Identification of distinct non-myogenic skeletal-muscle-resident mesenchymal cell populations.


Mesenchymal progenitors of the lateral plate mesoderm give rise to various cell fates within limbs, including a heterogeneous group of muscle-resident mesenchymal cells. Often described as fibro-adipogenic progenitors, these cells are key players in muscle development, disease, and regeneration. To further define this cell population(s), we perform lineage/reporter analysis, flow cytometry, single-cell RNA sequencing, immunofluorescent staining, and differentiation assays on normal and injured murine muscles. Here we identify six distinct Pdgfra+ non-myogenic muscle-resident mesenchymal cell populations that fit within a bipartite differentiation trajectory from a common progenitor. One branch of the trajectory gives rise to two populations of immune-responsive mesenchymal cells with strong adipogenic potential and the capability to respond to acute and chronic muscle injury, whereas the alternative branch contains two cell populations with limited adipogenic capacity and inherent mineralizing capabilities; one of the populations displays a unique neuromuscular junction association and an ability to respond to nerve injury.





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Publication Info

Leinroth, Abigail P, Anthony J Mirando, Douglas Rouse, Yoshihiko Kobayahsi, Purushothama Rao Tata, Helen E Rueckert, Yihan Liao, Jason T Long, et al. (2022). Identification of distinct non-myogenic skeletal-muscle-resident mesenchymal cell populations. Cell reports, 39(6). p. 110785. 10.1016/j.celrep.2022.110785 Retrieved from

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Purushothama Rao Tata

Associate Professor of Cell Biology

Lung regeneration
Lung stem cells
Cell plasticity
Organoid models
Lung Fibrosis
Single Cell Biology


Joe Chakkalakal

Associate Professor in Orthopaedic Surgery

Laboratory of Neuromuscular Development, Regeneration, and Aging

We study the cellular and molecular mechanisms underlying neuromuscular development, regeneration, and aging with an emphasis on understanding stem and progenitor cell fate and function, and stem cell niche biology. We are affiliated with the Departments of Orthopaedic Surgery and Cell Biology as part of the Duke Orthopaedic Cellular, Developmental, and Genome Laboratories within the Duke University School of Medicine.

Aging-related declines in neuromuscular regeneration:

Aging is associated with significant deficiencies in skeletal muscle regeneration. We believe the inhibition of regenerated aged myofiber recovery coupled with interstitial pathological infiltrate and fibrosis are due to impairments in the reconstitution of the neuromuscular junction (NMJ), a specialized site where the synapse between a motor axon terminal and myofiber is located. Current studies include examining the cellular basis for the restoration of NMJs after injury. We are also pursuing mechanisms such as the manipulation of relevant stem and progenitor cell populations that may alter NMJ reconstitution after injury and how they impact myofiber recovery, interstitial pathological infiltrate, and fibrosis.

Postnatal neuromuscular growth and the consequences of pediatric cancer therapies:

Neuromuscular impairments are among the aging-related phenotypes observed earlier in pediatric cancer survivors. Early adolescence to adulthood is a period of significant skeletal muscle growth with active stem and progenitor cell activity that is sensitive to pediatric cancer therapies such as radiation and chemotherapy. Current studies involve examining how modulations in the cellular composition of skeletal muscle, the fate of stem and progenitor cell populations, and alterations of the muscle stem cell niche from early adolescence to adulthood impact healthy aging. We are also pursuing strategies to alleviate the near and long term impact of pediatric cancer therapies during this dynamic stage of neuromuscular growth.


Matthew James Hilton

Professor in Orthopaedic Surgery

A long-term interest of the Hilton lab is to uncover the molecular circuitry regulating lineage commitment, proliferation, and differentiation of skeletal stem cells, chondrocytes, and osteoblasts. My laboratory uses genetic mouse models and primary cell culture techniques coupled with biochemistry to answer questions regarding skeletal stem cell self-renewal/differentiation, chondrogenesis, and osteoblastogenesis. Recently my lab has generated novel data from a variety of Notch gain and loss-of-function mutant mice demonstrating the importance of Notch signaling in each of these processes. We are currently investigating the exact Notch signaling mechanisms at play during skeletal development, disease, and repair. Additional studies are also focused on identifying and understanding the molecular mechanisms underlying various congenital skeletal pathologies, including Multiple Herediatry Exostoses (MHE) and Preaxial Polydactyly (PPD).

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