Keratinocytes
The sentinels of our skin
Credit: Art by Nelli Aghekyan. Set in motion by Dr. Emanuele Petretto. Words by Dr. Suruchi Poddar. Project Coordinator: Dr. Masia Maksymowicz. Series Director: Dr. Radhika Patnala
#Extraordinarycelltypes #sciart #lifescience
Let’s meet the keratinocytes
Ever wondered why the thickness of the skin on different parts of the body differs, such as the skin on the neck is much thinner than on the soles of the feet? The difference in the type and amount of keratin, a protein produced by different tissues, impart distinct resilience characteristics to them (1). Keratin is the intermediate filament (IF) protein produced by keratinocytes (2). The skin on our hands, feet, face, etc. is nothing but a sheet of keratinocytes. The outermost layer of the skin is called the epidermis, which is made up of 90% of keratinocytes (3). Being a dominant cell type of the epidermis, keratinocytes act as the first line of defense to save an organism from the assaults of the external environment. Designed to perform important immune and protective functions, keratinocytes protect us from UV exposure and microbial invasion (4). They are also involved in wound repair and maintaining skin hydration (2).
The layers of beauty and the layer-travelers
Skin is the largest organ of the human body. Human skin, particularly the epidermis, is one of the major indicators of an individual’s health and plays a significant role in a person’s appearance (1). The Epidermis is divided into four layers namely stratum basale (basal layer), stratum spinosum (spinous layer), stratum granulosum (granular layer), and stratum corneum (cornified layer) (5). Maintenance of structural architecture and adequate barrier protection depends on a balanced process of keratinocyte replenishment.
On average, a keratinocyte flakes off from the cornified layer in approximately 30–40 days (6). Therefore, as the cells from the upper layers slough off, more keratinocytes proliferate in the basal layer of the skin. They are then pushed through the epidermis to reach the granular layer (7). During the progression towards the epidermal surface (cornified layer) keratinocytes undergo vast changes in their shape from cuboidal to columnar to flattened cells of the cornified layer (5). They also become granulated, with granular keratinocytes containing keratohyalin granules that are responsible for binding intermediate keratin filaments, keeping them together (6).
Holding it tight during wound healing
Keratinocytes not only act as an outer barrier against the environment but also help in healing and restoring skin after an injury. They play a meaningful role in the proliferative phase of wound healing which is characterized by the migration and proliferation of keratinocytes to the site of injury thus forming a new epidermal layer (8,9) This reparative process of recreation of the lost or damaged tissue with new epithelium is called re-epithelialization.
The cells in the new epidermal barrier are held together in a zipper-like fashion by structures known as tight junctions. They provide the ‘tightness’ to the cells required to seal the intercellular spaces in a newly formed epidermal structure (10). The shape taken up by the cells during this process is called Kelvin’s tetrakaidecahedron: a 14-sided solid with six rectangular and eight hexagonal sides. This shape is known as the best shape for filling up spaces along with the formation of tight junctions with the neighboring cells (11). Alterations in tight junctions in the skin can sometimes lead to a chronic disease condition called atopic dermatitis, commonly known as eczema (12).
Keratinocytes so far and their future
Since Rheinwald and Green’s pioneering work was published in 1975, the year 2025 will celebrate the 50th year of a successful cell culture of human keratinocytes (13). It all started when James Rheinwald who was a postdoc in Prof. Howard Green’s laboratory at MIT successfully identified the optimum culture conditions to grow primary epidermal keratinocytes while studying a teratoma cell line (14). Since then keratinocyte cultures have been used in many translational and dermatological studies focusing on cosmetics development, toxicology, cancer, wound healing, aging, etc. Normal human epidermal keratinocytes can be obtained from juvenile foreskin and various other adult body tissues such as the face, breast, abdomen, and thighs (15).
The half-century of tissue culture of keratinocytes has enabled incredible innovation and advancements in the field of epidermal biology and pathology. The field of keratinocyte research continues to grow and evolve in terms of its interaction with other cell types, cell culture platforms, immunomodulation, and many more.
Recognizing and appreciating the labs working in this space
- Ramsey Laboratory, Brigham and Women’s Hospital, Massachusetts, USA. https://ramseylab.bwh.harvard.edu/
- Rieger Research Lab, University of Miami, Florida, USA. https://biology.as.miami.edu/research-labs/rieger-research-lab/sandra-rieger/index.html
- Skin Bioengineering Laboratory, Monash University, Melbourne, Australia. https://www.monash.edu/medicine/ccs/surgery-alfred/research/skin-tissue-lab
- Instituto de Tecnologia Química e Biológica, Oeiras, Portugal. https://www.itqb.unl.pt/labs/biomolecular-diagnostic/research , Twitter: @itqbunl
- The Gautrot Lab, Queen Mary University of London, London. http://biointerfaces.qmul.ac.uk/research-themes/
- Laboratory of Skin Biology, National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS). Maryland, USA. https://www.niams.nih.gov/labs/morasso-lab
- Revivo Biosystems, Singapore. https://www.revivobio.com/expertise
- Fibroheal Woundcare Pvt. Ltd., Bangalore, Karnataka, India. https://fibroheal.com/ , Twitter: @Fibroheal1
- Biomaterial and Tissue Engineering Laboratory, Indian Institute of Technology (Guwahati), India. https://www.iitg.ac.in/biman.mandal/index.html
- Tissue Engineering and Biomicrofluidics Laboratory, Indian Institute of Technology (BHU), Varanasi, India. https://iitbhu.ac.in/dept/bme/people/skmahtobme
References
- Bragulla, Hermann H, and Dominique G Homberger. “Structure and functions of keratin proteins in simple, stratified, keratinized and cornified epithelia.” Journal of anatomy vol. 214,4 (2009): 516–59. doi:10.1111/j.1469–7580.2009.01066.x
- Wang, Fengrong et al. “Skin Keratins.” Methods in enzymology vol. 568 (2016): 303–50. doi:10.1016/bs.mie.2015.09.032
- Mestrallet, Guillaume et al. “Skin Immunity and Tolerance: Focus on Epidermal Keratinocytes Expressing HLA-G.” Frontiers in immunology vol. 12 772516. 6 Dec. 2021, doi:10.3389/fimmu.2021.772516
- Blum, Franklin R. et al. “Pediatric Dermatology and Common Skin Conditions.” Encyclopedia of Child and Adolescent Health (First Edition), edited by Bonnie Halpern-Felsher, Academic Press, 2023, pp. 699–732. ScienceDirect, https://doi.org/10.1016/B978-0-12-818872-9.00093-5
- Hegde, A., Ananthan, A.S., Kashyap, C. et al. “Wound Healing by Keratinocytes: A Cytoskeletal Perspective.” Journal of Indian Institute of Science vol. 101 (2021): 73–80. https://doi.org/10.1007/s41745-020-00219-9
- Houben, E et al. “A keratinocyte’s course of life.” Skin pharmacology and physiology vol. 20,3 (2007): 122–32. doi:10.1159/000098163
- Anderton, Holly, and Suhaib Alqudah. “Cell death in skin function, inflammation, and disease.” The Biochemical journal vol. 479,15 (2022): 1621–1651. doi:10.1042/BCJ20210606
- Guo, S, and L A Dipietro. “Factors affecting wound healing.” Journal of dental research vol. 89,3 (2010): 219–29. doi:10.1177/0022034509359125
- Piipponen, Minna et al. “The Immune Functions of Keratinocytes in Skin Wound Healing.” International journal of molecular sciences vol. 21,22 8790. 20 Nov. 2020, doi:10.3390/ijms21228790
- Brandner, J M et al. “Epidermal tight junctions in health and disease.” Tissue barriers vol. 3,1–2 e974451. 3 Apr. 2015, doi:10.4161/21688370.2014.974451
- Yokouchi, Mariko et al. “Epidermal cell turnover across tight junctions based on Kelvin’s tetrakaidecahedron cell shape.” eLife vol. 5 e19593. 29 Nov. 2016, doi:10.7554/eLife.19593
- Katsarou, Spyridoula et al. “The Role of Tight Junctions in Atopic Dermatitis: A Systematic Review.” Journal of clinical medicine vol. 12,4 1538. 15 Feb. 2023, doi:10.3390/jcm12041538
- Poumay, Yves, and Emilie Faway. “Human epidermal keratinocytes in culture: a story of multiple recipes for a single cell type.” Skin pharmacology and physiology, 10.1159/000534137. 16 Sep. 2023, doi:10.1159/000534137
- Rheinwald, J G, and H Green. “Serial cultivation of strains of human epidermal keratinocytes: the formation of keratinizing colonies from single cells.” Cell vol. 6,3 (1975): 331–43. doi:10.1016/s0092–8674(75)80001–8
- Jahn, Magdalena et al. “Different immortalized keratinocyte cell lines display distinct capabilities to differentiate and reconstitute an epidermis in vitro.” Experimental dermatology vol. 33,1 (2024): e14985. doi:10.1111/exd.14985
About the author:
DR. SURUCHI PODDAR
Content Editor The League of Extraordinary Cell Types, Sci-Illustrate Stories
Dr. Poddar received a PhD in Biomedical Engineering from the Indian Institute of Technology-Banaras Hindu University (IIT-BHU), Varanasi, India. She started her career as a postdoctoral researcher in 2020 with the Nanoscience Technology Center at the University of Central Florida, Orlando where she worked on a multi-organ human-on-a-chip system. Currently, she is working on solid-state nanopore technology at Wake Forest University, North Carolina. When not working, she enjoys watching movies, cooking food, and exploring new places, restaurants, and attractions.
About the artist:
NELLY AGHEKYAN
Contributing Artist The League of Extraordinary Cell Types, Sci-Illustrate Stories
Nelli Aghekyan did a bachelor’s and master’s in Architecture in Armenia, after studying architecture and interior design for 6 years, she concentrated on her drawing skills and continued her path in the illustration world. She works mainly on children’s book illustrations, some of her books are now being published. Currently living in Italy, she works as a full-time freelance artist, collaborating with different companies and clients.
About the animator:
DR. EMANUELE PETRETTO
Animator The League of Extraordinary Cell Types, Sci-Illustrate Stories
Dr. Petretto received his Ph.D. in Biochemistry at the University of Fribourg, Switzerland, focusing on the behavior of matter at nanoscopic scales and the stability of colloidal systems. Using molecular dynamics simulations, he explored the delicate interaction among particles, interfaces, and solvents.
Currently, he is fully pursuing another delicate interaction: the intricate interplay between art and science. Through data visualization, motion design, and games, he wants to show the wonders of the complexity surrounding us.
About the series:
The League of Extraordinary Cell types
The team at Sci-Illustrate and Endosymbiont bring to you an exciting series where we dive deep into the wondrous cell types in our body, that make our hearts tick ❤.
