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ERRγ agonist under mechanical stretching manifests hypertrophic cardiomyopathy phenotypes of engineered cardiac tissue through maturation

Fujiwara, Yuya Miki, Kenji Deguchi, Kohei Naka, Yuki Sasaki, Masako Sakoda, Ayaka Narita, Megumi Imaichi, Sachiko Sugo, Tsukasa Funakoshi, Shunsuke Nishimoto, Tomoyuki Imahashi, Kenichi Yoshida, Yoshinori 京都大学 DOI:10.1016/j.stemcr.2023.09.003

2023.11.14

概要

Engineered cardiac tissue (ECT) using human induced pluripotent stem cell-derived cardiomyocytes is a promising tool for modeling heart disease. However, tissue immaturity makes robust disease modeling difficult. Here, we established a method for modeling hypertrophic cardiomyopathy (HCM) malignant (MYH7 R719Q) and nonmalignant (MYBPC3 G115∗) pathogenic sarcomere gene mutations by accelerating ECT maturation using an ERRγ agonist, T112, and mechanical stretching. ECTs treated with T112 under 10% elongation stimulation exhibited more organized and mature characteristics. Whereas matured ECTs with the MYH7 R719Q mutation showed broad HCM phenotypes, including hypertrophy, hypercontraction, diastolic dysfunction, myofibril misalignment, fibrotic change, and glycolytic activation, matured MYBPC3 G115∗ ECTs displayed limited phenotypes, which were primarily observed only under our new maturation protocol (i.e., hypertrophy). Altogether, ERRγ activation combined with mechanical stimulation enhanced ECT maturation, leading to a more accurate manifestation of HCM phenotypes, including non-cardiomyocyte activation, consistent with clinical observations.

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参考文献

Authors/Task Force members, Elliott, P.M., Anastasakis, A., Borger,

M.A., Borggrefe, M., Cecchi, F., Charron, P., Hagege, A.A., Lafont,

A., Limongelli, G., et al. (2014). 2014 ESC Guidelines on diagnosis

and management of hypertrophic cardiomyopathy: the Task Force

for the Diagnosis and Management of Hypertrophic Cardiomyopathy of the European Society of Cardiology (ESC). Eur. Heart J. 35,

2733–2779. https://doi.org/10.1093/eurheartj/ehu284.

Cohn, R., Thakar, K., Lowe, A., Ladha, F.A., Pettinato, A.M.,

Romano, R., Meredith, E., Chen, Y.S., Atamanuk, K., Huey, B.D.,

and Hinson, J.T. (2019). A Contraction Stress Model of Hypertrophic Cardiomyopathy due to Sarcomere Mutations. Stem Cell

Rep. 12, 71–83. https://doi.org/10.1016/j.stemcr.2018.11.015.

Fujiwara, Y., Deguchi, K., Miki, K., Nishimoto, T., and Yoshida, Y.

(2021). A Method for Contraction Force Measurement of hiPSCDerived Engineered Cardiac Tissues. Methods Mol. Biol. 2320,

171–180. https://doi.org/10.1007/978-1-0716-1484-6_17.

Funakoshi, S., Fernandes, I., Mastikhina, O., Wilkinson, D., Tran,

T., Dhahri, W., Mazine, A., Yang, D., Burnett, B., Lee, J., et al.

(2021). Generation of mature compact ventricular cardiomyocytes

from human pluripotent stem cells. Nat. Commun. 12, 3155.

https://doi.org/10.1038/s41467-021-23329-z.

Helms, A.S., Thompson, A.D., Glazier, A.A., Hafeez, N., Kabani, S.,

Rodriguez, J., Yob, J.M., Woolcock, H., Mazzarotto, F., Lakdawala,

N.K., et al. (2020). Spatial and Functional Distribution of

MYBPC3 Pathogenic Variants and Clinical Outcomes in Patients

With Hypertrophic Cardiomyopathy. Circ. Genom. Precis. Med.

13, 396–405. https://doi.org/10.1161/CIRCGEN.120.002929.

Ho, C.Y., Charron, P., Richard, P., Girolami, F., Van SpaendonckZwarts, K.Y., and Pinto, Y. (2015). Genetic advances in sarcomeric

cardiomyopathies: state of the art. Cardiovasc. Res. 105, 397–408.

https://doi.org/10.1093/cvr/cvv025.

Karbassi, E., Fenix, A., Marchiano, S., Muraoka, N., Nakamura, K.,

Yang, X., and Murry, C.E. (2020). Cardiomyocyte maturation: advances in knowledge and implications for regenerative medicine.

Nat. Rev. Cardiol. 17, 341–359. https://doi.org/10.1038/s41569019-0331-x.

Knight, W.E., Cao, Y., Lin, Y.H., Chi, C., Bai, B., Sparagna, G.C.,

Zhao, Y., Du, Y., Londono, P., Reisz, J.A., et al. (2021). Maturation

of Pluripotent Stem Cell-Derived Cardiomyocytes Enables

Modeling of Human Hypertrophic Cardiomyopathy. Stem Cell

Rep. 16, 519–533. https://doi.org/10.1016/j.stemcr.2021.01.018.

Lan, F., Lee, A.S., Liang, P., Sanchez-Freire, V., Nguyen, P.K., Wang,

L., Han, L., Yen, M., Wang, Y., Sun, N., et al. (2013). Abnormal calcium handling properties underlie familial hypertrophic cardiomyopathy pathology in patient-specific induced pluripotent

stem cells. Cell Stem Cell 12, 101–113. https://doi.org/10.1016/j.

stem.2012.10.010.

Leonard, A., Bertero, A., Powers, J.D., Beussman, K.M., Bhandari, S.,

Regnier, M., Murry, C.E., and Sniadecki, N.J. (2018). Afterload promotes maturation of human induced pluripotent stem cell derived

cardiomyocytes in engineered heart tissues. J. Mol. Cell. Cardiol.

118, 147–158. https://doi.org/10.1016/j.yjmcc.2018.03.016.

Lompre, A.M., Mercadier, J.J., Wisnewsky, C., Bouveret, P., Pantaloni, C., D’Albis, A., and Schwartz, K. (1981). Species- and agedependent changes in the relative amounts of cardiac myosin isoenzymes in mammals. Dev. Biol. 84, 286–290. https://doi.org/10.

1016/0012-1606(81)90396-1.

Ma, Z., Huebsch, N., Koo, S., Mandegar, M.A., Siemons, B., Boggess,

S., Conklin, B.R., Grigoropoulos, C.P., and Healy, K.E. (2018). Contractile deficits in engineered cardiac microtissues as a result of

MYBPC3 deficiency and mechanical overload. Nat. Biomed. Eng.

2, 955–967. https://doi.org/10.1038/s41551-018-0280-4.

Maron, B.J., Gardin, J.M., Flack, J.M., Gidding, S.S., Kurosaki, T.T.,

and Bild, D.E. (1995). Prevalence of hypertrophic cardiomyopathy

in a general population of young adults. Echocardiographic analysis of 4111 subjects in the CARDIA Study. Coronary Artery Risk

Development in (Young) Adults. Circulation 92, 785–789.

https://doi.org/10.1161/01.cir.92.4.785.

Marston, S., Copeland, O., Jacques, A., Livesey, K., Tsang, V.,

McKenna, W.J., Jalilzadeh, S., Carballo, S., Redwood, C., and Watkins, H. (2009). Evidence from human myectomy samples that

MYBPC3 mutations cause hypertrophic cardiomyopathy through

haploinsufficiency. Circ. Res. 105, 219–222. https://doi.org/10.

1161/CIRCRESAHA.109.202440.

Miki, K., Deguchi, K., Nakanishi-Koakutsu, M., Lucena-Cacace, A.,

Kondo, S., Fujiwara, Y., Hatani, T., Sasaki, M., Naka, Y., Okubo, C.,

et al. (2021). ERRgamma enhances cardiac maturation with

T-tubule formation in human iPSC-derived cardiomyocytes. Nat.

Commun. 12, 3596. https://doi.org/10.1038/s41467-021-23816-3.

Stem Cell Reports j Vol. 18 j 2108–2122 j November 14, 2023 2121

Milani-Nejad, N., and Janssen, P.M.L. (2014). Small and large animal models in cardiac contraction research: advantages and disadvantages. Pharmacol. Ther. 141, 235–249. https://doi.org/10.

1016/j.pharmthera.2013.10.007.

Miron, A., Lafreniere-Roula, M., Steve Fan, C.P., Armstrong, K.R.,

Dragulescu, A., Papaz, T., Manlhiot, C., Kaufman, B., Butts, R.J.,

Gardin, L., et al. (2020). A Validated Model for Sudden Cardiac

Death Risk Prediction in Pediatric Hypertrophic Cardiomyopathy.

Circulation 142, 217–229. https://doi.org/10.1161/CIRCULATIONAHA.120.047235.

Mosqueira, D., Mannhardt, I., Bhagwan, J.R., Lis-Slimak, K., Katili,

P., Scott, E., Hassan, M., Prondzynski, M., Harmer, S.C., Tinker, A.,

et al. (2018). CRISPR/Cas9 editing in human pluripotent stem cellcardiomyocytes highlights arrhythmias, hypocontractility, and

energy depletion as potential therapeutic targets for hypertrophic

cardiomyopathy. Eur. Heart J. 39, 3879–3892. https://doi.org/10.

1093/eurheartj/ehy249.

Mosqueira, D., Smith, J.G.W., Bhagwan, J.R., and Denning, C.

(2019). Modeling Hypertrophic Cardiomyopathy: Mechanistic Insights and Pharmacological Intervention. Trends Mol. Med. 25,

775–790. https://doi.org/10.1016/j.molmed.2019.06.005.

Bhavsar, P.K., Dhoot, G.K., Cumming, D.V., Butler-Browne, G.S.,

Yacoub, M.H., and Barton, P.J. (1991). Developmental expression

of troponin I isoforms in fetal human heart. FEBS Lett. 292, 5–8.

https://doi.org/10.1016/0014-5793(91)80820-s.

Piquereau, J., and Ventura-Clapier, R. (2018). Maturation of Cardiac Energy Metabolism During Perinatal Development. Front.

Physiol. 9, 959. https://doi.org/10.3389/fphys.2018.00959.

Ronaldson-Bouchard, K., Ma, S.P., Yeager, K., Chen, T., Song, L., Sirabella, D., Morikawa, K., Teles, D., Yazawa, M., and Vunjak-Novakovic, G. (2018). Advanced maturation of human cardiac tissue

grown from pluripotent stem cells. Nature 556, 239–243. https://

doi.org/10.1038/s41586-018-0016-3.

2122 Stem Cell Reports j Vol. 18 j 2108–2122 j November 14, 2023

Ruan, J.L., Tulloch, N.L., Razumova, M.V., Saiget, M., Muskheli, V.,

Pabon, L., Reinecke, H., Regnier, M., and Murry, C.E. (2016). Mechanical Stress Conditioning and Electrical Stimulation Promote

Contractility and Force Maturation of Induced Pluripotent Stem

Cell-Derived Human Cardiac Tissue. Circulation 134, 1557–1567.

https://doi.org/10.1161/CIRCULATIONAHA.114.014998.

Schuldt, M., Pei, J., Harakalova, M., Dorsch, L.M., Schlossarek, S.,

Mokry, M., Knol, J.C., Pham, T.V., Schelfhorst, T., Piersma, S.R.,

et al. (2021). Proteomic and Functional Studies Reveal Detyrosinated

Tubulin as Treatment Target in Sarcomere Mutation-Induced Hypertrophic Cardiomyopathy. Circ. Heart Fail. 14, e007022. https://doi.

org/10.1161/CIRCHEARTFAILURE.120.007022.

Seeger, T., Shrestha, R., Lam, C.K., Chen, C., McKeithan, W.L., Lau,

E., Wnorowski, A., McMullen, G., Greenhaw, M., Lee, J., et al.

(2019). A Premature Termination Codon Mutation in MYBPC3

Causes Hypertrophic Cardiomyopathy via Chronic Activation of

Nonsense-Mediated Decay. Circulation 139, 799–811. https://

doi.org/10.1161/CIRCULATIONAHA.118.034624.

Somura, F., Izawa, H., Iwase, M., Takeichi, Y., Ishiki, R., Nishizawa,

T., Noda, A., Nagata, K., Yamada, Y., and Yokota, M. (2001).

Reduced myocardial sarcoplasmic reticulum Ca(2+)-ATPase

mRNA expression and biphasic force-frequency relations in patients with hypertrophic cardiomyopathy. Circulation 104, 658–

663. https://doi.org/10.1161/hc3101.093869.

Van Driest, S.L., Ackerman, M.J., Ommen, S.R., Shakur, R., Will,

M.L., Nishimura, R.A., Tajik, A.J., and Gersh, B.J. (2002). Prevalence

and severity of "benign" mutations in the beta-myosin heavy

chain, cardiac troponin T, and alpha-tropomyosin genes in hypertrophic cardiomyopathy. Circulation 106, 3085–3090. https://doi.

org/10.1161/01.cir.0000042675.59901.14.

Yu, G., Wang, L.G., Yan, G.R., and He, Q.Y. (2015). DOSE: an R/Bioconductor package for disease ontology semantic and enrichment

analysis. Bioinformatics 31, 608–609. https://doi.org/10.1093/bioinformatics/btu684.

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