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Cited by 53Dermatological and COVID-19 studiesHair Growth and DisordersSARS-CoV-2 and COVID-19 Research

Establishment of Human Pluripotent Stem Cell‐Derived Skin Organoids Enabled Pathophysiological Model of SARS‐CoV‐2 Infection

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Ma, Jie, liu, Jia, Gao, Dunqin, Li, Xiao, Zhang, Qiyu, Lv, Luye, Wang, Yujie, Li, Jun +11 more·2022·Advanced Science
DOI 10.1002/advs.202104192PMC PMC8895131
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Abstract

Coronavirus disease 2019 (COVID-19) patients with impact on skin and hair loss are reported. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is detected in the skin of some patients; however, the detailed pathological features of skin tissues from patients infected with SARS-CoV-2 at a molecular level are limited. Especially, the ability of SARS-CoV-2 to infect skin cells and impact their function is not well understood. A proteome map of COVID-19 skin is established here and the susceptibility of human-induced pluripotent stem cell (hiPSC)-derived skin organoids with hair follicles and nervous system is investigated, to SARS-CoV-2 infection. It is shown that KRT17+ hair follicles can be infected by SARS-CoV-2 and are associated with the impaired development of hair follicles and epidermis. Different types of nervous system cells are also found to be infected, which can lead to neuron death. Findings from the present work provide evidence for the association between COVID-19 and hair loss. hiPSC-derived skin organoids are also presented as an experimental model which can be used to investigate the susceptibility of skin cells to SARS-CoV-2 infection and can help identify various pathological mechanisms and drug screening strategies.

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  • PSOs are already being adopted for various applications including disease modeling and regenerative therapy.

    “Despite their recent discovery, PSOs are already being adopted for various applications including disease modeling and regenerative therapy [5,7–9], yet several considerations remain, such as their limited maturation and efficiency, and non-anatomical organization of dermal and epidermal compartments.”

    From Efficient Generation of Skin Organoids from Pluripotent Cells via Defined Extracellular Matrix Cues and Morphogen Gradients in a Spindle‐Shaped Microfluidic Device (2024) · cites this paper as [9]

    The Introduction (page not provided) says the authors used a skin organoid to model SARS-CoV-2 infection, supporting disease modeling. The Discussion (page not provided) proposes treating complex skin disease with organoids as a possible future application; it does not show that PSOs are already being adopted for regenerative therapy. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

  • hiPSC-derived skin organoids have hair follicles, pigmentation, dermal stratification, appendage patterning, and innervation.

    “Recent advances in human induced pluripotent stem cell (hiPSC) technology have enabled the generation of skin organoids (SKO) with hair follicles, pigmentation, dermal stratification, appendage patterning, and innervation.[ 25 , 26 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 ]”

    From Coordinated Development of Immune Cell Populations in Vascularized Skin Organoids from Human Induced Pluripotent Stem Cells (2025) · cites this paper as [30]

    The Results (‘Formation of Skin Organoids with Various hiPSC-Derived Skin Cells’; page unavailable) report mature hair follicles and a stratified epithelium. The Results (‘SARS-CoV-2 Can Infect the Nervous System of Skin’; page unavailable) also show a neuronal network around the follicles. But the paper identifies melanosome-related proteins rather than demonstrating visible pigmentation, and it does not establish dermal stratification or appendage patterning; epithelial stratification is not dermal stratification. (LLM, conf=0.87)

    Experimental — accuracy not yet measured

  • Previous human SKO models were devoid of vascularization and immune cells.

    “Previous human SKO models were devoid of vascularization and immune cells.[ 25 , 26 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 59 ]”

    From Coordinated Development of Immune Cell Populations in Vascularized Skin Organoids from Human Induced Pluripotent Stem Cells (2025) · cites this paper as [30]

    The Results section describes this skin organoid’s cell types and reports proteins associated with vascular-related cells, but does not establish whether it has vascularization. Neither the supplied passages nor searches for vascularization and immune cells establish that this model—or previous human skin organoid models—lacked both features. Page numbers were not available in our copy. (LLM, conf=0.72)

    Experimental — accuracy not yet measured

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Cited by

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Authors
Ma, J., liu, J., Gao, D., Li, X., Zhang, Q., Lv, L., Wang, Y., Li, J., Zhu, Y., Wu, Z., Hu, H., Li, Y., Ma, L., Liu, Q., Hu, Z., Zhang, S., Zhou, Y., Wang, M., & Leng, L.
Affiliations
  • Beijing Proteome Research Center (CN)
  • Chinese Academy of Sciences (CN)
  • Chinese Academy of Medical Sciences & Peking Union Medical College (CN)
  • State Key Laboratory of Proteomics Beijing Proteome Research Center National Center for Protein Sciences (Beijing) Beijing Institute of Lifeomics Beijing 102206 China
  • Institute of NBC Defense Beijing 102205 China
  • Anhui Medical University (CN)
  • Huazhong University of Science and Technology (CN)
  • State Key Laboratory of Virology Wuhan Institute of Virology Center for Biosafety Mega‐Science Chinese Academy of Sciences Wuhan 430071 China
Corresponding author
  • Zhang, Shuyang
  • Zhou, Yiwu
  • Wang, Manli
  • Leng, Ling
ORCID
Venue
Advanced Science
Publisher
Wiley
Published
2021-12-31
Volume
9
Issue
7
Pages
e2104192-e2104192
ISSN
2198-3844 (ISSN-L)
DOI
10.1002/advs.202104192
PMC
PMC8895131
OpenAlex
W4205146747
Cited by
53
References
10
Citations by year
2026: 4 · 2025: 14 · 2024: 17 · 2023: 12 · 2022: 5 · 2021: 1
FWCI
7.78
Type
journal article
Language
en
Open access
Licence
Locations
  • Advanced Science (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
National Key Research and Development Program of China (2020YFE0202200)
Topics
  • Health Sciences › Medicine › Dermatology › Dermatological and COVID-19 studies
  • Health Sciences › Medicine › Urology › Hair Growth and Disorders
  • Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
Keywords
SARS-CoV-2, COVID-19 pandemic, skin organoids, human induced pluripotent stem cells, hair follicle, hair loss, skin proteome, neuronal cell death, epidermal development, pathophysiological model, drug screening
MeSH terms
COVID-19, SARS-CoV-2, Humans, Models, Biological, Nervous System, Organoids, Skin, Hair Follicle, Proteomics, Induced Pluripotent Stem Cells

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