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Generation and characterization of hair-bearing skin organoids from human pluripotent stem cells

Nature Protocols volume 17, pages 1266–1305 (2022)Cite this article

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Abstract

Human skin uses millions of hairs and glands distributed across the body surface to function as an external barrier, thermoregulator and stimuli sensor. The large-scale generation of human skin with these appendages would be beneficial, but is challenging. Here, we describe a detailed protocol for generating hair-bearing skin tissue entirely from a homogeneous population of human pluripotent stem cells in a three-dimensional in vitro culture system. Defined culture conditions are used over a 2-week period to induce differentiation of pluripotent stem cells to surface ectoderm and cranial neural crest cells, which give rise to the epidermis and dermis, respectively, in each organoid unit. After 60 d of incubation, the skin organoids produce hair follicles. By day ~130, the skin organoids reach full complexity and contain stratified skin layers, pigmented hair follicles, sebaceous glands, Merkel cells and sensory neurons, recapitulating the cell composition and architecture of fetal skin tissue at week 18 of gestation. Skin organoids can be maintained in culture using this protocol for up to 150 d, enabling the organoids to be used to investigate basic skin biology, model disease and, further, reconstruct or regenerate skin tissue.

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Fig. 1: Schematics comparing in vivo and in vitro skin organogenesis.
Fig. 2: Illustration of day-by-day differentiation protocol and representative checkpoint images.
Fig. 3: Images from optimal timepoints to check differentiation and characterization of the resulting skin organoids structure.
Fig. 4: qCe3D whole-mount immunostaining.
Fig. 5: Morphologies of developing skin organoids during differentiation.
Fig. 6: Morphological differences of skin organoids incubated with differing BMP4 concentrations.
Fig. 7: Representative phase-contrast images of recommended cell seeding density and cell confluency.

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References

  1. Dąbrowska, A. K. et al. The relationship between skin function, barrier properties, and body‐dependent factors. Ski. Res. Technol. 24, 165–174 (2018).

    Article  Google Scholar 

  2. Kolarsick, P. A. J., Kolarsick, M. A. & Goodwin, C. Anatomy and physiology of the skin. J. Dermatol. Nurs. Assoc. 3, 203–213 (2011).

    Google Scholar 

  3. Nose, H., Kamijo, Y. & Masuki, S. Chapter 25—interactions between body fluid homeostasis and thermoregulation in humans. Handb. Clin. Neurol. 156, 417–429 (2018).

    Article  PubMed  Google Scholar 

  4. Woo, S.-H., Lumpkin, E. A. & Patapoutian, A. Merkel cells and neurons keep in touch. Trends Cell Biol. 25, 74–81 (2015).

    Article  PubMed  Google Scholar 

  5. Zimmerman, A., Bai, L. & Ginty, D. D. The gentle touch receptors of mammalian skin. Science 346, 950–954 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Sun, B. K., Siprashvili, Z. & Khavari, P. A. Advances in skin grafting and treatment of cutaneous wounds. Science 346, 941–945 (2014).

    Article  CAS  PubMed  Google Scholar 

  7. Karimkhani, C. et al. Global skin disease morbidity and mortality: an update from the Global Burden of Disease Study 2013. JAMA Dermatol. 153, 406–412 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  8. He, Z. et al. Factors affecting health-related quality of life in patients with skin disease: cross-sectional results from 8,789 patients with 16 skin diseases. Health Qual. Life Outcomes 18, 298 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  9. Laughter, M. R. et al. The burden of skin and subcutaneous diseases in the United States from 1990 to 2017. JAMA Dermatol. 156, 874–881 (2020).

    Article  PubMed  Google Scholar 

  10. Laughter, M. R. et al. The global burden of atopic dermatitis: lessons from the Global Burden of Disease Study 1990–2017*. Brit. J. Dermatol. 184, 304–309 (2021).

    Article  CAS  Google Scholar 

  11. Mehrmal, S., Uppal, P., Nedley, N., Giesey, R. L. & Delost, G. R. The global, regional, and national burden of psoriasis in 195 countries and territories, 1990 to 2017: a systematic analysis from the Global Burden of Disease Study 2017. J. Am. Acad. Dermatol. 84, 46–52 (2021).

    Article  PubMed  Google Scholar 

  12. Wu, X., Scott, L., Washenik, K. & Stenn, K. Full-thickness skin with mature hair follicles generated from tissue culture expanded human cells. Tissue Eng. 20, 3314–3321 (2014).

    Article  Google Scholar 

  13. Klicznik, M. M. et al. A novel humanized mouse model to study the function of human cutaneous memory T cells in vivo in human skin. Sci. Rep. 10, 11164 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Agarwal, Y. et al. Development of humanized mouse and rat models with full-thickness human skin and autologous immune cells. Sci. Rep. 10, 14598 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Salgado, G., Ng, Y. Z., Koh, L. F., Goh, C. S. M. & Common, J. E. Human reconstructed skin xenografts on mice to model skin physiology. Differentiation 98, 14–24 (2017).

    Article  CAS  PubMed  Google Scholar 

  16. Takagi, R. et al. Bioengineering a 3D integumentary organ system from iPS cells using an in vivo transplantation model. Sci. Adv. 2, e1500887 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  17. Zheng, Y. et al. Organogenesis from dissociated cells: generation of mature cycling hair follicles from skin-derived cells. J. Invest. Dermatol. 124, 867–876 (2005).

    Article  CAS  PubMed  Google Scholar 

  18. Zomer, H. D. & Trentin, A. G. Skin wound healing in humans and mice: challenges in translational research. J. Dermatol. Sci. 90, 3–12 (2018).

    Article  PubMed  Google Scholar 

  19. Itoh, M. et al. Generation of 3D skin equivalents fully reconstituted from human induced pluripotent stem cells (iPSCs). PLoS ONE 8, e77673 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Yang, R. et al. Generation of folliculogenic human epithelial stem cells from induced pluripotent stem cells. Nat. Commun. 5, 3071–3071 (2014).

    Article  PubMed  Google Scholar 

  21. Gledhill, K. et al. Melanin transfer in human 3D skin equivalents generated exclusively from induced pluripotent stem cells. PLoS ONE 10, e0136713 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  22. Abaci, H. E. et al. Tissue engineering of human hair follicles using a biomimetic developmental approach. Nat. Commun. 9, 5301 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Letsiou, S. Tracing skin aging process: a mini-review of in vitro approaches. Biogerontology 22, 261–272 (2021).

    Article  PubMed  Google Scholar 

  24. Christian, H., Hans & Yves, P. in Skin Disease Models In Vitro and Inflammatory Mechanisms: Predictability for Drug Development 187– 218 (Springer International Publishing, 2021); https://doi.org/10.1007/164_2020_428

  25. Lee, J. et al. Hair-bearing human skin generated entirely from pluripotent stem cells. Nature 582, 399–404 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Lee, J. & Koehler, K. R. Skin organoids: a new human model for developmental and translational research. Exp. Dermatol. 30, 613–620 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  27. Biggs, L. C., Kim, C. S., Miroshnikova, Y. A. & Wickström, S. A. Mechanical forces in the skin: roles in tissue architecture, stability, and function. J. Invest. Dermatol. 140, 284–290 (2019).

    Article  PubMed  Google Scholar 

  28. Wong, R., Geyer, S., Weninger, W., Guimberteau, J. & Wong, J. K. The dynamic anatomy and patterning of skin. Exp. Dermatol. 25, 92–98 (2016).

    Article  PubMed  Google Scholar 

  29. Lee, J. et al. Hair follicle development in mouse pluripotent stem cell-derived skin organoids. Cell Rep. 22, 242–254 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Koehler, K. R., Mikosz, A. M., Molosh, A. I., Patel, D. & Hashino, E. Generation of inner ear sensory epithelia from pluripotent stem cells in 3D culture. Nature 500, 217–221 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Eiraku, M. et al. Self-organized formation of polarized cortical tissues from ESCs and its active manipulation by extrinsic signals. Cell Stem Cell 3, 519–532 (2008).

    Article  CAS  PubMed  Google Scholar 

  32. Eiraku, M. et al. Self-organizing optic-cup morphogenesis in three-dimensional culture. Nature 472, 51–56 (2011).

    Article  CAS  PubMed  Google Scholar 

  33. Koehler, K. R. et al. Generation of inner ear organoids containing functional hair cells from human pluripotent stem cells. Nat. Biotechnol. 35, 583–589 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Prummel, K. D., Nieuwenhuize, S. & Mosimann, C. The lateral plate mesoderm. Development 147, dev175059 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Guibentif, C. et al. Diverse routes toward early somites in the mouse embryo. Dev. Cell 56, 141–153.e6 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Wilson, P. A. & Hemmati-Brivanlou, A. Induction of epidermis and inhibition of neural fate by Bmp-4. Nature 376, 331–333 (1995).

    Article  CAS  PubMed  Google Scholar 

  37. Duverger, O. & Morasso, M. I. To grow or not to grow: hair morphogenesis and human genetic hair disorders. Semin. Cell Dev. Biol. 25, 22–33 (2014).

    Article  PubMed  Google Scholar 

  38. McCune, J. M. & Weissman, I. L. The ban on US government funding research using human fetal tissues: how does this fit with the NIH mission to advance medical science for the benefit of the citizenry? Stem Cell Rep. 13, 777–786 (2019).

    Article  Google Scholar 

  39. Haniffa, M. et al. A roadmap for the Human Developmental Cell Atlas. Nature 597, 196–205 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Yu, Q. et al. Charting human development using a multi-endodermal organ atlas and organoid models. Cell 184, 3281–3298 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Haniffa, M. et al. Human Developmental Cell Atlas: milestones achieved and the roadmap ahead. https://doi.org/10.21203/rs.3.rs-73986/v1 (2020).

  42. Regev, A. et al. The Human Cell Atlas. eLife 6, e27041 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  43. Yucha, S. E. V., Tamamoto, K. A., Nguyen, H., Cairns, D. M. & Kaplan, D. L. Human skin equivalents demonstrate need for neuro-immuno-cutaneous system. Adv. Biosyst. 3, 1800283 (2019).

    Article  Google Scholar 

  44. Meltzer, S., Santiago, C., Sharma, N. & Ginty, D. D. The cellular and molecular basis of somatosensory neuron development. Neuron 109, 3736–3757 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Andersen, J. et al. Generation of functional human 3D cortico-motor assembloids. Cell 183, 1913–1929.e26 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Wainger, B. J. et al. Modeling pain in vitro using nociceptor neurons reprogrammed from fibroblasts. Nat. Neurosci. 18, 17–24 (2015).

    Article  CAS  PubMed  Google Scholar 

  47. Oulès, B. et al. Contribution of GATA6 to homeostasis of the human upper pilosebaceous unit and acne pathogenesis. Nat. Commun. 11, 5067 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  48. Kanwar, I. L. et al. Models for acne: a comprehensive study. Drug Discov. Ther. 12, 329–340 (2018).

    Article  CAS  PubMed  Google Scholar 

  49. Langan, S. M., Irvine, A. D. & Weidinger, S. Atopic dermatitis. Lancet 396, 345–360 (2020).

    Article  CAS  PubMed  Google Scholar 

  50. Condorelli, A. G., Dellambra, E., Logli, E., Zambruno, G. & Castiglia, D. Epidermolysis bullosa-associated squamous cell carcinoma: from pathogenesis to therapeutic perspectives. Int J. Mol. Sci. 20, 5707 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Kim, D. P., Kus, K. J. B. & Ruiz, E. Basal cell carcinoma review. Hematol. Oncol. Clin. North Am. 33, 13–24 (2019).

    Article  PubMed  Google Scholar 

  52. Davis, L. E., Shalin, S. C. & Tackett, A. J. Current state of melanoma diagnosis and treatment. Cancer Biol. Ther. 20, 1–14 (2019).

    Article  Google Scholar 

  53. Que, S. K. T., Zwald, F. O. & Schmults, C. D. Cutaneous squamous cell carcinoma Incidence, risk factors, diagnosis, and staging. J. Am. Acad. Dermatol. 78, 237–247 (2018).

    Article  PubMed  Google Scholar 

  54. Waldman, A. & Schmults, C. Cutaneous squamous cell carcinoma. Hematol. Oncol. Clin. North Am. 33, 1–12 (2019).

    Article  PubMed  Google Scholar 

  55. Hogue, L. & Harvey, V. M. Basal cell carcinoma, squamous cell carcinoma, and cutaneous melanoma in skin of color patients. Dermatol. Clin. 37, 519–526 (2019).

    Article  CAS  PubMed  Google Scholar 

  56. Yum, M. K. et al. Tracing oncogene-driven remodelling of the intestinal stem cell niche. Nature 594, 442–447 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Yang, L., Mali, P., Kim-Kiselak, C. & Church, G. In Gene Correction. Methods in Molecular Biology (Methods and Protocols) (ed. Storici F.) Vol 1114, 245–267 (Humana Press, 2014); https://doi.org/10.1007/978-1-62703-761-7_16

  58. Hendriks, D., Clevers, H. & Artegiani, B. CRISPR-Cas tools and their application in genetic engineering of human stem cells and organoids. Cell Stem Cell 27, 705–731 (2020).

    Article  CAS  PubMed  Google Scholar 

  59. Wenzel, D. et al. Genetically corrected iPSCs as cell therapy for recessive dystrophic epidermolysis bullosa. Sci. Transl. Med. 6, 264ra165–264ra165 (2014).

    Article  PubMed  Google Scholar 

  60. Sebastiano, V. et al. Human COL7A1-corrected induced pluripotent stem cells for the treatment of recessive dystrophic epidermolysis bullosa. Sci. Transl. Med. 6, 264ra163–264ra163 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  61. Tolar, J. et al. Induced pluripotent stem cells from individuals with recessive dystrophic epidermolysis bullosa. J. Invest. Dermatol. 131, 848–856 (2011).

    Article  CAS  PubMed  Google Scholar 

  62. Itoh, M., Kiuru, M., Cairo, M. S. & Christiano, A. M. Generation of keratinocytes from normal and recessive dystrophic epidermolysis bullosa-induced pluripotent stem cells. Proc. Natl Acad. Sci. USA. 108, 8797–8802 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Candi, E., Schmidt, R. & Melino, G. The cornified envelope: a model of cell death in the skin. Nat. Rev. Mol. Cell Biol. 6, 328–340 (2005).

    Article  CAS  PubMed  Google Scholar 

  64. Langbein, L., Yoshida, H., Praetzel-Wunder, S., Parry, D. A. & Schweizer, J. The keratins of the human beard hair medulla: the riddle in the middle. J. Invest. Dermatol. 130, 55–73 (2010).

    Article  CAS  PubMed  Google Scholar 

  65. Lu, C. & Fuchs, E. Sweat gland progenitors in development, homeostasis, and wound repair. Cold Spring Harb. Perspect. Med. 4, a015222 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  66. Lu, C. P., Polak, L., Keyes, B. E. & Fuchs, E. Spatiotemporal antagonism in mesenchymal–epithelial signaling in sweat versus hair fate decision. Science 354, aah6102 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  67. Zhao, X. et al. Review on the vascularization of organoids and organoids-on-a-chip. Front. Bioeng. Biotechnol. 9, 637048 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  68. Augustin, H. G., Koh, G. Y., Thurston, G. & Alitalo, K. Control of vascular morphogenesis and homeostasis through the angiopoietin–Tie system. Nat. Rev. Mol. Cell Biol. 10, 165–177 (2009).

    Article  CAS  PubMed  Google Scholar 

  69. Holloway, E. M. et al. Differentiation of human intestinal organoids with endogenous vascular endothelial cells. Dev. Cell 54, 516–528.e7 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Bar-Ephraim, Y. E., Kretzschmar, K. & Clevers, H. Organoids in immunological research. Nat. Rev. Immunol. 20, 279–293 (2020).

    Article  CAS  PubMed  Google Scholar 

  71. Takahashi, K. & Yamanaka, S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 126, 663–676 (2006).

    Article  CAS  PubMed  Google Scholar 

  72. Tchieu, J. et al. A modular platform for differentiation of human PSCs into all major ectodermal lineages. Cell Stem Cell 21, 399–410.e7 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Volpato, V. & Webber, C. Addressing variability in iPSC-derived models of human disease: guidelines to promote reproducibility. Dis. Model Mech. 13, dmm042317 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Vigilante, A. et al. Identifying extrinsic versus intrinsic drivers of variation in cell behavior in human iPSC lines from healthy donors. Cell Rep. 26, 2078–2087.e3 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Li, W., Germain, R. N. & Gerner, M. Y. High-dimensional cell-level analysis of tissues with Ce3D multiplex volume imaging. Nat. Protoc. 14, 1708–1733 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

This work was supported by the Ralph W. and Grace M. Showalter Trust (K.R.K.), the Indiana CTSI (core pilot grant UL1 TR001108 to K.R.K.), the Indiana Center for Biomedical Innovation (Technology Enhancement Grant to K.R.K.) and the NIH (grants R01AR075018 and R01DC017461 to K.R.K.). Cell lines associated with this study were stored in a facility constructed with support from the NIH (grant C06 RR020128-01). We thank M. Steinhart, C. Nist-Lund, A. Sheets, B. Cooper, S. Heller, B. Woodruff, M. Rendl, P. Rompolas, D. Spandau, J. Foley, R. Rotting, M. Haniffa, M. Boniotto, S. Sahu, S. Sharan, K. Andrykovich, R. Jaenisch, L. Biggs and S. Wickström for constructive feedback and technical assistance during the development of this method.

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Author notes

  1. These authors contributed equally: Wouter H. van der Valk, Sara A. Serdy, CiCi Deakin.

Authors and Affiliations

  1. Department of Otolaryngology, Boston Children’s Hospital, Boston, MA, USA

    Jiyoon Lee, Wouter H. van der Valk, Jin Kim, Anh Phuong Le & Karl R. Koehler

  2. F.M. Kirby Neurobiology Center, Boston Children’s Hospital, Boston, MA, USA

    Jiyoon Lee, Wouter H. van der Valk, Sara A. Serdy, CiCi Deakin, Jin Kim, Anh Phuong Le & Karl R. Koehler

  3. Department of Plastic and Oral Surgery, Boston Children’s Hospital, Boston, MA, USA

    Jiyoon Lee, Jin Kim, Anh Phuong Le & Karl R. Koehler

  4. Department of Surgery, Harvard Medical School, Boston, MA, USA

    Jiyoon Lee

  5. Department of Otolaryngology–Head and Neck Surgery, Harvard Medical School, Boston, MA, USA

    Jiyoon Lee, Wouter H. van der Valk, Jin Kim, Anh Phuong Le & Karl R. Koehler

  6. Department of Otorhinolaryngology and Head & Neck Surgery, Leiden University Medical Center, Leiden, the Netherlands

    Wouter H. van der Valk

  7. Department of Biological Engineering, Wentworth Institute of Technology, Boston, MA, USA

    CiCi Deakin

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Contributions

J.L. and K.R.K. conceived the study and wrote the manuscript. W.H.v.d.V. performed whole-mount immunostaining. W.H.v.d.V., S.A.S. and C.D. performed imaging. J.L., W.H.v.d.V., S.A.S., C.D., J.K., A.P.L. and K.R.K. contributed to figure making, writing and manuscript editing. All authors read and approved the final manuscript.

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Correspondence to Jiyoon Lee or Karl R. Koehler.

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Competing interests

J.L. and K.R.K., with the Indiana University Research and Technology Corporation, have submitted a patent application covering the entire skin organoid induction method (WO2017070506A1). The other authors declare no competing interests.

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Nature Protocols thanks Ming Xing Lei, Yunfang Wang and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Key references used in this protocol

Lee, J. et al. Nature 582, 399–404 (2020): https://doi.org/10.1038/s41586-020-2352-3

Lee, J. et al. Cell Rep. 22, 242–254 (2018): https://doi.org/10.1016/j.celrep.2017.12.007

Koehler, K. R. et al. Nat. Biotechnol. 35, 583–589 (2017): https://doi.org/10.1038/nbt.3840

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Lee, J., van der Valk, W.H., Serdy, S.A. et al. Generation and characterization of hair-bearing skin organoids from human pluripotent stem cells. Nat Protoc 17, 1266–1305 (2022). https://doi.org/10.1038/s41596-022-00681-y

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