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Status |
Public on Jan 01, 2021 |
Title |
Correlating functional heterogeneity of human dermal fibroblasts with differences in gene expression |
Organism |
Homo sapiens |
Experiment type |
Expression profiling by array
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Summary |
Recent work has identified markers of fibroblast heterogeneity in human dermis. Transforming growth factor-β1 (TGF-β1) promotes fibroblast-to-myofibroblast differentiation, characterised by the expression of α-smooth muscle actin (α-SMA). Human dermal fibroblasts (hDF), treated with TGF-β1, were assayed for differentiation, proliferation and cell shape using the Operetta imaging system. One donor hDF, derived from female 64-year-old breast skin, expressed decreased levels of α-SMA protein. The gene expression profile of this donor hDF was determined using the Agilent microarray system. Four gene candidates (Asporin, ASPN; C-X-C motif chemokine ligand 1, CXCL1; Insulin-like growth factor 1, IGF1; and Wnt family member 4, WNT4) were chosen based on expression values and validated by TaqMan qPCR. Successful knockdown of IGF1 and WNT4 was achieved using MISSION shRNA-based lentiviral treatment. Fibroblast IGF1 knockdown (shIGF1) increased α-SMA mRNA and protein expression; no effect was seen with fibroblast WNT4 knockdown (shWNT4). Here I have characterised hDF phenotype and gene expression with regard to population heterogeneity. This work highlights the role of IGF-1 signalling on α-SMA expression and dermal fibroblast fate. Targeting IGF-1 signalling could provide therapeutic benefit for skin disorders involving aberrant wound healing and excessive fibrosis.
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Overall design |
Enzyme-derived, human dermal fibroblasts from four adult donors. Treated with/without TGF-β1 for 12h/24h and used for Agilent one colour microarray.
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Contributor(s) |
Culley OJ, Watt FM |
Citation(s) |
33889572 |
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Submission date |
Nov 25, 2019 |
Last update date |
Apr 27, 2021 |
Contact name |
Oliver J Culley |
E-mail(s) |
oliver.culley1@gmail.com
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Phone |
+447500 939574
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Organization name |
King’s College London
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Department |
Centre for Stem Cells and Regenerative Medicine
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Lab |
Fiona M Watt
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Street address |
Floor 28, Tower Wing, Guy’s Hospital, Great Maze Pond
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City |
London |
ZIP/Postal code |
SE1 9RT |
Country |
United Kingdom |
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Platforms (1) |
GPL17077 |
Agilent-039494 SurePrint G3 Human GE v2 8x60K Microarray 039381 (Probe Name version) |
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Samples (48)
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Relations |
BioProject |
PRJNA591561 |
Supplementary file |
Size |
Download |
File type/resource |
GSE140962_RAW.tar |
148.9 Mb |
(http)(custom) |
TAR (of TXT) |
Processed data included within Sample table |
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