Herpelinck, T. | Search bioRxiv

bioRxiv2023

Reorganization of Septin structures regulates early myogenesis

Controlled myogenic differentiation is crucial for developmental formation, homeostatic maintenance and adult repair of skeletal muscle and relies on cell fate determinants in myogenic progenitors or resident stem cells. Proliferating muscle progenitors migrate, adopt spindle shape, align membranes and fuse into multinuclear syncytia. These processes are accompanied by cyto-architectural changes driven by rearranging of cytoskeletal components such as actin and microtubules. Here we highlight septins, the fourth component of the cytoskeleton, to represent an essential structural element of myoblasts. Specifically, Septin9 regulates myoblast differentiation during the early commitment process. Depletion of Septin9 in C2C12 cells and primary myoblasts led to a precocious switch from a proliferative towards a committed progenitor transcriptomic program. Additionally, we report Septin9 undergoing substantial reorganization and downregulation during myogenic differentiation. Together, we propose filamentous septin structures and their controlled reorganization in myoblasts to provide a key temporal regulation mechanism for the differentiation of myogenic progenitors.

cell biology↗

bioRxiv2022

An integrated single-cell atlas of the skeleton from development through adulthood

The recent growth of single-cell transcriptomics has turned single-cell RNA sequencing (scRNA-seq) into a near-routine experiment. Breakthroughs in improving scalability have led to the creation of organism-wide transcriptomic datasets, aiming to comprehensively profile the cell types and states within an organism throughout its lifecycle. To date, however, the skeleton remains a majorly underrepresented organ system in organism-wide atlases. Considering how the skeleton not only serves as the central framework of the vertebrate body but is also the home of the hematopoietic niche and a central player in major metabolic and homeostatic processes, this presents a major deficit in current reference atlas projects. To address this issue, we integrated ten separate scRNA-seq datasets containing limb skeletal cells and their developmental precursors, generating an atlas of 133 332 cells. This limb skeletal cell atlas describes cells across the mesenchymal lineage from the induction of the limb to the adult bone and encompasses 39 different cell states. Furthermore, expanding the repertoire of available time points and cell types within a single dataset allowed for more complete analyses of cell-cell communication or in silico perturbation studies. Taken together, we present a missing piece in the current atlas mapping efforts, which will be of value to researchers in the fields of skeletal biology, hematopoiesis, metabolism and regenerative medicine.

bioinformatics↗