Differentiation of Keratinocytes in Interfollicular Epidermis in Mammalian Skin

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Homo sapiens
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The interfollicular epidermis is the skin surface layer in between the adnexa (hair follicles, sweat glands, and sebaceous glands). Going from the dermal epidermal junction, the interfollicular epidermis strata include the basal layer (stratum basale), spinous layer (stratum spinosum), granular layer (stratum granulosum), and the cornified layer (stratum corneum). The basal layer consists of keratinocyte stem cells and transit amplifying cells. The spinous, granular, and cornified layers consist of spinous keratinocytes, granular keratinocytes, and corneocytes, respectively. Interfollicular epidermis has a high cell turnover rate. Keratinocyte stem cells self renew throughout adulthood and give rise to transit amplifying cells. Transit amplifying cells undergo several cell cycles before committing to differentiation, first into spinous layer keratinocytes, then into granular layer keratinocytes, and finally into corneocytes. Corneocytes lose their nuclei and cytoplasmic organelles, forming flattened squames that provide a physical barrier against the invasion of pathogens and loss of bodily fluids. For a detailed review, please refer to Zijl et al. 2022, and for the single cell transcriptomic and spatial transcriptomic studies that provide a higher resolution view of human interfollicular epidermis, please refer to Cheng et al. 2018, Wang et al. 2020, Aragona et al. 2020, Haensel et al. 2020, Negri et al. 2023, and Ganier et al. 2024).

The cell lineage path of keratinocytes in interfollicular epidermis is depicted through four cell differentiation steps involving five distinct cellular states: keratinocyte stem cells of epidermal basal layer, transit amplifying cells, spinous keratinocytes, granular keratinocytes, and corneocytes. Each differentiation step is regulated by a distinct combination of regulatory molecules present in the microenvironment of differentiating cells.
Literature References
PubMed ID Title Journal Year
37832539 Single-cell RNA sequencing of human epidermis identifies Lunatic fringe as a novel regulator of the stem cell compartment

Negri, VA, Louis, B, Zijl, S, Ganier, C, Philippeos, C, Ali, S, Reynolds, G, Haniffa, M, Watt, FM

Stem Cell Reports 2023
32187560 Defining Epidermal Basal Cell States during Skin Homeostasis and Wound Healing Using Single-Cell Transcriptomics

Haensel, D, Jin, S, Sun, P, Cinco, R, Dragan, M, Nguyen, Q, Cang, Z, Gong, Y, Vu, R, MacLean, AL, Kessenbrock, K, Gratton, E, Nie, Q, Dai, X

Cell Rep 2020
32843640 Single cell transcriptomics of human epidermis identifies basal stem cell transition states

Wang, S, Drummond, ML, Guerrero-Juarez, CF, Tarapore, E, MacLean, AL, Stabell, AR, Wu, SC, Gutierrez, G, That, BT, Benavente, CA, Nie, Q, Atwood, SX

Nat Commun 2020
35817501 Dynamic regulation of human epidermal differentiation by adhesive and mechanical forces

Zijl, S, Salameti, V, Louis, B, Negri, VA, Watt, FM

Curr Top Dev Biol 2022
30355494 Transcriptional Programming of Normal and Inflamed Human Epidermis at Single-Cell Resolution

Cheng, JB, Sedgewick, AJ, Finnegan, AI, Harirchian, P, Lee, J, Kwon, S, Fassett, MS, Golovato, J, Gray, M, Ghadially, R, Liao, W, Perez White, BE, Mauro, TM, Mully, T, Kim, EA, Sbitany, H, Neuhaus, IM, Grekin, RC, Yu, SS, Gray, JW, Purdom, E, Paus, R, Vaske, CJ, Benz, SC, Song, JS, Cho, RJ

Cell Rep 2018
38165934 Multiscale spatial mapping of cell populations across anatomical sites in healthy human skin and basal cell carcinoma

Ganier, C, Mazin, P, Herrera-Oropeza, G, Du-Harpur, X, Blakeley, M, Gabriel, J, Predeus, AV, Cakir, B, Prete, M, Harun, N, Darrigrand, JF, Haiser, A, Wyles, S, Shaw, T, Teichmann, SA, Haniffa, M, Watt, FM, Lynch, MD

Proc Natl Acad Sci U S A 2024
32728211 Mechanisms of stretch-mediated skin expansion at single-cell resolution

Aragona, M, Sifrim, A, Malfait, M, Song, Y, Van Herck, J, Dekoninck, S, Gargouri, S, Lapouge, G, Swedlund, B, Dubois, C, Baatsen, P, Vints, K, Han, S, Tissir, F, Voet, T, Simons, BD, Blanpain, C

Nature 2020
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