momento del nacimiento, secundaria a alteraciones producidas durante la organogénesis del corazón (Neeb et al., 2013). Es sin duda, la anomalía de más altaincidencia en recién nacidos, con una tasa en Chile de entre 4 a 12 por cada 1000 nacidos vivos y una mortalidad correspondiente a 1/3 del total de muertes causadas por anomalías congénitas y a 1/10 del total de todas las muertes en menores de un año (MINSAL, 2010), valores similares a los registrados en otras poblaciones a nivel mundial (van der Linde et al., 2011).El desarrollo cardíaco es un proceso complejo donde participan y se coordinan diferentes poblaciones celulares; lo que explica, en parte, la alta prevalencia de anomalías congénitas asociadas a defectos cardíacos (Paul et al., 2014). Las Células de la Cresta Neural (CCN) corresponden a una población celular multipotente originada de la porción dorsal del tubo neural, desde donde migran a través del organismo en desarrollo para dar origen a una amplia va...

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Embryonic Heart Progenitors and Cardiogenesis

Cited by 204 publications

References 108 publications

Cell population structure prior to bifurcation predicts efficiency of directed differentiation in human induced pluripotent cells

Cell population structure prior to bifurcation predicts efficiency of directed differentiation in human induced pluripotent cells

Nonmuscle myosin IIB regulates epicardial integrity and epicardium-derived mesenchymal cell maturation

Células de la Cresta Neural y su Relación con Cardiopatía Congénita: Revisión Sistemática de la Literatura

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