Abstract
The heart’s limited regenerative capacity raises the need for novel stem cell-based therapeutic approaches for cardiac regeneration. However, the use of stem cells is restrictive due to poor determination of their properties and the factors that regulate them. Here, we investigated the role of desmin, the major muscle-specific intermediate filament protein, in the characteristics and differentiation capacity of cardiac side population (CSP) and Sca1+ stem cells of adult mice. We found that desmin deficiency affects the microenvironment of the cells and leads to increased numbers of CSP but not Sca1+ cells; CSP subpopulation composition is altered, the expression of the senescence marker p16INK4a in Sca1+ cells is increased, and early cardiomyogenic commitment is impaired. Specifically, we found that mRNA levels of the cardiac transcription factors Mef2c and Nkx2.5 were significantly reduced in des−/− CSP and Sca1+ cells, while differentiation of CSP and Sca1+ cells demonstrated that in the absence of desmin, the levels of Nkx2.5, Mef2c, Tnnt2, Hey2, and Myh6 mRNA are differentially affected. Thus, desmin deficiency restricts the regenerative potential of CSP and Sca1+ cells, both directly and indirectly through their microenvironment.
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References
Abbott JD, Huang Y, Liu D, Hickey R, Krause DS, Giordano FJ (2004) Stromal cell-derived factor-1alpha plays a critical role in stem cell recruitment to the heart after myocardial infarction but is not sufficient to induce homing in the absence of injury. Circulation 110(21):3300–3305. https://doi.org/10.1161/01.CIR.0000147780.30124.CF
Allen RE, Rankin LL, Greene EA, Boxhorn LK, Johnson SE, Taylor RG, Pierce PR (1991) Desmin is present in proliferating rat muscle satellite cells but not in bovine muscle satellite cells. J Cell Physiol 149(3):525–535. https://doi.org/10.1002/jcp.1041490323
Anderson DJ, Kaplan DI, Bell KM, Koutsis K, Haynes JM, Mills RJ, Phelan DG, Qian EL, Leitoguinho AR, Arasaratnam D, Labonne T, Ng ES, Davis RP, Casini S, Passier R, Hudson JE, Porrello ER, Costa MW, Rafii A, Curl CL, Delbridge LM, Harvey RP, Oshlack A, Cheung MM, Mummery CL, Petrou S, Elefanty AG, Stanley EG, Elliott DA (2018) NKX2-5 regulates human cardiomyogenesis via a HEY2 dependent transcriptional network. Nat Commun 9(1):1373. https://doi.org/10.1038/s41467-018-03714-x
Ansseau E, Eidahl JO, Lancelot C, Tassin A, Matteotti C, Yip C, Liu J, Leroy B, Hubeau C, Gerbaux C, Cloet S, Wauters A, Zorbo S, Meyer P, Pirson I, Laoudj-Chenivesse D, Wattiez R, Harper SQ, Belayew A, Coppée F (2016) Homologous Transcription Factors DUX4 and DUX4c Associate with Cytoplasmic Proteins during Muscle Differentiation. PLoS ONE 11(1):e0146893. https://doi.org/10.1371/journal.pone.0146893
Ara MN, Hyodo M, Ohga N, Akiyama K, Hida K, Hida Y, Shinohara N, Harashima H (2014) Identification and expression of troponin T, a new marker on the surface of cultured tumor endothelial cells by aptamer ligand. Cancer Med 3(4):825–834. https://doi.org/10.1002/cam4.260
Askari AT, Unzek S, Popovic ZB, Goldman CK, Forudi F, Kiedrowski M, Rovner A, Ellis SG, Thomas JD, DiCorleto PE, Topol EJ, Penn MS (2003) Effect of stromal-cell-derived factor 1 on stem-cell homing and tissue regeneration in ischaemic cardiomyopathy. Lancet Lond Engl 362(9385):697–703. https://doi.org/10.1016/S0140-6736(03)14232-8
Ball AJ, Levine F (2005) Telomere-independent cellular senescence in human fetal cardiomyocytes. Aging Cell 4(1):21–30. https://doi.org/10.1111/j.1474-9728.2004.00137.x
Beltrami AP, Barlucchi L, Torella D, Baker M, Limana F, Chimenti S, Kasahara H, Rota M, Musso E, Urbanek K, Leri A, Kajstura J, Nadal-Ginard B, Anversa P (2003) Adult cardiac stem cells are multipotent and support myocardial regeneration. Cell 114(6):763–776. https://doi.org/10.1016/s0092-8674(03)00687-1
Bergmann O, Bhardwaj RD, Bernard S, Zdunek S, Barnabé-Heider F, Walsh S, Zupicich J, Alkass K, Buchholz BA, Druid H, Jovinge S, Frisén J (2009) Evidence for cardiomyocyte renewal in humans. Science 324(5923):98–102. https://doi.org/10.1126/science.1164680
Booth SA, Charchar FJ (2017) Cardiac telomere length in heart development, function, and disease. Physiol Genomics 49(7):368–384. https://doi.org/10.1152/physiolgenomics.00024.2017
Camargo FD, Green R, Capetanaki Y, Jackson KA, Goodell MA, Capetenaki Y (2003) Single hematopoietic stem cells generate skeletal muscle through myeloid intermediates. Nat Med 9(12):1520–1527. https://doi.org/10.1038/nm963
Capetanaki Y, Bloch RJ, Kouloumenta A, Mavroidis M, Psarras S (2007) Muscle intermediate filaments and their links to membranes and membranous organelles. Exp Cell Res 313(10):2063–2076. https://doi.org/10.1016/j.yexcr.2007.03.033
Capetanaki Y, Papathanasiou S, Diokmetzidou A, Vatsellas G, Tsikitis M (2015) Desmin Related Disease: A Matter of Cell Survival Failure. Curr Opin Cell Biol 0:113–120. https://doi.org/10.1016/j.ceb.2015.01.004
Cesselli D, Beltrami AP, D’Aurizio F, Marcon P, Bergamin N, Toffoletto B, Pandolfi M, Puppato E, Marino L, Signore S, Livi U, Verardo R, Piazza S, Marchionni L, Fiorini C, Schneider C, Hosoda T, Rota M, Kajstura J, Anversa P, Beltrami CA, Leri A (2011) Effects of age and heart failure on human cardiac stem cell function. Am J Pathol 179(1):349–366. https://doi.org/10.1016/j.ajpath.2011.03.036
Desjardins CA, Naya FJ (2017) Antagonistic regulation of cell-cycle and differentiation gene programs in neonatal cardiomyocytes by homologous MEF2 transcription factors. J Biol Chem 292(25):10613–10629. https://doi.org/10.1074/jbc.M117.776153
Diokmetzidou A, Soumaka E, Kloukina I, Tsikitis M, Makridakis M, Varela A, Davos CH, Georgopoulos S, Anesti V, Vlahou A, Capetanaki Y (2016a) Desmin and αB-crystallin interplay in the maintenance of mitochondrial homeostasis and cardiomyocyte survival. J Cell Sci 129(20):3705–3720. https://doi.org/10.1242/jcs.192203
Diokmetzidou A, Tsikitis M, Nikouli S, Kloukina I, Tsoupri E, Papathanasiou S, Psarras S, Mavroidis M, Capetanaki Y (2016b) Strategies to Study Desmin in Cardiac Muscle and Culture Systems. Methods Enzymol 568:427–459. https://doi.org/10.1016/bs.mie.2015.09.026
Ellison GM, Vicinanza C, Smith AJ, Aquila I, Leone A, Waring CD, Henning BJ, Stirparo GG, Papait R, Scarfò M, Agosti V, Viglietto G, Condorelli G, Indolfi C, Ottolenghi S, Torella D, Nadal-Ginard B (2013) Adult c-kit(pos) cardiac stem cells are necessary and sufficient for functional cardiac regeneration and repair. Cell 154(4):827–842. https://doi.org/10.1016/j.cell.2013.07.039
Eschenhagen T, Bolli R, Braun T, Field LJ, Fleischmann BK, Frisén J, Giacca M, Hare JM, Houser S, Lee RT, Marbán E, Martin JF, Molkentin JD, Murry CE, Riley PR, Ruiz-Lozano P, Sadek HA, Sussman MA, Hill JA (2017) Cardiomyocyte Regeneration: A Consensus Statement. Circulation 136(7):680–686. https://doi.org/10.1161/CIRCULATIONAHA.117.029343
Fischer A, Schumacher N, Maier M, Sendtner M, Gessler M (2004) The Notch target genes Hey1 and Hey2 are required for embryonic vascular development. Genes Dev 18(8):901–911. https://doi.org/10.1101/gad.291004
Frangogiannis NG (2014) The inflammatory response in myocardial injury, repair, and remodelling. Nat Rev Cardiol 11(5):255–265. https://doi.org/10.1038/nrcardio.2014.28
Fuchs C, Gawlas S, Heher P, Nikouli S, Paar H, Ivankovic M, Schultheis M, Klammer J, Gottschamel T, Capetanaki Y, Weitzer G (2016) Desmin enters the nucleus of cardiac stem cells and modulates Nkx2.5 expression by participating in transcription factor complexes that interact with the nkx2.5 gene. Biol Open 5(2):140–153. https://doi.org/10.1242/bio.014993
Galata Z, Kloukina I, Kostavasili I, Varela A, Davos CH, Makridakis M, Bonne G, Capetanaki Y (2018) Amelioration of desmin network defects by αB-crystallin overexpression confers cardioprotection in a mouse model of dilated cardiomyopathy caused by LMNA gene mutation. J Mol Cell Cardiol 125:73–86. https://doi.org/10.1016/j.yjmcc.2018.10.017
Georgatos SD, Weber K, Geisler N, Blobel G (1987) Binding of two desmin derivatives to the plasma membrane and the nuclear envelope of avian erythrocytes: evidence for a conserved site-specificity in intermediate filament-membrane interactions. Proc Natl Acad Sci U S A 84(19):6780–6784. https://doi.org/10.1073/pnas.84.19.6780
Gibb N, Lazic S, Yuan X, Deshwar AR, Leslie M, Wilson MD, Scott IC (2018) Hey2 regulates the size of the cardiac progenitor pool during vertebrate heart development. Dev Camb Engl 145(22):dev167510. https://doi.org/10.1242/dev.167510
Gorgoulis V, Adams PD, Alimonti A, Bennett DC, Bischof O, Bishop C, Campisi J, Collado M, Evangelou K, Ferbeyre G, Gil J, Hara E, Krizhanovsky V, Jurk D, Maier AB, Narita M, Niedernhofer L, Passos JF, Robbins PD, Schmitt CA, Sedivy J, Vougas K, von Zglinicki T, Zhou D, Serrano M, Demaria M (2019) Cellular Senescence: Defining a Path Forward. Cell 179(4):813–827. https://doi.org/10.1016/j.cell.2019.10.005
Gude NA, Broughton KM, Firouzi F, Sussman MA (2018) Cardiac ageing: extrinsic and intrinsic factors in cellular renewal and senescence. Nat Rev Cardiol 15(9):523–542. https://doi.org/10.1038/s41569-018-0061-5
Heffler J, Shah PP, Robison P, Phyo S, Veliz K, Uchida K, Bogush A, Rhoades J, Jain R, Prosser BL (2020) A Balance Between Intermediate Filaments and Microtubules Maintains Nuclear Architecture in the Cardiomyocyte. Circ Res 126(3):e10–e26. https://doi.org/10.1161/CIRCRESAHA.119.315582
Hierlihy AM, Seale P, Lobe CG, Rudnicki MA, Megeney LA (2002) The post-natal heart contains a myocardial stem cell population. FEBS Lett 530(1–3):239–243. https://doi.org/10.1016/s0014-5793(02)03477-4
Hofner M, Höllrigl A, Puz S, Stary M, Weitzer G (2007) Desmin stimulates differentiation of cardiomyocytes and up-regulation of brachyury and nkx2.5. Differ Res Biol Divers 75(7):605–615. https://doi.org/10.1111/j.1432-0436.2007.00162.x
Höllrigl A, Hofner M, Stary M, Weitzer G (2007) Differentiation of cardiomyocytes requires functional serine residues within the amino-terminal domain of desmin. Differ Res Biol Divers 75(7):616–626. https://doi.org/10.1111/j.1432-0436.2007.00163.x
Kim T, Echeagaray OH, Wang BJ, Casillas A, Broughton KM, Kim B-H, Sussman MA (2018) In situ transcriptome characteristics are lost following culture adaptation of adult cardiac stem cells. Sci Rep 8(1):12060. https://doi.org/10.1038/s41598-018-30551-1
Kretzschmar K, Post Y, Bannier-Hélaouët M, Mattiotti A, Drost J, Basak O, Li VSW, van den Born M, Gunst QD, Versteeg D, Kooijman L, van der Elst S, van Es JH, van Rooij E, van den Hoff MJB, Clevers H (2018) Profiling proliferative cells and their progeny in damaged murine hearts. Proc Natl Acad Sci U S A 115(52):E12245–E12254. https://doi.org/10.1073/pnas.1805829115
Kuisk IR, Li H, Tran D, Capetanaki Y (1996) A single MEF2 site governs desmin transcription in both heart and skeletal muscle during mouse embryogenesis. Dev Biol 174(1):1–13. https://doi.org/10.1006/dbio.1996.0046
Li H, Capetanaki Y (1993) Regulation of the mouse desmin gene: transactivation by MyoD, myogenin, MRF4 and Myf5. Nucleic Acids Res 21(2):335–343. https://doi.org/10.1093/nar/21.2.335
Li H, Choudhary SK, Milner DJ, Munir MI, Kuisk IR, Capetanaki Y (1994) Inhibition of desmin expression blocks myoblast fusion and interferes with the myogenic regulators MyoD and myogenin. J Cell Biol 124(5):827–841
Liang SX, Khachigian LM, Ahmadi Z, Yang M, Liu S, Chong BH (2011) In vitro and in vivo proliferation, differentiation and migration of cardiac endothelial progenitor cells (SCA1+/CD31+ side-population cells). J Thromb Haemost JTH 9(8):1628–1637. https://doi.org/10.1111/j.1538-7836.2011.04375.x
Liang SX, Tan TYL, Gaudry L, Chong B (2010) Differentiation and migration of Sca1+/CD31- cardiac side population cells in a murine myocardial ischemic model. Int J Cardiol 138(1):40–49. https://doi.org/10.1016/j.ijcard.2008.08.032
Lockard VG, Bloom S (1993) Trans-cellular desmin-lamin B intermediate filament network in cardiac myocytes. J Mol Cell Cardiol 25(3):303–309. https://doi.org/10.1006/jmcc.1993.1036
Mavroidis M, Capetanaki Y (2002) Extensive Induction of Important Mediators of Fibrosis and Dystrophic Calcification in Desmin-Deficient Cardiomyopathy. Am J Pathol 160(3):943–952
Milner DJ, Mavroidis M, Weisleder N, Capetanaki Y (2000) Desmin Cytoskeleton Linked to Muscle Mitochondrial Distribution and Respiratory Function. J Cell Biol 150(6):1283–1298
Milner DJ, Taffet GE, Wang X, Pham T, Tamura T, Hartley C, Gerdes AM, Capetanaki Y (1999) The absence of desmin leads to cardiomyocyte hypertrophy and cardiac dilation with compromised systolic function. J Mol Cell Cardiol 31(11):2063–2076. https://doi.org/10.1006/jmcc.1999.1037
Milner DJ, Weitzer G, Tran D, Bradley A, Capetanaki Y (1996) Disruption of muscle architecture and myocardial degeneration in mice lacking desmin. J Cell Biol 134(5):1255–1270. https://doi.org/10.1083/jcb.134.5.1255
Mouquet F, Pfister O, Jain M, Oikonomopoulos A, Ngoy S, Summer R, Fine A, Liao R (2005) Restoration of cardiac progenitor cells after myocardial infarction by self-proliferation and selective homing of bone marrow-derived stem cells. Circ Res 97(11):1090–1092. https://doi.org/10.1161/01.RES.0000194330.66545.f5
Oh H, Bradfute SB, Gallardo TD, Nakamura T, Gaussin V, Mishina Y, Pocius J, Michael LH, Behringer RR, Garry DJ, Entman ML, Schneider MD (2003) Cardiac progenitor cells from adult myocardium: homing, differentiation, and fusion after infarction. Proc Natl Acad Sci U S A 100(21):12313–12318. https://doi.org/10.1073/pnas.2132126100
Ott HC, Matthiesen TS, Brechtken J, Grindle S, Goh S-K, Nelson W, Taylor DA (2007) The adult human heart as a source for stem cells: repair strategies with embryonic-like progenitor cells. Nat Clin Pract Cardiovasc Med 4(Suppl 1):S27-39. https://doi.org/10.1038/ncpcardio0771
Oyama T, Nagai T, Wada H, Naito AT, Matsuura K, Iwanaga K, Takahashi T, Goto M, Mikami Y, Yasuda N, Akazawa H, Uezumi A, Takeda S, Komuro I (2007) Cardiac side population cells have a potential to migrate and differentiate into cardiomyocytes in vitro and in vivo. J Cell Biol 176(3):329–341. https://doi.org/10.1083/jcb.200603014
Pfister O, Mouquet F, Jain M, Summer R, Helmes M, Fine A, Colucci WS, Liao R (2005) CD31- but Not CD31+ cardiac side population cells exhibit functional cardiomyogenic differentiation. Circ Res 97(1):52–61. https://doi.org/10.1161/01.RES.0000173297.53793.fa
Pfister O, Oikonomopoulos A, Sereti K-I, Liao R (2010) Isolation of resident cardiac progenitor cells by Hoechst 33342 staining. Methods Mol Biol Clifton NJ 660:53–63. https://doi.org/10.1007/978-1-60761-705-1_4
Pillai ICL, Li S, Romay M, Lam L, Lu Y, Huang J, Dillard N, Zemanova M, Rubbi L, Wang Y, Lee J, Xia M, Liang O, Xie Y-H, Pellegrini M, Lusis AJ, Deb A (2017) Cardiac Fibroblasts Adopt Osteogenic Fates and Can Be Targeted to Attenuate Pathological Heart Calcification. Cell Stem Cell 20(2):218-232.e5. https://doi.org/10.1016/j.stem.2016.10.005
Psarras S, Beis D, Nikouli S, Tsikitis M, Capetanaki Y (2019) Three in a Box: Understanding Cardiomyocyte, Fibroblast, and Innate Immune Cell Interactions to Orchestrate Cardiac Repair Processes. Front Cardiovasc Med 6:32. https://doi.org/10.3389/fcvm.2019.00032
Psarras S, Mavroidis M, Sanoudou D, Davos CH, Xanthou G, Varela AE, Panoutsakopoulou V, Capetanaki Y (2012) Regulation of adverse remodelling by osteopontin in a genetic heart failure model. Eur Heart J 33(15):1954–1963. https://doi.org/10.1093/eurheartj/ehr119
Qiu Y, Bayomy AF, Gomez MV, Bauer M, Du P, Yang Y, Zhang X, Liao R (2015) A role for matrix stiffness in the regulation of cardiac side population cell function. Am J Physiol Heart Circ Physiol 308(9):H990-997. https://doi.org/10.1152/ajpheart.00935.2014
Sacilotto N, Chouliaras KM, Nikitenko LL, Lu YW, Fritzsche M, Wallace MD, Nornes S, García-Moreno F, Payne S, Bridges E, Liu K, Biggs D, Ratnayaka I, Herbert SP, Molnár Z, Harris AL, Davies B, Bond GL, Bou-Gharios G, Schwarz JJ, De Val S (2016) MEF2 transcription factors are key regulators of sprouting angiogenesis. Genes Dev 30(20):2297–2309. https://doi.org/10.1101/gad.290619.116
Sakellariou D, Chiourea M, Raftopoulou C, Gagos S (2013) Alternative lengthening of telomeres: recurrent cytogenetic aberrations and chromosome stability under extreme telomere dysfunction. Neoplasia N Y N 15(11):1301–1313. https://doi.org/10.1593/neo.131574
Saxena A, Fish JE, White MD, Yu S, Smyth JWP, Shaw RM, DiMaio JM, Srivastava D (2008) Stromal cell-derived factor-1alpha is cardioprotective after myocardial infarction. Circulation 117(17):2224–2231. https://doi.org/10.1161/CIRCULATIONAHA.107.694992
Senyo SE, Steinhauser ML, Pizzimenti CL, Yang VK, Cai L, Wang M, Wu T-D, Guerquin-Kern J-L, Lechene CP, Lee RT (2013) Mammalian heart renewal by pre-existing cardiomyocytes. Nature 493(7432):433–436. https://doi.org/10.1038/nature11682
Shah SB, Davis J, Weisleder N, Kostavassili I, McCulloch AD, Ralston E, Capetanaki Y, Lieber RL (2004) Structural and functional roles of desmin in mouse skeletal muscle during passive deformation. Biophys J 86(5):2993–3008. https://doi.org/10.1016/S0006-3495(04)74349-0
Torella D, Rota M, Nurzynska D, Musso E, Monsen A, Shiraishi I, Zias E, Walsh K, Rosenzweig A, Sussman MA, Urbanek K, Nadal-Ginard B, Kajstura J, Anversa P, Leri A (2004) Cardiac stem cell and myocyte aging, heart failure, and insulin-like growth factor-1 overexpression. Circ Res 94(4):514–524. https://doi.org/10.1161/01.RES.0000117306.10142.50
Vagnozzi RJ, Sargent MA, Lin S-CJ, Palpant NJ, Murry CE, Molkentin JD (2018) Genetic Lineage Tracing of Sca-1+ Cells Reveals Endothelial but Not Myogenic Contribution to the Murine Heart. Circulation 138(25):2931–2939. https://doi.org/10.1161/CIRCULATIONAHA.118.035210
van Berlo JH, Kanisicak O, Maillet M, Vagnozzi RJ, Karch J, Lin S-CJ, Middleton RC, Marbán E, Molkentin JD (2014) c-kit+ cells minimally contribute cardiomyocytes to the heart. Nature 509(7500):337–341. https://doi.org/10.1038/nature13309
Vandervelde S, van Luyn MJA, Tio RA, Harmsen MC (2005) Signaling factors in stem cell-mediated repair of infarcted myocardium. J Mol Cell Cardiol 39(2):363–376. https://doi.org/10.1016/j.yjmcc.2005.05.012
Weitzer G, Milner DJ, Kim JU, Bradley A, Capetanaki Y (1995) Cytoskeletal control of myogenesis: a desmin null mutation blocks the myogenic pathway during embryonic stem cell differentiation. Dev Biol 172(2):422–439. https://doi.org/10.1006/dbio.1995.8070
Wilker PR, Kohyama M, Sandau MM, Albring JC, Nakagawa O, Schwarz JJ, Murphy KM (2008) Transcription factor Mef2c is required for B cell proliferation and survival after antigen receptor stimulation. Nat Immunol 9(6):603–612. https://doi.org/10.1038/ni.1609
Wu Q, Zhan J, Pu S, Qin L, Li Y, Zhou Z (2017) Influence of aging on the activity of mice Sca-1+CD31- cardiac stem cells. Oncotarget 8(1):29–41. https://doi.org/10.18632/oncotarget.13930
Yamahara K, Fukushima S, Coppen SR, Felkin LE, Varela-Carver A, Barton PJR, Yacoub MH, Suzuki K (2008) Heterogeneic nature of adult cardiac side population cells. Biochem Biophys Res Commun 371(4):615–620. https://doi.org/10.1016/j.bbrc.2008.04.021
Yoon J, Choi SC, Park CY, Shim WJ, Lim D-S (2007) Cardiac side population cells exhibit endothelial differentiation potential. Exp Mol Med 39(5):653–662. https://doi.org/10.1038/emm.2007.71
Zhang R, Pan X, Huang Z, Weber GF, Zhang G (2011) Osteopontin enhances the expression and activity of MMP-2 via the SDF-1/CXCR4 axis in hepatocellular carcinoma cell lines. PLoS ONE 6(8):e23831. https://doi.org/10.1371/journal.pone.0023831
Zhang Y, Sivakumaran P, Newcomb AE, Hernandez D, Harris N, Khanabdali R, Liu G-S, Kelly DJ, Pébay A, Hewitt AW, Boyle A, Harvey R, Morrison WA, Elliott DA, Dusting GJ, Lim SY (2015) Cardiac Repair With a Novel Population of Mesenchymal Stem Cells Resident in the Human Heart. Stem Cells Dayt Ohio 33(10):3100–3113. https://doi.org/10.1002/stem.2101
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We thank very much I Kostavasili for her assistance throughout this work
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This research was funded by ESPA 09SYN-21- 966 and ‘’Excellence II’’/ARISTEIA II 5342 grants from the Greek Secretariat (Hellenic Foundation) for R&D and from the BRFAA-Onassis Cardiac Surgery Center Collaboration ΙΩ005 Grant to Y.C.
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This project was conceived by Y.C. and S.N. Experiments were performed by S.N., M.T., and C.R., with constant conceptual and technical assistance by SP. Y.C and S.N. interpreted results and S.G. helped with some data analysis. The original draft manuscript was written by S.N. Y.C. supervised the project and reviewed and edited the manuscript. All authors have read and agreed to the published version of the manuscript.
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Nikouli, S., Tsikitis, M., Raftopoulou, C. et al. Desmin deficiency affects the microenvironment of the cardiac side population and Sca1+ stem cell population of the adult heart and impairs their cardiomyogenic commitment. Cell Tissue Res 389, 309–326 (2022). https://doi.org/10.1007/s00441-022-03643-8
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DOI: https://doi.org/10.1007/s00441-022-03643-8