Reprogramming for cardiac regeneration

Raynaud, Christophe M.; Ahmad, Faizzan S.; Allouba, Mona; Abou-Saleh, Haissam; Lui, Kathy O.; Yacoub, Magdi H.

doi:10.5339/gcsp.2014.44

Cited by 5 publications

(3 citation statements)

References 179 publications

(185 reference statements)

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“…DKK1 is also known as a direct target of Wnt signaling and is secreted from PSCs stimulated by CHIR 4 , 25 . In cardiac development in vivo, Wnt activation is required for mesoderm differentiation, and subsequent Wnt suppression by inhibitors such as DKK1 and Cerberus, secreted from the anterior visceral endoderm, is necessary for cardiomyogenesis 26 , 27 . Our ELISA results showed that DKK1, DKK4 and Cerberus are secreted by cells and that the concentration peaked at day 3.…”

Section: Discussionmentioning

confidence: 99%

Auto/paracrine factors and early Wnt inhibition promote cardiomyocyte differentiation from human induced pluripotent stem cells at initial low cell density

Takahi

Ohnuma

2021

Sci Rep

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Cardiomyocytes derived from human induced pluripotent stem cells (hiPSCs) have received increasing attention for their clinical use. Many protocols induce cardiomyocytes at an initial high cell density (confluence) to utilize cell density effects as hidden factors for cardiomyocyte differentiation. Previously, we established a protocol to induce hiPSC differentiation into cardiomyocytes using a defined culture medium and an initial low cell density (1% confluence) to minimize the hidden factors. Here, we investigated the key factors promoting cardiomyocyte differentiation at an initial low cell density to clarify the effects of cell density. Co-culture of hiPSCs at an initial low cell density with those at an initial high cell density showed that signals secreted from cells (auto/paracrine factors) and not cell–cell contact signals, played an important role in cardiomyocyte differentiation. Moreover, although cultures with initial low cell density showed higher expression of anti-cardiac mesoderm genes, earlier treatment with a Wnt production inhibitor efficiently suppressed the anti-cardiac mesoderm gene expression and promoted cardiomyocyte differentiation by up to 80% at an initial low cell density. These results suggest that the main effect of cell density on cardiomyocyte differentiation is inhibition of Wnt signaling at the early stage of induction, through auto/paracrine factors.

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Section: Discussionmentioning

confidence: 99%

Auto/paracrine factors and early Wnt inhibition promote cardiomyocyte differentiation from human induced pluripotent stem cells at initial low cell density

Takahi

Ohnuma

2021

Sci Rep

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“…(Raynaud et al, Global Cardiology Science and Practice, 2014:44 alapján). 3 Multipotens őssejtnek nevezzük azt a korlátozott differenciációs képességekkel rendelkező sejtet, amely általában egy adott szövet sejtjeit képes előállítani, de más típusú szövetet vagy ivarsejteket nem tud létrehozni. Ezek az úgynevezett szöveti őssejtek.…”

Section: áBra Az őSsejtek Hierarchiájaunclassified

Humán embrionális őssejtek vizsgálata: mezenchimális differenciáció és ABC transzporterek

Varga¹

2017

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“…These processes are tightly regulated to guarantee the timely generation of the appropriate number and type of stem and progenitor cells that give rise to a healthy organism. Nevertheless, the various developmental processes do not cease beyond embryogenesis; instead they become tissue‐specific in the adult organism in order to renew cellular pools that may have become depleted, injured or simply require substitution for the maintenance of homeostasis (in ). A number of proteins that are involved in binary cell fate decisions are now under scientific scrutiny and Geminin, being among the most enigmatic, has attracted scientific interest in its own merit.…”

Section: Introductionmentioning

confidence: 99%

Concise Review: Geminin—A Tale of Two Tails: DNA Replication and Transcriptional/Epigenetic Regulation in Stem Cells

et al. 2016

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Molecular mechanisms governing maintenance, commitment, and differentiation of stem cells are largely unexploited. Molecules involved in the regulation of multiple cellular processes are of particular importance for stem cell physiology, as they integrate different signals and coordinate cellular decisions related with self-renewal and fate determination. Geminin has emerged as a critical factor in DNA replication and stem cell differentiation in different stem cell populations. Its inhibitory interaction with Cdt1, a member of the prereplicative complex, ensures the controlled timing of DNA replication and, consequently, genomic stability in actively proliferating cells. In embryonic as well as somatic stem cells, Geminin has been shown to interact with transcription factors and epigenetic regulators to drive gene expression programs and ultimately guide cell fate decisions. An ever-growing number of studies suggests that these interactions of Geminin and proteins regulating transcription are conserved among metazoans. Interactions between Geminin and proteins modifying the epigenome, such as members of the repressive Polycomb group and the SWI/SNF proteins of the permissive Trithorax, have long been established. The complexity of these interactions, however, is only just beginning to unravel, revealing key roles on maintaining stem cell self-renewal and fate specification. In this review, we summarize current knowledge and give new perspectives for the role of Geminin on transcriptional and epigenetic regulation, alongside with its regulatory activity in DNA replication and their implication in the regulation of stem and progenitor cell biology. STEM CELLS 2017;35:299-310 SIGNIFICANCE STATEMENTThe review focuses on the roles of Geminin in embryonic and somatic stem cells. More specifically, we have addressed how Geminin, through its regulatory roles in transcriptional and epigenetic control, impacts stem cell self-renewal versus differentiation decisions. In recent years, we and other researchers have studied extensively the transcriptional programs affected by Geminin in various developmental stages and tissues using murine models. However, what we wish to emphasize in this review-as well as to summarize findings in order to aid future studies-is the network of proteins that Geminin associates with at the epigenomic level. These interactions are critical for cellular pluri/multi-potency and differentiation decisions of stem and progenitor cells for maintenance of homeostasis. Last, but not least, we provide links between the transcriptional/epigenetic roles of Geminin and its more traditional role as a regulator of DNA replication. We believe that these two otherwise distinct roles of this protein are interconnected and we anticipate that our views will stimulate future studies with cutting edge research investing into how Geminin could be fine-tuned to assist tissue engineering in medical applications.

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Reprogramming for cardiac regeneration

Cited by 5 publications

References 179 publications

Auto/paracrine factors and early Wnt inhibition promote cardiomyocyte differentiation from human induced pluripotent stem cells at initial low cell density

Auto/paracrine factors and early Wnt inhibition promote cardiomyocyte differentiation from human induced pluripotent stem cells at initial low cell density

Humán embrionális őssejtek vizsgálata: mezenchimális differenciáció és ABC transzporterek

Concise Review: Geminin—A Tale of Two Tails: DNA Replication and Transcriptional/Epigenetic Regulation in Stem Cells

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