오병철 (가천대학교 이길여암당뇨연구원)

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가천대학교 이길여암당뇨연구원

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Adv. Sci., Apr 26 2024, | https://doi.org/10.1002/advs.202307545 Exploring Memory Function Beyond Immune Cells: ANGPTL4-Mediated Memory Functions in Tissue Resident Stem Cells

Se-Ra Park ^1,2, Eun-Kyung Min ^1,2, Soo-Rim Kim ^1,2, Suk-Kyung Kim ^1,2, Kun-Hee Na ^1,3, Chan Hum Park ⁴, YunJae Jung ³, Byung-Chul Oh ⁵, In-Sun Hong ^1,2

¹Department of Health Sciences and Technology, GAIHST, Gachon University, Incheon, 21999, Republic of Korea.

²Department of Molecular Medicine, School of Medicine, Gachon University, Incheon, 406-840, Republic of Korea.

³Department of Microbiology, College of Medicine, Gachon University, Incheon, 21999, Republic of Korea.

⁴Department of Otolaryngology-Head and Neck Surgery, Chuncheon Sacred Heart Hospital, Hallym University College of Medicine, Chuncheon, 24201, Republic of Korea.

⁵Department of Physiology, Lee Gil Ya Cancer and Diabetes Institute, Gachon University College of Medicine, Incheon, 21999, Republic of Korea.

S.R.P., E.K.M., and S.R.K., contributed equally to this work.

CORRESPONDING AUTHORS: Byung-Chul Oh, In-Sun Hong

Abstract

Adapted immune cells are known to develop memory functions that increase resistance to subsequent infections after initial pathogen exposure, however, it is unclear whether non-immune cells, like tissue-resident stem cells, have similar memory functions. Here, it is found that tissue-resident stem cells crucial for tissue regeneration show diminished adverse effects on diverse stem cell functions against successive exposure to foreign antigen (β-glucan) to maintain tissue homeostasis and stability both in vitro and in vivo. These data suggest that endometrial stem cells may possess a robust memory function, in contrast, fully differentiated cells like fibroblasts and vesicular cells do not show these memory mechanisms upon consecutive antigen exposure. Moreover, the pivotal role of Angiopoietin-like 4 (ANGPTL4) in regulating the memory functions of endometrial stem cells is identified through specific shRNA knockdown in vitro and knockout mice in vivo experiments. ANGPTL4 is associated with the alteration of diverse stem cell functions and epigenetic modifications, notably through histone H3 methylation changes and two pathways (i.e., PI3K/Akt and FAK/ERK1/2 signaling) upon consecutive antigen exposure. These findings imply the existence of inherent self-defense mechanisms through which local stem cells can adapt and protect themselves from recurrent antigenic challenges, ultimately mitigating adverse consequences.

논문정보

형식Research article
게재일2024년 04월 (BRIC 등록일 2024-04-29)
연구진국내 연구진
분야 의약학 > 재생의학

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