Noncoding dsRNA induces retinoic acid synthesis to stimulate hair follicle regeneration via TLR3

Dongwon Kim; Ruosi Chen; Mary Sheu; Noori Kim; Sooah Kim; Nasif Islam; Eric M. Wier; Gaofeng Wang; Ang Li; Angela Park; Wooyang Son; Benjamin Evans; Victoria Yu; Vicky P. Prizmic; Eugene Oh; Zixiao Wang; Jianshi Yu; Weiliang Huang; Nathan K. Archer; Zhiqi Hu; Nashay Clemetson; Amanda M. Nelson; Anna Chien; Ginette A. Okoye; Lloyd S. Miller; Gabriel Ghiaur; Sewon Kang; Jace W. Jones; Maureen A. Kane; Luis A. Garza

doi:10.1038/s41467-019-10811-y

Noncoding dsRNA induces retinoic acid synthesis to stimulate hair follicle regeneration via TLR3

Dongwon Kim, Ruosi Chen, Mary Sheu, Noori Kim, Sooah Kim, Nasif Islam, Eric M. Wier, Gaofeng Wang, Ang Li, Angela Park, Wooyang Son, Benjamin Evans, Victoria Yu, Vicky P. Prizmic, Eugene Oh, Zixiao Wang, Jianshi Yu, Weiliang Huang, Nathan K. Archer, Zhiqi HuNashay Clemetson, Amanda M. Nelson, Anna Chien, Ginette A. Okoye, Lloyd S. Miller, Gabriel Ghiaur, Sewon Kang, Jace W. Jones, Maureen A. Kane, Luis A. Garza

School of Medicine

Research output: Contribution to journal › Article › peer-review

Abstract

How developmental programs reactivate in regeneration is a fundamental question in biology. We addressed this question through the study of Wound Induced Hair follicle Neogenesis (WIHN), an adult organogenesis model where stem cells regenerate de novo hair follicles following deep wounding. The exact mechanism is uncertain. Here we show that self-noncoding dsRNA activates the anti-viral receptor toll like receptor 3 (TLR3) to induce intrinsic retinoic acid (RA) synthesis in a pattern that predicts new hair follicle formation after wounding in mice. Additionally, in humans, rejuvenation lasers induce gene expression signatures for dsRNA and RA, with measurable increases in intrinsic RA synthesis. These results demonstrate a potent stimulus for RA synthesis by non-coding dsRNA, relevant to their broad functions in development and immunity.

Original language	English (US)
Article number	2811
Journal	Nature communications
Volume	10
Issue number	1
DOIs	https://doi.org/10.1038/s41467-019-10811-y
State	Published - Dec 1 2019

ASJC Scopus subject areas

Chemistry(all)
Biochemistry, Genetics and Molecular Biology(all)
Physics and Astronomy(all)

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Kim, D., Chen, R., Sheu, M., Kim, N., Kim, S., Islam, N., Wier, E. M., Wang, G., Li, A., Park, A., Son, W., Evans, B., Yu, V., Prizmic, V. P., Oh, E., Wang, Z., Yu, J., Huang, W., Archer, N. K., ... Garza, L. A. (2019). Noncoding dsRNA induces retinoic acid synthesis to stimulate hair follicle regeneration via TLR3. Nature communications, 10(1), [2811]. https://doi.org/10.1038/s41467-019-10811-y

Noncoding dsRNA induces retinoic acid synthesis to stimulate hair follicle regeneration via TLR3. / Kim, Dongwon; Chen, Ruosi; Sheu, Mary ; Kim, Noori; Kim, Sooah; Islam, Nasif; Wier, Eric M.; Wang, Gaofeng; Li, Ang; Park, Angela; Son, Wooyang; Evans, Benjamin; Yu, Victoria; Prizmic, Vicky P.; Oh, Eugene; Wang, Zixiao; Yu, Jianshi; Huang, Weiliang; Archer, Nathan K.; Hu, Zhiqi; Clemetson, Nashay; Nelson, Amanda M.; Chien, Anna; Okoye, Ginette A.; Miller, Lloyd S.; Ghiaur, Gabriel ; Kang, Sewon; Jones, Jace W.; Kane, Maureen A.; Garza, Luis A.

In: Nature communications, Vol. 10, No. 1, 2811, 01.12.2019.

Research output: Contribution to journal › Article › peer-review

Kim, D, Chen, R, Sheu, M , Kim, N, Kim, S, Islam, N, Wier, EM, Wang, G, Li, A, Park, A, Son, W, Evans, B, Yu, V, Prizmic, VP, Oh, E, Wang, Z, Yu, J, Huang, W, Archer, NK, Hu, Z, Clemetson, N, Nelson, AM, Chien, A, Okoye, GA, Miller, LS , Ghiaur, G , Kang, S, Jones, JW, Kane, MA & Garza, LA 2019, 'Noncoding dsRNA induces retinoic acid synthesis to stimulate hair follicle regeneration via TLR3', Nature communications, vol. 10, no. 1, 2811. https://doi.org/10.1038/s41467-019-10811-y

Kim, Dongwon ; Chen, Ruosi ; Sheu, Mary ; Kim, Noori ; Kim, Sooah ; Islam, Nasif ; Wier, Eric M. ; Wang, Gaofeng ; Li, Ang ; Park, Angela ; Son, Wooyang ; Evans, Benjamin ; Yu, Victoria ; Prizmic, Vicky P. ; Oh, Eugene ; Wang, Zixiao ; Yu, Jianshi ; Huang, Weiliang ; Archer, Nathan K. ; Hu, Zhiqi ; Clemetson, Nashay ; Nelson, Amanda M. ; Chien, Anna ; Okoye, Ginette A. ; Miller, Lloyd S. ; Ghiaur, Gabriel ; Kang, Sewon ; Jones, Jace W. ; Kane, Maureen A. ; Garza, Luis A. / Noncoding dsRNA induces retinoic acid synthesis to stimulate hair follicle regeneration via TLR3. In: Nature communications. 2019 ; Vol. 10, No. 1.

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abstract = "How developmental programs reactivate in regeneration is a fundamental question in biology. We addressed this question through the study of Wound Induced Hair follicle Neogenesis (WIHN), an adult organogenesis model where stem cells regenerate de novo hair follicles following deep wounding. The exact mechanism is uncertain. Here we show that self-noncoding dsRNA activates the anti-viral receptor toll like receptor 3 (TLR3) to induce intrinsic retinoic acid (RA) synthesis in a pattern that predicts new hair follicle formation after wounding in mice. Additionally, in humans, rejuvenation lasers induce gene expression signatures for dsRNA and RA, with measurable increases in intrinsic RA synthesis. These results demonstrate a potent stimulus for RA synthesis by non-coding dsRNA, relevant to their broad functions in development and immunity.",

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AU - Islam, Nasif

AU - Wier, Eric M.

AU - Wang, Gaofeng

AU - Li, Ang

AU - Park, Angela

AU - Son, Wooyang

AU - Evans, Benjamin

AU - Yu, Victoria

AU - Prizmic, Vicky P.

AU - Oh, Eugene

AU - Wang, Zixiao

AU - Yu, Jianshi

AU - Huang, Weiliang

AU - Archer, Nathan K.

AU - Hu, Zhiqi

AU - Clemetson, Nashay

AU - Nelson, Amanda M.

AU - Chien, Anna

AU - Okoye, Ginette A.

AU - Miller, Lloyd S.

AU - Ghiaur, Gabriel

AU - Kang, Sewon

AU - Jones, Jace W.

AU - Kane, Maureen A.

AU - Garza, Luis A.

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