ZIC1 transcription factor overexpression in segmental bone defects is associated with brown adipogenic and osteogenic differentiation.

IF 4 2区 医学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY
STEM CELLS Pub Date : 2025-03-27 DOI:10.1093/stmcls/sxaf013
Neelima Thottappillil, Zhao Li, Xin Xing, Shreya Arondekar, Manyu Zhu, Masnsen Cherief, Qizhi Qin, Myles Zhou, Mary Archer, Kristen Broderick, Bruno Pèault, Min Lee, Aaron W James
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引用次数: 0

Abstract

Transcriptional factor regulation is central to the lineage commitment of stem/ progenitor cells. ZIC1 (ZIC family member 1) is a C2H2-type zinc finger transcription factor expressed during development, brown fat, and certain cancers. Previously, we observed that overexpression of ZIC1 induces osteogenic differentiation at the expense of white adipogenic differentiation. In the present study, the feasibility of ZIC1 overexpressed human progenitor cells in critical sized bone defect was studied. To achieve this, human adipose stem/stromal cells with other without lentiviral ZIC1 overexpression were implanted in a femoral segmental defect model in NOD-SCIDγmice. Results showed that ZIC1 overexpressed cells induced osteogenic differentiation by protein markers in a critical sized femoral segment defect compared to empty lentiviral control, although bone union was not observed. Immunohistochemical evaluation showed that implantation of ZIC1 overexpression cells led to an increase in osteoblast antigen expression (RUNX2, OCN), activation of Hedgehog signaling (Patched1) and an increase in brown adipogenesis markers (ZIC1, EBF2). In contrast, no change in bone defect-associated vasculature was observed (CD31, Endomucin). Together, these data suggest that overexpression of the ZIC1 transcription factor in progenitor cells is associated with differentiation towards osteoblastic and brown adipogenic cell fates.

ZIC1转录因子在节段性骨缺损中的过表达与棕色脂肪形成和成骨分化有关。
转录因子调控是干细胞/祖细胞谱系承诺的核心。ZIC1 (ZIC家族成员1)是一种c2h2型锌指转录因子,在发育、棕色脂肪和某些癌症中表达。之前,我们观察到ZIC1的过表达诱导成骨分化,以牺牲白色脂肪分化为代价。在本研究中,我们研究了ZIC1过表达人祖细胞在临界大小骨缺损中的可行性。为了实现这一目标,将其他没有慢病毒ZIC1过表达的人脂肪干细胞/基质细胞植入nod - scid γ小鼠股骨节段缺损模型。结果显示,与空慢病毒对照相比,ZIC1过表达细胞通过蛋白标记诱导了临界大小股骨节段缺损的成骨分化,尽管未观察到骨愈合。免疫组化评价显示,植入ZIC1过表达细胞导致成骨细胞抗原表达(RUNX2, OCN)增加,Hedgehog信号通路(Patched1)激活,棕色脂肪形成标志物(ZIC1, EBF2)增加。相比之下,未观察到骨缺损相关脉管系统的变化(CD31, Endomucin)。综上所述,这些数据表明祖细胞中ZIC1转录因子的过表达与成骨细胞和棕色脂肪细胞的分化有关。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
STEM CELLS
STEM CELLS 医学-生物工程与应用微生物
CiteScore
10.30
自引率
1.90%
发文量
104
审稿时长
3 months
期刊介绍: STEM CELLS, a peer reviewed journal published monthly, provides a forum for prompt publication of original investigative papers and concise reviews. STEM CELLS is read and written by clinical and basic scientists whose expertise encompasses the rapidly expanding fields of stem and progenitor cell biology. STEM CELLS covers: Cancer Stem Cells, Embryonic Stem Cells/Induced Pluripotent Stem (iPS) Cells, Regenerative Medicine, Stem Cell Technology: Epigenetics, Genomics, Proteomics, and Metabonomics, Tissue-Specific Stem Cells, Translational and Clinical Research.
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