Induction of cardiomyocyte‑like cells from hair follicle cells in mice

  • Authors:
    • Yong‑Hee Kim
    • Bang‑Jin Kim
    • Seok‑Man Kim
    • Sun‑Uk Kim
    • Buom‑Yong Ryu
  • View Affiliations

  • Published online on: March 13, 2019     https://doi.org/10.3892/ijmm.2019.4133
  • Pages: 2230-2240
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Abstract

Hair follicles (HFs) are a well‑characterized niche for adult stem cells (SCs), and include epithelial and melanocytic SCs. HF cells are an accessible source of multipotent adult SCs for the generation of the interfollicular epidermis, HF structures and sebaceous glands in addition to the reconstitution of novel HFs in vivo. In the present study, it was demonstrated that HF cells are able to be induced to differentiate into cardiomyocyte‑like cells in vitro under specific conditions. It was determined that HF cells cultured on OP9 feeder cells in KnockOut‑Dulbecco's modified Eagle's medium/B27 in the presence of vascular endothelial growth factors differentiated into cardiomyocyte‑like cells that express markers specific to cardiac lineage, but do not express non‑cardiac lineage markers including neural stem/progenitor cell, HF bulge cells or undifferentiated spermatogonia markers. These cardiomyocyte‑like cells exhibited a spindle‑ and filament‑shaped morphology similar to that presented by cardiac muscles and exhibited spontaneous beating that persisted for over 3 months. These results demonstrate that SC reprogramming and differentiation may be induced without resulting in any genetic modification, which is important for the clinical applications of SCs including tissue and organ regeneration.

References

1 

Mortality GBD and Causes of Death C: Global, regional, and national life expectancy, all-cause mortality, and cause-specific mortality for 249 causes of death, 1980-2015: a systematic analysis for the Global Burden of Disease Study 2015. Lancet. 388:1459–1544. 2016. View Article : Google Scholar

2 

Weir RA and McMurray JJ: Epidemiology of heart failure and left ventricular dysfunction after acute myocardial infarction. Curr Heart Fail Rep. 3:175–180. 2006. View Article : Google Scholar : PubMed/NCBI

3 

Roger VL, Go AS, Lloyd-Jones DM, Benjamin EJ, Berry JD, Borden WB, Bravata DM, Dai S, Ford ES, Fox CS, et al American Heart Association Statistics Committee and Stroke Statistics Subcommittee: Heart disease and stroke statistics–2012 update: A report from the American Heart Association. Circulation. 125:e2–220. 2012.

4 

Thygesen K, Alpert JS and White HD: Joint ESC/ACCF/ AHA/WHF Task Force for the redefinition of myocardial infarction: Universal definition of myocardial infarction. J Am Coll Cardiol. 50:2173–2195. 2007. View Article : Google Scholar : PubMed/NCBI

5 

Hunter JJ and Chien KR: Signaling pathways for cardiac hypertrophy and failure. N Engl J Med. 341:1276–1283. 1999. View Article : Google Scholar : PubMed/NCBI

6 

Beaglehole R, Bonita R, Horton R, Adams O and McKee M: Public health in the new era: Improving health through collective action. Lancet. 363:2084–2086. 2004. View Article : Google Scholar : PubMed/NCBI

7 

Dubois NC, Craft AM, Sharma P, Elliott DA, Stanley EG, Elefanty AG, Gramolini A and Keller G: SIRPA is a specific cell-surface marker for isolating cardiomyocytes derived from human pluripotent stem cells. Nat Biotechnol. 29:1011–1018. 2011. View Article : Google Scholar : PubMed/NCBI

8 

Fijnvandraat AC, van Ginneken AC, de Boer PA, Ruijter JM, Christoffels VM, Moorman AF and Lekanne Deprez RH: Cardiomyocytes derived from embryonic stem cells resemble cardiomyocytes of the embryonic heart tube. Cardiovasc Res. 58:399–409. 2003. View Article : Google Scholar : PubMed/NCBI

9 

Hidaka K, Lee JK, Kim HS, Ihm CH, Iio A, Ogawa M, Nishikawa S, Kodama I and Morisaki T: Chamber-specific differentiation of Nkx2.5-positive cardiac precursor cells from murine embryonic stem cells. FASEB J. 17:740–742. 2003. View Article : Google Scholar : PubMed/NCBI

10 

Hattori F, Chen H, Yamashita H, Tohyama S, Satoh YS, Yuasa S, Li W, Yamakawa H, Tanaka T, Onitsuka T, et al: Nongenetic method for purifying stem cell-derived cardiomyocytes. Nat Methods. 7:61–66. 2010. View Article : Google Scholar

11 

Baba S, Heike T, Yoshimoto M, Umeda K, Doi H, Iwasa T, Lin X, Matsuoka S, Komeda M and Nakahata T: Flk1(+) cardiac stem/progenitor cells derived from embryonic stem cells improve cardiac function in a dilated cardiomyopathy mouse model. Cardiovasc Res. 76:119–131. 2007. View Article : Google Scholar : PubMed/NCBI

12 

Guan K, Wagner S, Unsöld B, Maier LS, Kaiser D, Hemmerlein B, Nayernia K, Engel W and Hasenfuss G: Generation of functional cardiomyocytes from adult mouse spermatogonial stem cells. Circ Res. 100:1615–1625. 2007. View Article : Google Scholar : PubMed/NCBI

13 

Wang IN, Wang X, Ge X, Anderson J, Ho M, Ashley E, Liu J, Butte MJ, Yazawa M, Dolmetsch RE, et al: Apelin enhances directed cardiac differentiation of mouse and human embryonic stem cells. PLoS One. 7:e383282012. View Article : Google Scholar : PubMed/NCBI

14 

Zhu WZ, Hauch KD, Xu C and Laflamme MA: Human embryonic stem cells and cardiac repair. Transplant Rev (Orlando). 23:53–68. 2009. View Article : Google Scholar

15 

Klaus A, Saga Y, Taketo MM, Tzahor E and Birchmeier W: Distinct roles of Wnt/beta-catenin and Bmp signaling during early cardiogenesis. Proc Natl Acad Sci USA. 104:18531–18536. 2007. View Article : Google Scholar : PubMed/NCBI

16 

Taha MF and Valojerdi MR: Effect of bone morphogenetic protein-4 on cardiac differentiation from mouse embryonic stem cells in serum-free and low-serum media. Int J Cardiol. 127:78–87. 2008. View Article : Google Scholar

17 

Ladd AN, Yatskievych TA and Antin PB: Regulation of avian cardiac myogenesis by activin/TGFbeta and bone morphogenetic proteins. Dev Biol. 204:407–419. 1998. View Article : Google Scholar

18 

Hoffman RM: The hair follicle as a gene therapy target. Nat Biotechnol. 18:20–21. 2000. View Article : Google Scholar : PubMed/NCBI

19 

Oshima H, Rochat A, Kedzia C, Kobayashi K and Barrandon Y: Morphogenesis and renewal of hair follicles from adult multi-potent stem cells. Cell. 104:233–245. 2001. View Article : Google Scholar : PubMed/NCBI

20 

Cotsarelis G, Sun TT and Lavker RM: Label-retaining cells reside in the bulge area of pilosebaceous unit: Implications for follicular stem cells, hair cycle, and skin carcinogenesis. Cell. 61:1329–1337. 1990. View Article : Google Scholar : PubMed/NCBI

21 

Morris RJ and Potten CS: Highly persistent label-retaining cells in the hair follicles of mice and their fate following induction of anagen. J Invest Dermatol. 112:470–475. 1999. View Article : Google Scholar : PubMed/NCBI

22 

Taylor G, Lehrer MS, Jensen PJ, Sun TT and Lavker RM: Involvement of follicular stem cells in forming not only the follicle but also the epidermis. Cell. 102:451–461. 2000. View Article : Google Scholar : PubMed/NCBI

23 

Tumbar T, Guasch G, Greco V, Blanpain C, Lowry WE, Rendl M and Fuchs E: Defining the epithelial stem cell niche in skin. Science. 303:359–363. 2004. View Article : Google Scholar

24 

Toma JG, Akhavan M, Fernandes KJ, Barnabé-Heider F, Sadikot A, Kaplan DR and Miller FD: Isolation of multipotent adult stem cells from the dermis of mammalian skin. Nat Cell Biol. 3:778–784. 2001. View Article : Google Scholar : PubMed/NCBI

25 

Fernandes KJ, McKenzie IA, Mill P, Smith KM, Akhavan M, Barnabé-Heider F, Biernaskie J, Junek A, Kobayashi NR, Toma JG, et al: A dermal niche for multipotent adult skin-derived precursor cells. Nat Cell Biol. 6:1082–1093. 2004. View Article : Google Scholar : PubMed/NCBI

26 

Sieber-Blum M, Grim M, Hu YF and Szeder V: Pluripotent neural crest stem cells in the adult hair follicle. Dev Dyn. 231:258–269. 2004. View Article : Google Scholar : PubMed/NCBI

27 

Li L, Mignone J, Yang M, Matic M, Penman S, Enikolopov G and Hoffman RM: Nestin expression in hair follicle sheath progenitor cells. Proc Natl Acad Sci USA. 100:9958–9961. 2003. View Article : Google Scholar : PubMed/NCBI

28 

Yano K, Brown LF and Detmar M: Control of hair growth and follicle size by VEGF-mediated angiogenesis. J Clin Invest. 107:409–417. 2001. View Article : Google Scholar : PubMed/NCBI

29 

Mecklenburg L, Tobin DJ, Müller-Röver S, Handjiski B, Wendt G, Peters EM, Pohl S, Moll I and Paus R: Active hair growth (anagen) is associated with angiogenesis. J Invest Dermatol. 114:909–916. 2000. View Article : Google Scholar : PubMed/NCBI

30 

Amoh Y, Li L, Yang M, Moossa AR, Katsuoka K, Penman S and Hoffman RM: Nascent blood vessels in the skin arise from nestin-expressing hair-follicle cells. Proc Natl Acad Sci USA. 101:13291–13295. 2004. View Article : Google Scholar : PubMed/NCBI

31 

Amoh Y, Li L, Katsuoka K, Penman S and Hoffman RM: Multipotent nestin-positive, keratin-negative hair-follicle bulge stem cells can form neurons. Proc Natl Acad Sci USA. 102:5530–5534. 2005. View Article : Google Scholar : PubMed/NCBI

32 

Yashiro M, Mii S, Aki R, Hamada Y, Arakawa N, Kawahara K, Hoffman RM and Amoh Y: From hair to heart: Nestin-expressing hair-follicle-associated pluripotent (HAP) stem cells differentiate to beating cardiac muscle cells. Cell Cycle. 14:2362–2366. 2015. View Article : Google Scholar : PubMed/NCBI

33 

National Research Council (US) Committee for the Update of the Guide for the Care and Use of Laboratory Animals: Guide for the Care and Use of Laboratory Animals. 8th edition. National Academies Press (US); Washington, DC: 2011

34 

Nath M, Offers M, Hummel M and Seissler J: Isolation and in vitro expansion of Lgr6-positive multipotent hair follicle stem cells. Cell Tissue Res. 344:435–444. 2011. View Article : Google Scholar : PubMed/NCBI

35 

Kubota H, Avarbock MR and Brinster RL: Growth factors essential for self-renewal and expansion of mouse spermatogonial stem cells. Proc Natl Acad Sci USA. 101:16489–16494. 2004. View Article : Google Scholar : PubMed/NCBI

36 

Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods. 25:402–408. 2001. View Article : Google Scholar

37 

Fox V, Gokhale PJ, Walsh JR, Matin M, Jones M and Andrews PW: Cell-cell signaling through NOTCH regulates human embryonic stem cell proliferation. Stem Cells. 26:715–723. 2008. View Article : Google Scholar

38 

Kattman SJ, Huber TL and Keller GM: Multipotent flk-1+ cardiovascular progenitor cells give rise to the cardiomyocyte, endothelial, and vascular smooth muscle lineages. Dev Cell. 11:723–732. 2006. View Article : Google Scholar : PubMed/NCBI

39 

Jang J, Ku SY, Kim JE, Choi K, Kim YY, Kim HS, Oh SK, Lee EJ, Cho HJ, Song YH, et al: Notch inhibition promotes human embryonic stem cell-derived cardiac mesoderm differentiation. Stem Cells. 26:2782–2790. 2008. View Article : Google Scholar : PubMed/NCBI

40 

Noggle SA, Weiler D and Condie BG: Notch signaling is inactive but inducible in human embryonic stem cells. Stem Cells. 24:1646–1653. 2006. View Article : Google Scholar : PubMed/NCBI

41 

Kattman SJ, Witty AD, Gagliardi M, Dubois NC, Niapour M, Hotta A, Ellis J and Keller G: Stage-specific optimization of activin/nodal and BMP signaling promotes cardiac differentiation of mouse and human pluripotent stem cell lines. Cell Stem Cell. 8:228–240. 2011. View Article : Google Scholar : PubMed/NCBI

42 

Yuasa S, Itabashi Y, Koshimizu U, Tanaka T, Sugimura K, Kinoshita M, Hattori F, Fukami S, Shimazaki T, Ogawa S, et al: Transient inhibition of BMP signaling by Noggin induces cardio-myocyte differentiation of mouse embryonic stem cells. Nat Biotechnol. 23:607–611. 2005. View Article : Google Scholar : PubMed/NCBI

43 

Kim BJ, Kim YH, Lee YA, Jung SE, Hong YH, Lee EJ, Kim BG, Hwang S, Do JT, Pang MG, et al: Platelet-derived growth factor receptor-alpha positive cardiac progenitor cells derived from multipotent germline stem cells are capable of cardiomyogenesis in vitro and in vivo. Oncotarget. 8:29643–29656. 2017.PubMed/NCBI

44 

Org T, Duan D, Ferrari R, Montel-Hagen A, Van Handel B, Kerényi MA, Sasidharan R, Rubbi L, Fujiwara Y, Pellegrini M, et al: Scl binds to primed enhancers in mesoderm to regulate hematopoietic and cardiac fate divergence. EMBO J. 34:759–777. 2015. View Article : Google Scholar : PubMed/NCBI

45 

Bai F, Ho Lim C, Jia J, Santostefano K, Simmons C, Kasahara H, Wu W, Terada N and Jin S: Directed differentiation of embryonic stem cells into cardiomyocytes by bacterial injection of defined transcription factors. Sci Rep. 5:150142015. View Article : Google Scholar : PubMed/NCBI

46 

Li G, Plonowska K, Kuppusamy R, Sturzu A and Wu SM: Identification of cardiovascular lineage descendants at single-cell resolution. Development. 142:846–857. 2015. View Article : Google Scholar : PubMed/NCBI

47 

Eng G, Lee BW, Protas L, Gagliardi M, Brown K, Kass RS, Keller G, Robinson RB and Vunjak-Novakovic G: Autonomous beating rate adaptation in human stem cell-derived cardio-myocytes. Nat Commun. 7:103122016. View Article : Google Scholar

48 

Radaszkiewicz KA, Sýkorová D, Karas P, Kudová J, Kohút L, Binó L, Večeřa J, Víteček J, Kubala L and Pacherník J: Simple non-invasive analysis of embryonic stem cell-derived cardio-myocytes beating in vitro. Rev Sci Instrum. 87:0243012016. View Article : Google Scholar

49 

Hayashi K, Ohta H, Kurimoto K, Aramaki S and Saitou M: Reconstitution of the mouse germ cell specification pathway in culture by pluripotent stem cells. Cell. 146:519–532. 2011. View Article : Google Scholar : PubMed/NCBI

50 

Hayashi K, Ogushi S, Kurimoto K, Shimamoto S, Ohta H and Saitou M: Offspring from oocytes derived from in vitro primordial germ cell-like cells in mice. Science. 338:971–975. 2012. View Article : Google Scholar : PubMed/NCBI

51 

Baba S, Heike T, Umeda K, Iwasa T, Kaichi S, Hiraumi Y, Doi H, Yoshimoto M, Kanatsu-Shinohara M, Shinohara T, et al: Generation of cardiac and endothelial cells from neonatal mouse testis-derived multipotent germline stem cells. Stem Cells. 25:1375–1383. 2007. View Article : Google Scholar : PubMed/NCBI

52 

Yao S, Chen S, Clark J, Hao E, Beattie GM, Hayek A and Ding S: Long-term self-renewal and directed differentiation of human embryonic stem cells in chemically defined conditions. Proc Natl Acad Sci USA. 103:6907–6912. 2006. View Article : Google Scholar : PubMed/NCBI

53 

Ryu BY, Kubota H, Avarbock MR and Brinster RL: Conservation of spermatogonial stem cell self-renewal signaling between mouse and rat. Proc Natl Acad Sci USA. 102:14302–14307. 2005. View Article : Google Scholar : PubMed/NCBI

54 

Conlon FL, Lyons KM, Takaesu N, Barth KS, Kispert A, Herrmann B and Robertson EJ: A primary requirement for nodal in the formation and maintenance of the primitive streak in the mouse. Development. 120:1919–1928. 1994.PubMed/NCBI

55 

Gadue P, Huber TL, Paddison PJ and Keller GM: Wnt and TGF-beta signaling are required for the induction of an in vitro model of primitive streak formation using embryonic stem cells. Proc Natl Acad Sci USA. 103:16806–16811. 2006. View Article : Google Scholar : PubMed/NCBI

56 

Liu Y, Asakura M, Inoue H, Nakamura T, Sano M, Niu Z, Chen M, Schwartz RJ and Schneider MD: Sox17 is essential for the specification of cardiac mesoderm in embryonic stem cells. Proc Natl Acad Sci USA. 104:3859–3864. 2007. View Article : Google Scholar : PubMed/NCBI

57 

Marvin MJ, Di Rocco G, Gardiner A, Bush SM and Lassar AB: Inhibition of Wnt activity induces heart formation from posterior mesoderm. Genes Dev. 15:316–327. 2001. View Article : Google Scholar : PubMed/NCBI

58 

Schneider VA and Mercola M: Wnt antagonism initiates cardio-genesis in Xenopus laevis. Genes Dev. 15:304–315. 2001. View Article : Google Scholar : PubMed/NCBI

59 

Schultheiss TM, Burch JB and Lassar AB: A role for bone morphogenetic proteins in the induction of cardiac myogenesis. Genes Dev. 11:451–462. 1997. View Article : Google Scholar : PubMed/NCBI

60 

Tzahor E and Lassar AB: Wnt signals from the neural tube block ectopic cardiogenesis. Genes Dev. 15:255–260. 2001. View Article : Google Scholar : PubMed/NCBI

61 

Yatskievych TA, Ladd AN and Antin PB: Induction of cardiac myogenesis in avian pregastrula epiblast: The role of the hypoblast and activin. Development. 124:2561–2570. 1997.PubMed/NCBI

62 

Iida M, Heike T, Yoshimoto M, Baba S, Doi H and Nakahata T: Identification of cardiac stem cells with FLK1, CD31, and VE-cadherin expression during embryonic stem cell differentiation. FASEB J. 19:371–378. 2005. View Article : Google Scholar : PubMed/NCBI

63 

Murakami Y, Hirata H, Miyamoto Y, Nagahashi A, Sawa Y, Jakt M, Asahara T and Kawamata S: Isolation of cardiac cells from E8.5 yolk sac by ALCAM (CD166) expression. Mech Dev. 124:830–839. 2007. View Article : Google Scholar : PubMed/NCBI

64 

Misfeldt AM, Boyle SC, Tompkins KL, Bautch VL, Labosky PA and Baldwin HS: Endocardial cells are a distinct endothelial lineage derived from Flk1+ multipotent cardiovascular progenitors. Dev Biol. 333:78–89. 2009. View Article : Google Scholar : PubMed/NCBI

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May 2019
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APA
Kim, Y., Kim, B., Kim, S., Kim, S., & Ryu, B. (2019). Induction of cardiomyocyte‑like cells from hair follicle cells in mice. International Journal of Molecular Medicine, 43, 2230-2240. https://doi.org/10.3892/ijmm.2019.4133
MLA
Kim, Y., Kim, B., Kim, S., Kim, S., Ryu, B."Induction of cardiomyocyte‑like cells from hair follicle cells in mice". International Journal of Molecular Medicine 43.5 (2019): 2230-2240.
Chicago
Kim, Y., Kim, B., Kim, S., Kim, S., Ryu, B."Induction of cardiomyocyte‑like cells from hair follicle cells in mice". International Journal of Molecular Medicine 43, no. 5 (2019): 2230-2240. https://doi.org/10.3892/ijmm.2019.4133