TERT/BMI1-transgenic human dermal papilla cells enhance murine hair follicle formation in vivo
TERT/BMI1-transgenic human dermal papilla cells enhance murine hair follicle formation in vivo
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DOI：
10.1016/j.jdermsci.2022.03.009
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发表时间：
2022-05-01
影响因子：
4.6
通讯作者：
Okochi, Hitoshi
中科院分区：
文献类型：
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作者：
Ikeda, Mayumi;Yabe, Shigeharu;Okochi, Hitoshi
背景：真皮乳头细胞（DPC）是间充质细胞的一种；它们在毛囊诱导中发挥关键作用。在二维培养过程中，它们的毛发诱导性和增殖能力迅速丧失。细胞衰老是由培养条件不足和端粒缩短引起的。我们之前报道过编码端粒酶逆转录酶的TERT和编码人B细胞特异性莫洛尼鼠白血病病毒插入区1（BMI1）的BMI1避免了鼠DPC的衰老并恢复了毛发诱导活性。目的：评估TERT和BMI1在人DPC（hDPC）中的功能。 从人头皮毛发获得的hDPC用单独的TERT (hDP-T)、单独的BMI1 (hDP-B)、TERT和BMI1 (hDP-TB)以及空载体(hDP-E)转导。通过体内室测定评估这些细胞的毛发诱导活性。通过定量PCR（q-PCR）分析基因表达。结果：hDP-TB在体外比hDP-T和hDP-B增殖更多，并且在体内只有hDP-TB表现出毛发诱导性。此外，与hDP-E相比，hDP-TB中VCAN、CTNNB1、LEF1、FGF7和VEGFA的表达升高。结论：TERT和BMI1的过表达延长了培养的hDPC的寿命，并改善了其在小鼠毛囊上的毛发诱导能力。 (C) 2022 作者。由 Elsevier B.V. 代表日本皮肤病研究学会出版。 CC_BY_4.0
Background: Dermal papilla cells (DPCs) are one type of mesenchymal cells; they play a key role on hair follicle induction. Their hair inductivity and proliferation abilities are rapidly lost during the 2-dimensional culture. Cell senescence is induced by inadequate culture conditions and telomere shortening. We previously reported that overexpression of TERT coding telomerase reverse transcriptase and BMI1 coding human B-cell-specific Moloney murine leukemia virus insertion region 1 (BMI1) avoided senescence of murine DPC and restored hair inductive activity.Objective: To evaluate the function of TERT and BMI1 in the human DPCs (hDPCs).Methods: Cultured hDPCs obtained from human scalp hair were transduced with TERT alone (hDP-T), BMI1 alone (hDP-B), both TERT and BMI1 (hDP-TB) and empty vector (hDP-E). The hair inductive activity of those cells was assessed by chamber assay in vivo. Gene expressions were analyzed by quantitative PCR (q-PCR).Results: hDP-TB proliferated more than hDP-T and hDP-B in vitro and only hDP-TB showed hair inductivity in vivo. Moreover, the expressions of VCAN, CTNNB1, LEF1, FGF7 and VEGFA in hDP-TB were elevated compared to those in hDP-E.Conclusion: Overexpression of both TERT and BMI1 extends the life span of cultured hDPCs and ameliorates their hair inducing ability on mouse hair follicles. (C) 2022 The Authors. Published by Elsevier B.V. on behalf of Japanese Society for Investigative Dermatology. CC_BY_4.0