Abstract
Cardiomyocyte loss after injury results in adverse remodelling and fibrosis, inevitably leading to heart failure. The ERBB2–Neuregulin and Hippo–YAP signalling pathways are key mediators of heart regeneration, yet the crosstalk between them is unclear. We demonstrate that transient overexpression of activated ERBB2 in cardiomyocytes (OE CMs) promotes cardiac regeneration in a heart failure model. OE CMs present an epithelial–mesenchymal transition (EMT)-like regenerative response manifested by cytoskeletal remodelling, junction dissolution, migration and extracellular matrix turnover. We identified YAP as a critical mediator of ERBB2 signalling. In OE CMs, YAP interacts with nuclear-envelope and cytoskeletal components, reflecting an altered mechanical state elicited by ERBB2. We identified two YAP-activating phosphorylations on S352 and S274 in OE CMs, which peak during metaphase, that are ERK dependent and Hippo independent. Viral overexpression of YAP phospho-mutants dampened the proliferative competence of OE CMs. Together, we reveal a potent ERBB2-mediated YAP mechanotransduction signalling, involving EMT-like characteristics, resulting in robust heart regeneration.
This is a preview of subscription content, access via your institution
Access options
Access Nature and 54 other Nature Portfolio journals
Get Nature+, our best-value online-access subscription
$29.99 / 30 days
cancel any time
Subscribe to this journal
Receive 12 print issues and online access
$209.00 per year
only $17.42 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
Data availability
The RNA-seq data were deposited in the Gene Expression Omnibus under accession code GSE144391. The mass spectrometry data have been deposited in ProteomeXchange under accession code PXD020731. All other data supporting the findings of this study are available from the corresponding author on reasonable request. Source data are provided with this paper.
References
Tzahor, E. & Poss, K. D. Cardiac regeneration strategies: staying young at heart. Science 356, 1035–1039 (2017).
Poss, K. D., Wilson, L. G. & Keating, M. T. Heart regeneration in zebrafish. Science 298, 2188–2190 (2002).
Porrello, E. R. et al. Transient regenerative potential of the neonatal mouse heart. Science 331, 1078–1080 (2011).
Jopling, C. et al. Zebrafish heart regeneration occurs by cardiomyocyte dedifferentiation and proliferation. Nature 464, 606–609 (2010).
Leone, M. & Engel, F. B. Advances in heart regeneration based on cardiomyocyte proliferation and regenerative potential of binucleated cardiomyocytes and polyploidization. Clin. Sci. 133, 1229–1253 (2019).
Itou, J. et al. Migration of cardiomyocytes is essential for heart regeneration in zebrafish. Development 139, 4133–4142 (2012).
Harvey, R. P., Wystub-Lis, K., del Monte-Nieto, G., Graham, R. M. & Tzahor, E. Cardiac regeneration therapies—targeting Neuregulin 1 signalling. Heart Lung Circ. 25, 4–7 (2016).
D’Uva, G. et al. ERBB2 triggers mammalian heart regeneration by promoting cardiomyocyte dedifferentiation and proliferation. Nat. Cell Biol. 17, 627–638 (2015).
Gemberling, M., Karra, R., Dickson, A. L. & Poss, K. D. Nrg1 is an injury-induced cardiomyocyte mitogen for the endogenous heart regeneration program in zebrafish. eLife 4, e05871 (2015).
Polizzotti, B. D. et al. Neuregulin stimulation of cardiomyocyte regeneration in mice and human myocardium reveals a therapeutic window. Sci. Transl. Med. 7, 281ra45 (2015).
Heallen, T. et al. Hippo pathway deficiency reverses systolic heart failure after infarction. Nature 550, 260–264 (2017).
von Gise, A. et al. YAP1, the nuclear target of Hippo signaling, stimulates heart growth through cardiomyocyte proliferation but not hypertrophy. Proc. Natl Acad. Sci. USA 109, 2394–2399 (2012).
Morikawa, Y. et al. Actin cytoskeletal remodeling with protrusion formation is essential for heart regeneration in Hippo-deficient mice. Sci. Signal. 8, ra41 (2015).
Monroe, T. O. et al. YAP partially reprograms chromatin accessibility to directly induce adult cardiogenesis in vivo. Dev. Cell 48, 765–779 (2019).
Xin, M. et al. Hippo pathway effector Yap promotes cardiac regeneration. Proc. Natl Acad. Sci. USA 110, 13839–13844 (2013).
Panciera, T., Azzolin, L., Cordenonsi, M. & Piccolo, S. Mechanobiology of YAP and TAZ in physiology and disease. Nat. Rev. Mol. Cell Biol. 18, 758–770 (2017).
Dupont, S. et al. Role of YAP/TAZ in mechanotransduction. Nature 474, 179–183 (2011).
Ragni, C. V. et al. Amotl1 mediates sequestration of the Hippo effector Yap1 downstream of Fat4 to restrict heart growth. Nat. Commun. 8, 14582 (2017).
Hirai, M. et al. Adaptor proteins NUMB and NUMBL promote cell cycle withdrawal by targeting ERBB2 for degradation. J. Clin. Invest. 127, 569–582 (2017).
Li, J. et al. Alpha-catenins control cardiomyocyte proliferation by regulating yap activity. Circ. Res. 116, 70–79 (2015).
Nakada, Y. et al. Hypoxia induces heart regeneration in adult mice. Nature 54, 222–227 (2016).
Marín-juez, R. et al. Fast revascularization of the injured area is essential to support zebrafish heart regeneration. Proc. Natl. Acad. Sci. USA 113, 11237–11242 (2016).
Das, S. et al. A unique collateral artery development program promotes neonatal heart regeneration. Cell 176, 1128–1142 (2019).
Honkoop, H. et al. Single-cell analysis uncovers that metabolic reprogramming by ErbB2 signaling is essential for cardiomyocyte proliferation in the regenerating heart. eLife 8, e50163 (2019).
Fukuda, R. et al. Metabolic modulation regulates cardiac wall morphogenesis in zebrafish. eLife 8, e50161 (2019).
Lamouille, S., Xu, J. & Derynck, R. Molecular mechanisms of epithelial–mesenchymal transition. Nat. Rev. Mol. Cell Biol. 15, 178–196 (2014).
Zhao, B. et al. Inactivation of YAP oncoprotein by the Hippo pathway is involved in cell contact inhibition and tissue growth control. Genes Dev. 21, 2747–2761 (2007).
Zhao, B., Li, L., Tumaneng, K., Wang, C. Y. & Guan, K. L. A coordinated phosphorylation by Lats and CK1 regulates YAP stability through SCFβ-TRCP. Genes Dev. 24, 72–85 (2010).
Ni, L., Zheng, Y., Hara, M., Pan, D. & Luo, X. Structural basis for Mob1-dependent activation of the core Mst–Lats kinase cascade in Hippo signaling. Genes Dev. 29, 1416–1431 (2015).
Moroishi, T. et al. A YAP/TAZ-induced feedback mechanism regulates Hippo pathway homeostasis. Genes Dev. 29, 1271–1284 (2015).
Hertig, V. et al. Nestin expression is dynamically regulated in cardiomyocytes during embryogenesis. J. Cell. Physiol. 233, 3218–3229 (2018).
Stroud, M. J., Banerjee, I., Veevers, J. & Chen, J. LINC complex proteins in cardiac structure, function, and disease. Circ. Res. 31, 538–548 (2014).
Kirby, T. J. & Lammerding, J. Emerging views of the nucleus as a cellular mechanosensor. Nat. Cell Biol. 20, 373–381 (2018).
Swift, J. et al. Nuclear lamin-A scales with tissue stiffness and enhances matrix-directed differentiation. Science 341, 965–966 (2013).
Cho, S., Irianto, J. & Discher, D. E. Mechanosensing by the nucleus: from pathways to scaling relationships. J. Cell Biol. 216, 305–315 (2017).
Torvaldson, E., Kochin, V. & Eriksson, J. E. Phosphorylation of lamins determine their structural properties and signaling functions. Nucleus 6, 166–171 (2015).
Robison, P. et al. Detyrosinated microtubules buckle and bear load in contracting cardiomyocytes. Science 352, aaf0659 (2016).
Delmar, M. & Liang, F.-X. Connexin43, and the regulation of intercalated disc function. Heart Rhythm 9, 835–838 (2012).
Yang, S. et al. CDK1 phosphorylation of YAP promotes mitotic defects and cell motility and is essential for neoplastic transformation. Cancer Res. 73, 6722–6733 (2013).
Lin, Z. & Pu, W. T. Releasing YAP from an α-catenin trap increases cardiomyocyte proliferation. Circ. Res. 116, 9–11 (2015).
Morikawa, Y., Heallen, T., Leach, J., Xiao, Y. & Martin, J. F. Dystrophin–glycoprotein complex sequesters Yap to inhibit cardiomyocyte proliferation. Nature 547, 227–231 (2017).
Zhang, R. et al. In vivo cardiac reprogramming contributes to zebrafish heart regeneration. Nature 498, 497–501 (2013).
del Monte-Nieto, G. et al. Control of cardiac jelly dynamics by NOTCH1 and NRG1 defines the building plan for trabeculation. Nature 557, 439–471 (2018).
Von Gise, A. & Pu, W. T. Endocardial and epicardial epithelial to mesenchymal transitions in heart development and disease. Circ. Res. 110, 1628–1645 (2012).
Nieto, M. A., Huang, R. Y. Y. J., Jackson, R. A. A. & Thiery, J. P. P. EMT: 2016. Cell 166, 21–45 (2016).
Combs, M. D. & Yutzey, K. E. Heart valve developement: regulatory networks in development and disease. Circ. Res. 105, 408–421 (2009).
Gabisonia, K. et al. MicroRNA therapy stimulates uncontrolled cardiac repair after myocardial infarction in pigs. Nature 569, 418–422 (2019).
Aragona, M. et al. A mechanical checkpoint controls multicellular growth through YAP/TAZ regulation by actin-processing factors. Cell 154, 1047–1059 (2013).
Elosegui-Artola, A. et al. Force triggers YAP nuclear entry by regulating transport across nuclear pores. Cell 171, 1397–1410 (2017).
Shiu, J. Y., Aires, L., Lin, Z. & Vogel, V. Nanopillar force measurements reveal actin-cap-mediated YAP mechanotransduction. Nat. Cell Biol. 20, 262–270 (2018).
Komuro, A., Nagai, M., Navin, N. E. & Sudol, M. WW domain-containing protein YAP associates with ErbB-4 and acts as a co-transcriptional activator for the carboxyl-terminal fragment of ErbB-4 that translocates to the nucleus. J. Biol. Chem. 278, 33334–33341 (2003).
Haskins, J. W., Nguyen, D. X. & Stern, D. F. Neuregulin 1–activated ERBB4 interacts with YAP to induce Hippo pathway target genes and promote cell migration. Sci. Signal. 355, ra116 (2014).
Bui, D. A. et al. Cytokinesis involves a nontranscriptional function of the Hippo pathway effector YAP. Sci. Signal. 9, ra23 (2016).
Zhao, Y. et al. YAP-induced resistance of cancer cells to antitubulin drugs is modulated by a hippo-independent pathway. Cancer Res. 74, 4493–4503 (2014).
Plouffe, S. W. et al. The Hippo pathway effector proteins YAP and TAZ have both distinct and overlapping functions in the cell. J. Biol. Chem. 293, 11230–11240 (2018).
Reddy, B. V. V. G. & Irvine, K. D. Regulation of hippo signaling by EGFR–MAPK signaling through ajuba family proteins. Dev. Cell 24, 451–471 (2013).
Hino, N. et al. ERK-mediated mechanochemical waves direct collective cell polarization. Dev. Cell 53, 646–660 (2020).
Sohal, D. S. et al. Temporally regulated and tissue-specific gene manipulations in the adult and embryonic heart using a tamoxifen-inducible Cre protein. Circ. Res. 89, 20–25 (2001).
Zhang, N. et al. The Merlin/NF2 tumor suppressor functions through the YAP oncoprotein to regulate tissue homeostasis in mammals. Dev. Cell 19, 27–38 (2010).
Martin, M. Cutadapt removes adapter sequesnces from high-throughput sequencing reads. EMBnet 17, 5–7 (2011).
Kim, D. et al. TopHat2: accurate alignment of transcriptomes in the presence of insertions, deletions and gene fusions. Genome Biol. 14, 1–13 (2013).
Anders, S. et al. Count-based differential expression analysis of RNA sequencing data using R and Bioconductor. Nat. Protoc. 8, 1765–1786 (2013).
Love, M. I., Huber, W. & Anders, S. Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol. 15, 550 (2014).
Wisniewski, J., Zougman, A., Nagaraj, N. & Mann, M. Universal sample preparation method for proteome analysis. Nat. Methods 6, 359–362 (2009).
Tamary, E. et al. Chlorophyll catabolism precedes changes in chloroplast structure and proteome during leaf senescence. Plant Direct 3, 1–18 (2019).
Milo-Cochavi, S. et al. The response to the DNA damaging agent methyl methanesulfonate in a fungal plant pathogen. Fungal Biol. 123, 408–422 (2019).
Shalit, T., Elinger, D., Savidor, A., Gabashvili, A. & Levin, Y. MS1-based label-free proteomics using a quadrupole orbitrap mass spectrometer. J. Proteome Res. 14, 1979–1986 (2015).
Cox, Jurgen & Mann, M. MaxQuant enables high peptide identification rates, individualized p.p.b.-range mass accuracies and proteome-wide protein quantification. Nat. Biotechnol. 26, 1367–1372 (2008).
Acknowledgements
This study has been supported by grants to E.T. from the European Research Council (ERC StG grant no. 281289, CM turnover, and ERC AdG grant no. 788194, CardHeal), ERA-CVD CARDIO-PRO, EU Horizon 2020 research and innovation programme REANIMA, the U.S.–Israel Binational Science Foundation (BSF; to both E.T. and J.F.M.), the Israel Science Foundation (ISF), Foundation Leducq Transatlantic Network of Excellence and Minerva foundation, with funding from the Federal German Ministry for Education and Research. We thank the Benoziyo Endowment Fund for the Advancement of Science, Head of the Yad Abraham Research Center for Cancer Diagnostics and Therapy, Zuckerman STEM Leadership Program, Dr. Dvora and Haim Teitelbaum Endowment Fund and Daniel S. Shapiro Cardiovascular Research Fund. This work was supported by grants from the National Institutes of Health (grant nos HL127717, HL130804 and HL118761 (J.F.M.)), Vivian L. Smith Foundation (J.F.M.) and State of Texas funding (J.F.M.). We thank O. Singer for help with the AAV preparations, G. Friedlander for RNA-seq analysis and input, and N. Priel for teaching ‘trackmate’ software usage.
Author information
Authors and Affiliations
Contributions
A.A. and E.T. conceived and designed the experiments. A.A., with help from A.Shakked, carried out most of the experiments and analysed the data. Specifically, A.Shakked helped with the animal studies, tissue culture work, RT–qPCR and cloning of YAP mutants into AAV viruses and all associated work and analysis. K.B.U. helped with the animal studies, RNA-seq preparation and analysis. A.Savidor and Y.L. performed the proteomic analysis. A.G. helped with the image analysis. D.K. and D.L. performed the myocardial infarction and echocardiographic analysis. O-Y.R. helped with the functional gelatin-degradation assays and migration time-lapse microscopy. Y.M. helped with the YAP5SA heart sections. J.D. provided custom-made and pYAP S274 antibody. B.G. and J.F.M. contributed to the planning and discussion of the project. E.T. supervised the entire project. A.A. and E.T. wrote the manuscript with contributions from all of the authors.
Corresponding author
Ethics declarations
Competing interests
The authors declare no competing interests.
Additional information
Peer review information Peer reviewer reports are available.
Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Extended data
Extended Data Fig. 1 Transient ERBB2 activation in injured hearts (HF model) promotes functional improvement.
a, % Scar quantification for the 3WPMI time point (relates to Fig. 1a, orange arrow) for adult WT (n=5) and OE (n=4) hearts, p=0.180. Statistics were determined by two-tailed t-test. (b-d) Cardiac parameters derived from echocardiographic analysis. Green window represents duration of ERBB2 activation. b, Left ventricular anterior wall (LVAW) thickness, p<0.0001. c, Stroke volume, p=0.0002 (d) Cardiac output, p=0.04, in WT (n=16), OE (n=11) and Sham (n=5) hearts. Statistics, one-way ANOVA followed by Tukey’s multiple comparisons test. Data represent mean ± s.e.m. For statistical source data, see Source Data Extended Data Figure 1.
Extended Data Fig. 2 EMT hallmarks are upregulated in OE hearts.
a, Analysis of bulk RNA- seq of adult WT–MI (n=4) and OE–MI (n=4) hearts using GSEA hallmark module (relates to Fig. 1h). Bar plot depict the normalized enrichment scores (NES). b-e, RNA- seq derived heat map of the indicated genes belonging to the EMT hallmark (as shown in (a) and Fig. 1h). Genes were annotated as (b) ECM composition (c) ECM modulators (d) Transcription factors and (e) Transmembranal and secreted proteins. FC to the right indicates OE/WT fold change of the detected transcripts by RNA- seq using a threshold FC≥1.5 and p adjusted ≤0.05. Statistics were determined by DESeq2, and adjusted for multiple testing using the procedure of Benjamini and Hochberg. f, Representative image in adult WT and OE hearts. Scale bar, 50 µm.
Extended Data Fig. 3 ERBB2 activation results in reduced CM connectivity and sarcomeric organization, partially depending on YAP.
a, Representative IF images and (b) Representative Haematoxylin & Eosin stain for adult WT, OE and OE-KD heart sections. Scale bar 50µm. c, Quantification of normalized sarcomeric fluorescence intensity for WT (n=3), OE (n=3) and OE-KD (n=3) adult hearts, p=0.047. d, Quantification of normalized interstitial gaps between CMs, for WT (n=3), OE (n=3) and OE-KD (n=3) adult hearts. WT compared to OE, p=0.0018. OE compared to OE-KD, p=0.007. e, Representative IF images of WT (n=3), OE (n=3) and OE-KD (n=3) adult hearts. Scale bar 100µm. Insets highlight separate channels as indicated, white and yellow arrow heads point to connections between CMs with intact and mispatterened CDH2, correspondingly, at the termini of CMs. Inset Scale bar 10µm. Data represent mean ± s.e.m. All figure statistics were determined by one-way ANOVA followed by Tukey’s multiple comparisons test. For statistical source data, see Source Data Extended Data Figure 3.
Extended Data Fig. 4 YAP Co-IP–MS binding partners.
a, Heat map of YAP enrichment in Yap Co-IP and IgG reactions for WT (n=4) and OE (n=4) adult hearts, as described in Fig. 5a. FC indicates fold change between IP and IgG reactios. b, Heat map of differential YAP binding partners between WT (n=4) and OE (n=4) adult hearts. FC indicates fold change between OE to WT IP reactions of the detected protein by Mass Spec. All displayed results are of statistical significance p ≤ 0.05 between OE and WT IP reactions, which were non-significantly different between OE and WT IgG reactions (similar background). All figure statistics were determined by two-tailed t-test.
Extended Data Fig. 5 Phosphorylation of YAP on S274 and S352 is prevalent in OE hearts and peaks during mitosis.
a, WB analysis of YAP on the soluble fraction of adult WT/OE hearts. b, WB analysis of pYAP S274 on the soluble fraction of adult WT/OE hearts. c, WB analysis of pYAP S352 on the soluble fraction of adult WT/OE hearts. d, WB analysis of YAP on whole cell lysates (includes cytoskeletal components underrepresented in soluble extracts) of adult WT/OE hearts. Blue and red arrow heads point to the usual (“upper”) and below 63kDa (“lower”) bands. e, YAP IP (and IgG) from WT/OE hearts blotted for YAP and pYAP S274. Purple circles represent cut-out bands analysed by Mass-Spec in (f). f, Peptide-spectrum match (#PSM) for YAP analysed by Mass-Spec of (e), an experiment performed once. g, h, Diagram of murine YAP (YAP2L, 488aa) (Plus Myc-DDK tag, as purchased) in (g) and human YAP (YAP2L, 504aa) in (h). Domains indicated above, Hippo phosphorylation sites denoted in grey, and S274/S352 (S289/367 in human) phosphorylation sites circled in red. i, j, Representative images of P7 WT/OE cardiac cultures. Scale bar 50µm. WT and OE insets highlight with an arrow a non-CM, and a CM, at metaphase with peaking pYAP S274/S352 stain. Scale bar 10 µm. k, Quantification of P7 OE Aurkb+ CMs (blue curve) and pYAP S352 mitotic localization (orange curve) at stages of mitosis. Lower panel shows pYAP S352-Aurkb mitotic overlap. n=2274 CMs, from 3 OE hearts. l, Representative image at metaphase of P7 OE cardiac cultures Scale bar 50µm. m, Representative image of embryonic WT E16.5 heart sections. Scale bar 50µm. Inset arrows point to CMs in metaphase. Inset scale bar 10µm. n, Representative image of OE and 5SA adult hearts. White, yellow arrows point to metaphase, pre-metaphase CMs, correspondingly. Scale bar, 10µm. Uncropped blots in panels a, b, c, d, e and numerical source data in panel k are provided in Source Data Extended Data Figure 5.
Extended Data Fig. 6 ERK interacts with YAP and drives YAP S274 phopshorylation and morphological changes in ERBB2-OE CMs.
a, b, Representative IF images of P7 WT/OE cardiac cultures upon vehicle (DMSO) or ERK-i treatment. Scale bar 50µm. c–e, quantification of morphological features of circularity (p), Axial ratio (q), and solidity, (r) upon vehicle (DMSO) or ERK-i (n=127) treatment, of P7 WT (n=123) or OE (n=126) CMs derived from 4 WT and 4 OE P7 hearts. For circularity, WT compared to OE, p=0.0220, OE compared to OE-ERK-i, p=0.0498. For axial ratio, WT compared to OE, p=0.0029, OE compared to OE-ERK-i, p=0.0199. For solidity, WT compared to OE, p=0.0008. OE compared to OE-ERK-i, p=0.0001. f, Quantification of PLA foci in adult cardiac sections, with individual corresponding technical controls for WT (n=6) and OE (n=6) hearts. Data represent mean ± s.e.m. All figure statistics were determined by one-way ANOVA followed by Tukey’s multiple comparisons test. (∗) if P ≤0.05, (∗∗) if P <0.01, (∗∗∗) if P <0.001 and (∗∗∗∗) if P <0.0001. For statistical source data, see Source Data Extended Data Figure 6.
Supplementary information
Supplementary Video 1
Time-lapse movie (96 h) of a P7 WT cardiac culture showing CMs tagged with tdTomato fluorescent protein and non-CMs in phase. n = 6 independent experiments.
Supplementary Video 2
Time-lapse movie (96 h) of a P7 OE cardiac culture showing CMs tagged with tdTomato fluorescent protein and non-CMs in phase. n = 4 independent experiments.
Supplementary Table
Table of supplementary information regarding the primer sequences and antibodies used in the study.
Source data
Source Data Fig. 1
Statistical source data of Fig. 1
Source Data Fig. 2
Unprocessed western blots of Fig. 2
Source Data Fig. 2
Statistical source data of Fig. 2
Source Data Fig. 3
Unprocessed western blots of Fig. 3
Source Data Fig. 3
Statistical source data of Fig. 3
Source Data Fig. 4
Unprocessed western blots of Fig. 4
Source Data Fig. 4
Statistical source data of Fig. 4
Source Data Fig. 5
Unprocessed western blots of Fig. 5
Source Data Fig. 5
Statistical source data of Fig. 5
Source Data Fig. 6
Unprocessed western blots of Fig. 6
Source Data Fig. 6
Statistical source data of Fig. 6
Source Data Extended Data Fig. 1
Statistical source data of Extended Data Fig. 1
Source Data Extended Data Fig. 3
Statistical source data of Extended Data Fig. 3
Source Data Extended Data Fig. 5
Unprocessed western blots of Extended Data Fig. 5
Source Data Extended Data Fig. 5
Statistical source data of Extended Data Fig. 5
Source Data Extended Data Fig. 6
Statistical source data of Extended Data Fig. 6
Rights and permissions
About this article
Cite this article
Aharonov, A., Shakked, A., Umansky, K.B. et al. ERBB2 drives YAP activation and EMT-like processes during cardiac regeneration. Nat Cell Biol 22, 1346–1356 (2020). https://doi.org/10.1038/s41556-020-00588-4
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/s41556-020-00588-4
This article is cited by
-
Animal models to study cardiac regeneration
Nature Reviews Cardiology (2024)
-
Toward drug-induced heart regeneration
Nature Cardiovascular Research (2024)
-
Role of PATJ in stroke prognosis by modulating endothelial to mesenchymal transition through the Hippo/Notch/PI3K axis
Cell Death Discovery (2024)
-
Regeneration of the heart: from molecular mechanisms to clinical therapeutics
Military Medical Research (2023)
-
Optogenetic control of YAP can enhance the rate of wound healing
Cellular & Molecular Biology Letters (2023)