Cardiomyocyte maturation: advances in knowledge and implications for regenerative medicine

Nature Reviews Cardiology, Journal Year: 2020, Volume and Issue: 17(6), P. 341 - 359

Published: Feb. 3, 2020

Language: Английский

---

Cardiomyocyte Maturation

Circulation Research, Journal Year: 2020, Volume and Issue: 126(8), P. 1086 - 1106

Published: April 9, 2020

Maturation is the last phase of heart development that prepares organ for strong, efficient, and persistent pumping throughout mammal's lifespan. This process characterized by structural, gene expression, metabolic, functional specializations in cardiomyocytes as transits from fetal to adult states. Cardiomyocyte maturation gained increased attention recently due defects pluripotent stem cell-derived cardiomyocyte, its antagonistic effect on myocardial regeneration, potential contribution cardiac disease. Here, we review major hallmarks ventricular cardiomyocyte summarize key regulatory mechanisms promote coordinate these cellular events. With advances technical platforms used research, expect significant progress future will deepen our understanding this lead better novel therapeutic strategies

Language: Английский

---

Evidence for hormonal control of heart regenerative capacity during endothermy acquisition

Science, Journal Year: 2019, Volume and Issue: 364(6436), P. 184 - 188

Published: March 8, 2019

Tissue regenerative potential displays striking divergence across phylogeny and ontogeny, but the underlying mechanisms remain enigmatic. Loss of mammalian cardiac correlates with cardiomyocyte cell-cycle arrest polyploidization as well development postnatal endothermy. We reveal that diploid abundance 41 species conforms to Kleiber's law-the ¾-power law scaling metabolism bodyweight-and inversely standard metabolic rate, body temperature, serum thyroxine level. Inactivation thyroid hormone signaling reduces mouse polyploidization, delays exit, retains in adults. Conversely, exogenous hormones inhibit zebrafish heart regeneration. Thus, our findings suggest loss capacity adult mammals is triggered by increasing may be a trade-off for acquisition

Language: Английский

---

Early Regenerative Capacity in the Porcine Heart

Circulation, Journal Year: 2018, Volume and Issue: 138(24), P. 2798 - 2808

Published: July 20, 2018

The adult mammalian heart has limited ability to repair itself after injury. Zebrafish, newts, and neonatal mice can regenerate cardiac tissue, largely by myocyte (CM) proliferation. It is unknown whether hearts of young large mammals regenerate.We examined the regenerative capacity pig in animals (ages 2, 3, or 14 days postnatal) myocardial infarction sham procedure. Myocardial scar left ventricular function were determined magnetic resonance imaging echocardiography. Bromodeoxyuridine pulse-chase labeling, histology, immunohistochemistry, Western blotting performed study cell proliferation, sarcomere dynamics, cytokinesis quantify fibrosis. RNA-sequencing was also performed.After infarction, there early sustained recovery wall thickness absence fibrosis 2-day-old pigs. In contrast, older developed full-thickness scarring, thinned walls, did not recover function. Genome-wide analyses infarct zone revealed a strong transcriptional signature 14-day-old that absent pigs, which instead had enrichment for genes. regenerating younger animals, up 10% CMs border showed evidence DNA replication associated with markers division disassembly.Hearts have capacity, likely driven division, but this potential lost immediately birth.

Language: Английский

---

YAP Partially Reprograms Chromatin Accessibility to Directly Induce Adult Cardiogenesis In Vivo

Developmental Cell, Journal Year: 2019, Volume and Issue: 48(6), P. 765 - 779.e7

Published: Feb. 14, 2019

Language: Английский

---

The epicardium as a hub for heart regeneration

Nature Reviews Cardiology, Journal Year: 2018, Volume and Issue: 15(10), P. 631 - 647

Published: June 27, 2018

Language: Английский

---

Polyploidy: A Biological Force From Cells to Ecosystems

Trends in Cell Biology, Journal Year: 2020, Volume and Issue: 30(9), P. 688 - 694

Published: July 6, 2020

Communication across disciplinary boundaries to identify common themes of polyploidy has been extremely limited.Identifying commonalities that derive from shared polyploid cellular processes disparate fields inquiry holds promise breakthroughs in numerous areas – biodiversity and biocomplexity medicine agriculture.We propose new directions integrate research on toward confronting interdisciplinary grand challenges the 21st century. Polyploidy, resulting duplication entire genome an organism or cell, greatly affects genes genomes, cells tissues, organisms, even ecosystems. Despite wide-reaching importance polyploidy, communication at different scales almost nonexistent. However, a critical need remains understand organismal diversity, levels biological organization, agriculture. Here, we review current understanding suborganismal levels, elements, Polyploidy [whole-genome (WGD); see Glossary], defined as having three more sets chromosomes, influences organisms all clades eukaryotic life ecosystems (Figure 1). The intersection these axes scale offers opportunity for insight innovation. Yet, underexplored many contexts, its roles impact phylogeny are unclear. This lack clarity derives, part, very limited scales. genomics era accelerated provided platform dialogue potential synergy. We argue cross-disciplinary approaches crucial identifying functions regulation polyploidy. can arise both levels. At level, unreduced gametes (e.g., diploid instead haploid) formed during meiosis fuse generate whole-organism Organismal is major driver extends life, deep history recent past [1.Soltis D.E. et al.Polyploidy angiosperm diversification.Am. J. Bot. 2009; 96: 336-348Crossref PubMed Scopus (861) Google Scholar,2.Van De Peer Y. al.The evolutionary significance polyploidy.Nat. Rev. Genet. 2017; 18: 411-424Crossref (742) Scholar]. Most, if not all, extant species (including our own) carry signature least one ancient WGD [2.Van Within programmed aberrant events also increase ploidy specific somatic cell lineages, often playing important role tissue differentiation animals organ development plants 1) [3.Orr-Weaver T.L. When bigger better: organogenesis.Trends 2015; 31: 307-315Abstract Full Text PDF (170) Scholar,4.Schoenfelder K.P. Fox D.T. expanding implications polyploidy.J. Cell Biol. 209: 485-491Crossref (139) New examples tissues continue emerge, such mammary growth mammalian lactation [5.Rios A.C. al.Essential novel population binucleated epithelial lactation.Nat. Commun. 2016; 7: 11400Crossref (58) Scholar] repairing kidney bladder [6.Wang al.Polyploid superficial maintain urothelial barrier produced via incomplete cytokinesis endoreplication.Cell Rep. 2018; 25 (e4): 464-477Abstract (35) Scholar,7.Lazzeri E. al.Endocycle-related tubular hypertrophy progenitor proliferation recover renal function after acute injury.Nat. 9: 1344Crossref (129) Events leading increases include variant cycles endoreplication cell–cell fusion reviewed elsewhere [8.Edgar B.A. al.Endocycles: recurrent innovation post-mitotic growth.Nat. Mol. 2014; 15: 197-210Crossref (228) Scholar,9.Aguilar P.S. al.Genetic basis cell-cell mechanisms.Trends 2013; 29: 427-437Abstract (173) diverse size [4.Schoenfelder Scholar,10.Marshall W.F. al.What determines size?.BMC 2012; 10: 101Crossref (143) essentially universal property results decreased surface/volume ratio. full polyploidy-driven changes uncertain, but emerging data suggest profound shifts following polyploidization. Moreover, highlight here, may be manifested effect environmental stress (i.e., increased rates polyploidization) adaptation it. intimate relationship makes study increasingly cells, whole must respond rapid their biotic abiotic environments. Greater into distinctive unravel strategies fight some world's most pressing social crises. These efforts sustaining ecosystem services, increasing diversifying agricultural yield rapidly changing environments, advancing biotechnology medical interventions. particularly true with respect diseases cancer, where now appreciated player promoting suppressing tumor progression [11.Zack T.I. al.Pan-cancer patterns copy number alteration.Nat. 45: 1134-1140Crossref (1180) Scholar, 12.Bielski C.M. al.Genome doubling shapes evolution prognosis advanced cancers.Nat. 50: 1189-1195Crossref (240) 13.Laughney A.M. al.Dynamics heterogeneity derived clonal karyotypic evolution.Cell 12: 809-820Abstract (69) 14.Lin Y.H. al.Mice numbers hepatocytes regenerative capacity develop fewer hepatocellular carcinomas chronic liver injury.Gastroenterology. 2020; 158: 1698-1712.e14Abstract (36) 15.Wilkinson P.D. state restricts hepatocyte regeneration mice.Hepatology. 2019; 69: 1242-1258Crossref (73) long compartmentalized, investigators evolution, ecology, genomics, agriculture, other branches biology few, any, interactions, despite asking similar questions about drivers consequences cellular, tissue, organ, likely result plethora recurring downstream effects settings, including gene expression size, epigenetic remodeling, modifications subcellular networks interaction, altered responses Thus, alter phenotype, only level organization level. Going forward, collaboration aimed doubling/polyploidy will unify currently fields, unearth insights, paradigm shifts. present two clearly illustrate animals. interaction among scientists studying multiple organizational large phylogenetic distances. high low temperature, water availability, salinity) induce meiotic gamete production [16.Ramsey Schemske D.W. Pathways, mechanisms, formation flowering plants.Annu. Ecol. Syst. 1998; 467-501Crossref (1453) 17.Mason A.S. al.Production viable male Brassica interspecific hybrids genotype stimulated by cold temperatures.BMC Plant 2011; 11: 103Crossref (96) 18.Pécrix al.Polyploidization mechanisms: temperature environment Rosa sp.J. Exp. 62: 3587-3597Crossref (124) 19.de Storme N. Arabidopsis cold-induced destabilization postmeiotic radial microtubule arrays.Plant Physiol. 160: 1808-1826Crossref (98) doubling, immediately line. stress-induced plays agriculture horticulture generating synthetic polyploids manner lead ultimately lineages nature. Comparably, stresses wounding viral infection Scholar,20.Losick V.P. contribute wound healing adult Drosophila epithelium.Curr. 23: 2224-2232Abstract (126) 21.Tamori Deng W.M. Tissue repair through competition compensatory postmitotic epithelia.Dev. Cell. 28: 350-363Abstract 22.Payne E.H. mitotic death distinct HIV-1 Vpr-driven outcomes tubule cells.J. Virol. 92e01718-17Crossref (7) 23.Li T.N. al.Intrahepatic hepatitis B virus surface antigen induces hyperploidy failure cytokinesis.J. Pathol. 245: 502-513Crossref (17) Scholar], which mass enlarged cells. response represents alternative division. In animals, several injury have described vertebrate kidney, bladder, epicardium well insect [20.Losick Scholar,24.Lazzeri al.Surviving failure: polyploidization proliferation.Trends Med. 25: 366-381Abstract (46) Scholar,25.Neiman M. al.Endopolyploidy animal ecology evolution.Biol. 92: 234-247Crossref Such injury-triggered enable regrowth without compromising integrity division [26.Cohen al.Fizzy-Related dictates cycle switch hindgut.eLife. 7e38327Crossref (33) provide necessary mechanical force [27.Cao al.Tension creates wavefront leads epicardial tissue.Dev. 42 600-615Abstract Similarly, plants, (cell activation mitosis) pathogens crops powdery mildew, root knot nematodes [28.Paige K.N. Overcompensation, stress, endoreduplication.Am. 105: 1105-1108Crossref (13) Scholar]) mutualistic associations mycorrhizal fungi nitrogen-fixing rhizobia) engage [29.Smant G. al.Parallel adaptations host enabling feeding obligate facultative plant parasitic nematodes.Plant 93: 686-702Crossref Scholar,30.Forrester N.J. obtain greater fitness benefits nutrient acquisition mutualism.New Phytol. https://doi.org/10.1111/nph.16574Crossref (11) While various shortcuts cycle, biotrophic interactions involve penetration upregulation same genes, suggesting effectors involved generic reactions Furthermore, work nodules house rhizobia demonstrated transcription related dynamic epigenome [31.Nagymihály al.Ploidy-dependent symbiotic correlate expression.Proc. Natl. Acad. Sci. U. S. A. 114: 4543-4548Crossref (37) Interestingly, it proposed plasticity (endoreplication) trade off [25.Neiman Scholar,32.Pacey E.K. influence experimentally induced relationships between endopolyploidy thaliana.Ecol. Evol. 198-216Crossref routes mitigate stress. tissue-level WGD, molecular connections stress-sensing remain unknown. above-mentioned set linking awaiting discovery. For example, could endoreplication-mediated programs associated stresses, hypothesis tested human systems, clear injury. researcher investigating injury-induced heart, recently shown block therapeutic [33.Han L. al.Lamin B2 regulate cardiomyocyte nuclei myocardial regeneration.Dev. 53: 42-59.e11Abstract 34.González-Rosa J.M. al.Myocardial heart zebrafish.Dev. 44 (e7): 433-446Abstract (142) 35.Gan P. al.Cardiomyocyte regeneration.Annu. 82: 45-61Crossref (38) 36.Patterson al.Frequency mononuclear cardiomyocytes underlies natural variation regeneration.Nat. 49: 1346-1353Crossref (178) much researchers similarly leaves tissues. Collaborative this area potentially lead, injured organs arrest cancer WGD. Genome individual effects, regardless context. First, copies each chromosome enhance genetic diversity. diversity then seed additional expression, epigenetics, networks, proteome, overall diversity/versatility line fuel that, once filtered selection, adaptation. Stress polyploidy; substantial reveal provides adaptive advantage under unstable, stressful As promotes salinity tolerance [37.Schoenfelder al.Indispensable pre-mitotic endocycles promote aneuploidy rectum.Development. 141: 3551-3560Crossref (44) [38.Liu al.Root-zone-specific sensitivity K+- Ca2+-permeable channels H2O2 ion homeostasis salinized hexaploid Ipomoea trifida.J. 70: 1389-1405Crossref (29) 39.Chao D.-Y. al.Polyploids exhibit higher potassium uptake Arabidopsis.Science. 341: 658-659Crossref (227) 40.Ruiz al.Tetraploidy enhances ability exclude chloride carrizo citrange seedlings.J. 205: 1-10Crossref (40) sweet potato, better K+/Na+ saline conditions than diploids, begging question whether mechanism operate broadly. stable environment, gradual successfully explain aspects evolution. buffering imposed duplicate consequent delay fixation beneficial deleterious alleles, nature genomes drive change. evolvability quickly local/regional populations massive accompanied meteor Cretaceous–Paleogene boundary [41.Fawcett J.A. al.Plants double might had chance survive Cretaceous-Tertiary extinction event.Proc. 106: 5737-5742Crossref (452) able projected climate change scenarios remainder adaptability lines implications. when occurs normally diploid. cancers, occurrence significantly shape tumors perhaps genomic instability Scholar,42.Storchova Z. Ploidy stability yeast.Yeast. 421-430Crossref Scholar,43.Chen giant (PGCCs): evil roots cancer. Curr.Cancer Drug Targets. 19: 360-367Crossref (82) therefore cancer-driving mutations drug resistance Scholar,12.Bielski Scholar,44.Coward Harding Size does matter: why targets war cancer.Front. Oncol. 4: 123Crossref (132) support idea, was found roughly one-third solid prevalent (>50%) metastatic disease [45.Priestley whole-genome analyses tumours.Nature. 575: 210-216Crossref (380) Likewise, (followed mis-segregation chromosomes) Candida albicans, pathogenic fungus, occur antifungal fluconazole (FLC) [46.Harrison B.D. al.A tetraploid intermediate precedes aneuploid yeasts exposed fluconazole.PLoS 12e1001815Crossref (109) creating FLC-resistant progeny. By contrast oft-described negative attributes [47.Torres E.M. al.Effects physiology haploid yeast.Science. 2007; 317: 916-924Crossref (641) Scholar,48.Sheltzer al.Aneuploidy drives 333: 1026-1030Crossref (289) aneuploids were show little cost. Aneuploidy occasional opportunities [49.Zhu al.Cellular aneuploidy.Dev. 44: 420-431Abstract (88) Scholar,50.Sheltzer Amon paradox: costs incorrect karyotype.Trends 27: 446-453Abstract (145) Experimental systems offer mechanisms. yeast (single cells), adapt faster haploids especially frequent stronger [51.Selmecki yeast.Nature. 519: 349-352Crossref (268) just beginning how agronomic success; structures trichomes, fruits, Scholar,52.Barow Meister Endopolyploidy differently correlated systematics, strategy size.Plant Environ. 2003; 26: 571-584Crossref above discussion centers fueling adaptability, converse occur. duplicated minimize phenotypic variation, because buffer against [53.Stebbins G.L. Chromosomal Evolution Higher Plants. Arnold, 1972Google Scholar,54.Ohno Gene Duplication. Springer, 1970Crossref newly organism, advantageous, accumulate over time, eventually reaching frequency disadvantageous [55.Otto S.P. Whitton Polyploid incidence evolution.Annu. 2000; 34: 401-437Crossref (1666) Scholar,56.Otto polyploidy.Cell. 131: 452-462Abstract (782) rarely copies, reduced inbreeding depression [56.Otto 57.Charlesworth D. Charlesworth B. Inbreeding consequences.Annu. 1987; 237-268Crossref (2431) 58.Hedrick P.W. Genetic load mating system homosporous ferns.Evolution. 41: 1282-1289Crossref 59.Soltis Soltis success polyploids.Proc. 97: 7051-7057Crossref (798) example demonstration prevents driven homozygous recessive suppressor [60.Zhang tumor-suppressive liver.Dev. (e5): 447-459Abstract (90) Overall, similarities conferred revealed emphasizing coordinated, research. integration promises further distances while clarifying unique process, species. collaborations underlying 'rules' cut disciplines (from medicine). knowing help address outstanding 'moon shot' settings (see Outstanding Questions). reminded 'nothing sense except light evolution' [61.Dobzhansky T. Biology, organismic.Am. Zool. 1964; 443-452Crossref With mind, replaying 'genome duplication' tape fast-growing should insights regarding confers selective advantage. done 'evolve resequence' experiments, and/or artificial experimental models, (re)sequenced generations selection [62.Yao al.Using digital polyploidy.PLoS One. 14e0220257Crossref (19) Scholar,63.Burny C. al.Secondary evolve resequencing: confirmation putative phenotyping.Genome 151-159Crossref (8) approach clues, facilitates conditions. mathematical modeling possible dynamics perspective ecological, developmental, settings. Applications broad. forward-time simulations accommodate ecoevolutionary mixed-ploidy could, inform us fate frequency/severity drought fungal parasite exposure agent Importantly, suggests optimally converge narrow range [13.Laughney supporting validity health evolutionary/modeling field. That normal malignant possess, time possessed, genome, intrigued 100 years. siloed; medical, agricultural, biologists who contact. integrative needed fully facets intricacies 'life genomes.' joint ventures Undoubtedly, seeks own discoveries spanning medicine, evolution/ecology. Polyploidy's link novelty [64.Albertin W. Marullo fungi: duplication.Proc. R. Soc. 279: 2497-2509Crossref within nature, domestication experiments untapped resource advances Knowledge gained coupled synthesizing neopolyploids, technologies solve global problems. anticipate, soon edit [65.Shan al.Application CRISPR/Cas9 Tragopogon (Asteraceae), model polyploidy.Mol. Resour. 1427-1443Crossref Scholar,66.Shan al.Considerations adapting nongenetic systems.Appl. 8e11314Crossref (22) engineer functions, mitigation greenhouse gases plastics pollution repair. thus broad challenge, 'polyploidy 2030,' next decade. effort would tree areas, biology, working collectively meaningful synthesis subsystems. 2030 central well-being. Additional funding accomplish goals. well-studied oncogenes, Ras family Scholar,67.Hobbs G.A. al.RAS isoforms glance.J. 129: 1287-1292Crossref (491) yet lags behind mutations. Central answered include, to, biodiversity, addition improvements medicine. Sharing data, knowledge, expertise catalyze roles, rules, impacts cooperation century, maintaining health, food security, services face change.Outstanding QuestionsHow complexity regulatory affect (both diseased), organisms?What advantageous emergence stress?What characteristics exploited preventive purposes?Why ecological niches transient, process 'diploidization' return part state? How organisms? What stress? purposes? Why Y.V.dP. acknowledges European Research Council (ERC) Union's Horizon 2020 program (grant agreement no. 833522). F. National Institutes Health GM118447). supported US Science Foundation Division Environmental Biology (NSF DEB) grants 1912180 1834496 T-L.A. NSF Integrative Systems IOS) grant 1923234 D.S. authors thank participants 2019 Ghent conference input comments. performance growth) certain environment; selection. mutualists form long-term mycorrhizae). generation [68.Wolfe K.H. Yesterday's mystery diploidization.Nat. 2001; 2: 333-341Crossref (580) 69.Wendel J.F. wondrous plants.Am. 102: 1753-1756Crossref (216) 70.Soltis al.Polyploidy: pitfalls paths paradigm.Am. 103: 1146-1166Crossref (189) 71.Robertson F.M. al.Lineage-specific rediploidization time-lags diversification.Genome 111Crossref (89) 72.Duncan A.W. conveyor mature source variation.Nature. 2010; 467: 707-710Crossref (365) reciprocal processes; is, vice versa. general term truncated completing division, cell. DNA sequence–independent alterations chromatin, condensation active/repressive histone chemical modifications, expression. independently sequence. depends amount of, generate, whereby compensated biochemical phenotype. reduction trait due close relatives selfing) alleles loss heterozygosity. referring chromosomes given nucleus. manipulation processes. I, homolog disjunction fails reduced. any content.

Language: Английский

---

Model systems for regeneration: zebrafish

Development, Journal Year: 2019, Volume and Issue: 146(18)

Published: Sept. 15, 2019

Tissue damage can resolve completely through healing and regeneration, or produce permanent scarring loss of function. The response to tissue varies across tissues between species. Determining the natural mechanisms behind regeneration in model organisms that regenerate well help us develop strategies for recovery species with poor regenerative capacity (such as humans). zebrafish (Danio rerio) is one most accessible vertebrate models study regeneration. In this Primer, we highlight tools available zebrafish, provide an overview underlying system discuss future perspectives field.

Language: Английский

---

Polyploidy in Cardiomyocytes

Circulation Research, Journal Year: 2020, Volume and Issue: 126(4), P. 552 - 565

Published: Feb. 13, 2020

The hallmark of most cardiac diseases is the progressive loss cardiomyocytes. In perinatal period, cardiomyocytes still proliferate, and heart shows capacity to regenerate upon injury. adult heart, however, actual rate cardiomyocyte renewal too low efficiently counteract substantial cell caused by mammals, growth number expansion changes enlargement soon after birth, coinciding with a period in which increase their DNA content multinucleation nuclear polyploidization. Although hypertrophy often associated these processes, whether polyploidy prerequisite or consequence hypertrophic unclear. Both benefits over proliferative physiological role are enigmatic. Interestingly, hearts animal species regenerative dominantly comprise diploid cardiomyocytes, raising hypothesis that poses barrier for proliferation subsequent regeneration. On contrary, there also evidence self-duplication multinucleated myocytes, suggesting more complex picture Polyploidy not restricted but occurs other types body. this review, we explore biological relevance different tissues acquire insight into its specific Furthermore, speculate about how might relate

Language: Английский

---

Gene therapy knockdown of Hippo signaling induces cardiomyocyte renewal in pigs after myocardial infarction

Science Translational Medicine, Journal Year: 2021, Volume and Issue: 13(600)

Published: June 30, 2021

Gene therapy–mediated disruption of Hippo signaling results in tissue renewal and improved function pigs after myocardial infarction.

Language: Английский

---