TERT/BMI1 转基因人真皮乳头细胞增强体内小鼠毛囊的形成。
TERT/BMI1-transgenic human dermal papilla cells enhance murine hair follicle formation in vivo.
机构信息
Department of Dermatology, Saitama Medical University, Saitama, Japan; Department of Regenerative Medicine, Research Institute, National Center for Global Health and Medicine, Tokyo, Japan.
Department of Regenerative Medicine, Research Institute, National Center for Global Health and Medicine, Tokyo, Japan.
出版信息
J Dermatol Sci. 2022 May;106(2):78-85. doi: 10.1016/j.jdermsci.2022.03.009. Epub 2022 Mar 30.
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.
背景
真皮乳头细胞（DPCs）是一种间质细胞，在毛囊诱导中起着关键作用。它们的毛发生诱导能力和增殖能力在二维培养中迅速丧失。细胞衰老由培养条件不足和端粒缩短引起。我们之前报道过，端粒酶逆转录酶编码 TERT 和人 B 细胞特异性 Moloney 鼠白血病病毒插入区 1（BMI1）编码 BMI1 的过表达可避免小鼠 DPC 的衰老并恢复毛发生诱导活性。
目的
评估 TERT 和 BMI1 在人真皮乳头细胞（hDPCs）中的功能。
方法
用 TERT 单独（hDP-T）、BMI1 单独（hDP-B）、TERT 和 BMI1 两者（hDP-TB）和空载体（hDP-E）转导培养的来自人头皮毛发的 hDPCs。通过体内腔室测定评估这些细胞的毛发生诱导活性。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，只有 hDP-TB 在体内具有毛发生诱导活性。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 的过表达可延长培养的 hDPCs 的寿命，并改善它们对小鼠毛囊的毛发生诱导能力。
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