Tracing the fate of adipocytes in contracting bone marrow adipose tissue – UROP Spring Symposium 2022

Tracing the fate of adipocytes in contracting bone marrow adipose tissue

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Lily Oles

Pronouns: She/her

Research Mentor(s): Kenneth Lewis
Co-Presenter:
Research Mentor School/College/Department: Molecular & Integrative Physiology / Medicine
Presentation Date: April 20
Presentation Type: Poster
Session: Session 2 – 11am – 11:50am
Room: League Ballroom
Authors: Lily Oles, Kenneth Lewis, Ormond MacDougald
Presenter: 75

Abstract

Bone marrow adipose tissue (BMAT) is highly plastic, as it continues to dramatically expand and contract throughout adulthood through various physiological mechanisms that are still not entirely understood. Adipocytes (including bone marrow adipocytes) were previously thought to be terminally differentiated cells; however, recent studies have shown that rapid adipocyte contraction in mammary and dermal adipose depots depends on dedifferentiation of involved adipocytes. To test whether a similar mechanism is at play in BMAT, we employed a lineage-tracing approach in conditions previously tested to deplete the BMAT. It has been demonstrated that AAV-G-CSF will cause a massive depletion of BMAT through stimulation of hematopoiesis followed by rapid hematopoietic expansion. There are other, more physiological mechanisms that have been shown to also deplete the marrow, including pregnancy and lactation. However, in our attempt to trace adipocytes in pregnant females, tamoxifen injections appeared to induce severe stress on the mice and pregnancies were severely affected. Therefore, we utilized AAV-G-CSF to reliably deplete the BMAT. We aim to understand what becomes of these cells after dedifferentiation and evaluate their potential as a BMSC (bone marrow stromal cell). In our study, mice were IP injected with 75 mg/kg tamoxifen daily for 5 days. AAV was delivered to the mice via IP injection 10 days after completing tamoxifen injections. Confocal microscopy of fresh marrow shows the expected depletion of BMAT, but we failed to observe an increase in stromal reticular cell count. Follow up imaging in immunolabeled cleared marrow plugs will enable quantification of GFP-positive stromal cells within the distal tibia marrow compartment. We are also currently determining expression of genes and proteins involved in adipose function, adipogenesis, and cell death in marrow of the femur, caudal vertebrae, and forelimbs to illuminate the mechanism of BMAT contraction in response to hematopoietic expansion. Moving forward, we plan to dig deeper into this mechanism and then focus our studies on pregnancy to observe if the mechanisms are consistent.

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Biomedical Sciences, Interdisciplinary

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