Lylybell Zhou

Student NameLylybell Zhou
Faculty Mentor NameDaniel Kopinke
CollegeCollege of Medicine
MajorMedical Geography
Research InterestsMuscle regeneration, stem cells
Academic AwardsNational Merit Finalist – 2019
Benacquisto Scholarship – 2019
University Scholars Program – 2020
OrganizationsGator Campus Diplomats, Emergency Medical Response Unit, In Between
Hobbies and Interestspiano, knitting, cross stitch, corgis

Research Project

The Regulatory Role of Desert Hedgehog in Fat Infiltration and Muscle Regeneration

Skeletal muscle has a remarkable ability to regenerate after injury. It is known that a certain population of cells called fibro/adipogenic progenitors (FAPs) are crucial for this process of regeneration by signaling to muscle stem cells to differentiation into myoblasts. FAPs derive their name from their ability to produce extracellular matrix and differentiate into adipocytes. In these cells, the primary cilium is an organelle that has been shown to control stem cell fate and senses cues from the extracellular environment. One signaling pathway that depends on the primary cilium is the Hedgehog (Hh) pathway, which is activated by Sonic (SHH), Desert (DHH), or Indian (IHH) hedgehog ligands. Previous work by the Kopinke lab has shown that FAPs are the main ciliated cell type and activating the Hh pathway within FAPs inhibits their differentiation into fat and improves muscle repair. Furthermore, DHH is the main ligand expressed after acute muscle injury, so it is possible that DHH is the endogenous Hh ligand sensed by FAPs to regulate muscle regeneration and homeostasis.

However, it is unknown how DHH affects regeneration and cellular communication. To evaluate this, we will determine the cellular dynamics of FAPs, satellite, endothelial, immune, and Schwann cells in the absence of DHH (Dhh null mice = Dhh-/-). Since preliminary data from the lab suggest that a lack of DHH results in an increase in fat infiltration and decrease in muscle repair, we expect a disruption in the proliferation and/or differentiation of FAPs and satellite cells.

We will study this by inducing an acute (by cardiotoxin injection) or adipogenic (by glycerol injection) injury in the tibialis anterior (TA) muscle in Dhh-/- and control mice. TAs will be analyzed during the early regenerative phase at 1, 3, 5, and 7 days post injury. My goal is to evaluate how the coordination for muscle regeneration is altered in the absence of DHH. To do this, by immunofluorescence I will analyze proliferation and differentiation of satellite cells (Pax7) and FAPs (Pdgfra, Perilipin) along with the activity of Schwann cells (S100b), endothelial cells (CD31), and immune cells (F4/80). To confirm their proliferation and to further investigate the cellular activity, I will perform RT-qPCR of RNA, isolated from these different time points to assess gene transcription of these cell populations.

This work will further elucidate the process of fat infiltration regulation. Understanding the mechanisms that regulate fat infiltration will allow for the future development of pharmacological targets that would prevent fatty fibrosis in muscular dystrophies and sarcopenia.