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The Role of GATA6 in Embryonic Brown Adipocyte Development Seoyoung Jun
- Format:
- Book
- Thesis/Dissertation
- Author/Creator:
- Jun, Seoyoung, author.
- Language:
- English
- Subjects (All):
- Developmental biology.
- Cellular biology.
- Molecular biology.
- Genetics.
- 0758.
- 0379.
- 0307.
- 0369.
- Local Subjects:
- Developmental biology.
- Cellular biology.
- Molecular biology.
- Genetics.
- 0758.
- 0379.
- 0307.
- 0369.
- Genre:
- Academic theses
- Physical Description:
- 1 electronic resource (103 pages)
- Contained In:
- Dissertations Abstracts International 87-03B
- Place of Publication:
- Ann Arbor : ProQuest Dissertations and Theses, 2025
- Language Note:
- English
- Summary:
- Brown adipose tissue (BAT) is a thermogenic organ that has therapeutic potential to treat metabolic diseases. However, there is a clear lack of knowledge about the brown adipocyte lineage and regulators of adipogenic commitment. To identify mesenchymal cell types along the BAT developmental trajectory, we performed single-cell RNA sequencing (scRNA-seq) of the dorsal-anterior region of mouse embryos. Integrated bioinformatic analyses illustrated a putative lineage hierarchy with early progenitors distinguished by the expression of Cadherin-4 (Cdh4) and late progenitors characterized by Dipeptidyl-peptidase 4 (Dpp4) expression. Using CreER mouse models for lineage tracing, we demonstrated that these late progenitors contribute mostly to the development of the fascia surrounding BAT and minorly to the embryonic brown adipocytes. Further scRNA-seq analyses identified the transcription factor, GATA Binding Protein 6 (Gata6) as a potential regulator of BAT development. Immunostaining analysis showed that GATA6 is strongly and transiently expressed in the developing BAT. To examine the role of GATA6, we selectively deleted Gata6 within the brown adipocyte lineage using a Myf5Cre driver. Interestingly, targeted deletion of Gata6 led to a striking loss of BAT. These results highlight GATA6 as a novel regulator of brown fat progenitor cells. To investigate the mechanism of GATA6, we differentiated human induced pluripotent stem cells (hiPSCs) into brown adipocytes. While adipogenic efficiency requires further optimization, we propose strategies to enhance differentiation in our system. Additionally, we established an ex vivo mouse embryo culture system that demonstrates spontaneous adipogenesis. Our study elucidates the lineage hierarchy of embryonic BAT and establishes GATA6 as a key regulator of its development. Furthermore, we present experimental models that can drive functional studies and expand our understanding of BAT in both mice and humans, paving the way for advanced obesity therapeutics
- Notes:
- Source: Dissertations Abstracts International, Volume: 87-03, Section: B.
- Advisors: Seale, Patrick Committee members: Lampson, Michael; Gallagher, Kimberly; Rea, Philip A.; Zepp, Jarod A.
- Ph.D. University of Pennsylvania 2025
- Local Notes:
- School code: 0175
- ISBN:
- 9798293803095
- Access Restriction:
- Restricted for use by site license
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