Cardiopoietic Factors

Noseda, Michela; Peterkin, Tessa; Simões, Filipa C.; Patient, Roger; Schneider, Michael

doi:10.1161/circresaha.110.223792

Cited by 110 publications

(61 citation statements)

References 315 publications

(331 reference statements)

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“…Like ETS2, MESP1 blocked the appearance of bone morphogenetic protein 2 (BMP2), BMP4, and PDGFRα (Fig. 2E), which are associated with the induction of the cardiac progenitor program in ES cells (24,25). These KDR + and PECAM1 + cells did not induce terminal cardiogenesis.…”

Section: Resultsmentioning

confidence: 93%

Transcription factors ETS2 and MESP1 transdifferentiate human dermal fibroblasts into cardiac progenitors

Islas

Liu

Weng

et al. 2012

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

192

149

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Unique insights for the reprograming of cell lineages have come from embryonic development in the ascidian Ciona, which is dependent upon the transcription factors Ci-ets1/2 and Ci-mesp to generate cardiac progenitors. We tested the idea that mammalian v-ets erythroblastosis virus E26 oncogene homolog 2 (ETS2) and mesoderm posterior (MESP) homolog may be used to convert human dermal fibroblasts into cardiac progenitors. Here we show that murine ETS2 has a critical role in directing cardiac progenitors during cardiopoiesis in embryonic stem cells. We then use lentivirus-mediated forced expression of human ETS2 to convert normal human dermal fibroblasts into replicative cells expressing the cardiac mesoderm marker KDR + . However, although neither ETS2 nor the purported cardiac master regulator MESP1 can by themselves generate cardiac progenitors de novo from fibroblasts, forced coexpression of ETS2 and MESP1 or cell treatment with purified proteins reprograms fibroblasts into cardiac progenitors, as shown by the de novo appearance of core cardiac transcription factors, Ca 2+ transients, and sarcomeres. Our data indicate that ETS2 and MESP1 play important roles in a genetic network that governs cardiopoiesis.cardiogenesis | fibroblast reprograming | protein transduction | kinetic imaging

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Section: Resultsmentioning

confidence: 93%

Transcription factors ETS2 and MESP1 transdifferentiate human dermal fibroblasts into cardiac progenitors

Islas

Liu

Weng

et al. 2012

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

192

149

View full text Add to dashboard Cite

show abstract

“…The induction of mesoderm formation and its further specification into cardiac mesoderm and distinct populations of cardiac progenitor cells is primarily controlled by three families of extracellular signaling molecules: wingless integrated (Wnt), fibroblast growth factor (FGF) and transforming growth factor-beta (TGFβ) superfamily ligands, which include Wnt3a, bone morphogenetic protein 4 (BMP4), Nodal and activin A (Fig. 2) (reviewed by Noseda et al, 2011). These ligands are expressed in gradients, thereby patterning the developing embryo and sending either activating or inhibitory instructive cues to the underlying cells, depending on the spatiotemporal context.…”

Section: Specification Of the Cardiac Mesodermmentioning

confidence: 99%

“…These ligands are expressed in gradients, thereby patterning the developing embryo and sending either activating or inhibitory instructive cues to the underlying cells, depending on the spatiotemporal context. The future cardiac field is specified in response to this combination of signaling factors and downstream transcriptional events, which eventually lead to the expression of cardiac-specific factors in a defined population of mesodermal cells (reviewed by Noseda et al, 2011).…”

Section: Specification Of the Cardiac Mesodermmentioning

confidence: 99%

How to make a cardiomyocyte

et al. 2014

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During development, cardiogenesis is orchestrated by a family of heart progenitors that build distinct regions of the heart. Each region contains diverse cell types that assemble to form the complex structures of the individual cardiac compartments. Cardiomyocytes are the main cell type found in the heart and ensure contraction of the chambers and efficient blood flow throughout the body. Injury to the cardiac muscle often leads to heart failure due to the loss of a large number of cardiomyocytes and its limited intrinsic capacity to regenerate the damaged tissue, making it one of the leading causes of morbidity and mortality worldwide. In this Primer we discuss how insights into the molecular and cellular framework underlying cardiac development can be used to guide the in vitro specification of cardiomyocytes, whether by directed differentiation of pluripotent stem cells or via direct lineage conversion. Additional strategies to generate cardiomyocytes in situ, such as reactivation of endogenous cardiac progenitors and induction of cardiomyocyte proliferation, will also be discussed.

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“…This invariably involves a complex reciprocal molecular dialog between neighboring cells (Noseda et al 2011). A mainstay concept in developmental biology is that the adoption of a lineage fate invokes a global lockdown of possibilities for alternative fates (Davidson et al 2002).…”

Section: Restriction Of Developmental Potential and Cell Fatementioning

confidence: 99%

Genetic Networks Governing Heart Development

Waardenberg

Ramialison

Bouveret

et al. 2014

Cold Spring Harbor Perspectives in Medicine

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Animal genomes contain a code for construction of the body plan from a fertilized egg. Understanding how genome information is deciphered to create the complex multilayered regulatory systems that drive organismal development, and which become altered in disease, is one of the greatest challenges in the biological sciences. The development of methods that effectively represent and communicate the complexity inherent in gene regulatory networks remains a major barrier. This review introduces the philosophy of systems biology and discusses recent progress in understanding the development of the heart at a systems biology level. SYSTEMS BIOLOGYS ystems biology is an emerging multidisciplinary field embedded in large-scale data initiatives that seeks to understand the complex interactions occurring within biological systems. The recent increase in popularity of systems biology has been the consequence of technological advances that have flowed from the sequencing of the human genome (Lander et al. 2001). However, the last decade of research has reinforced the notion that to understand biological networks we need to do more than just describe genome organization. A major finding that has reshaped our view of biology is the realization that transcriptional complexity rather than genome size or the number of protein-coding genes is the evolutionary driver for increased biological diversity (Britten and Davidson 1969;Carninci et al. 2005;Fantom Consortium et al. 2014).Network theory hypothesizes that specific interaction patterns in biology have logic and functional significance. The discovery that uni-

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Cardiopoietic Factors

Cited by 110 publications

References 315 publications

Transcription factors ETS2 and MESP1 transdifferentiate human dermal fibroblasts into cardiac progenitors

Transcription factors ETS2 and MESP1 transdifferentiate human dermal fibroblasts into cardiac progenitors

How to make a cardiomyocyte

Genetic Networks Governing Heart Development

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