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.

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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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