Biology subjects

Tylzanowski, P.

Publications and source records attributed to Tylzanowski, P..

2 recordsLinked to original sources

bioRxiv2022

Chromatin architecture and cis-regulatory landscape of the DACT2-SMOC2 locus in the developing synovial joint.

BackgroundSynovial joints form in several steps, starting with the formation of an interzone, a condensation of mesenchymal cells at the sites of prospective joints. Despite the identification of multiple factors essential for formation of interzone, little is known about the regulation of their spatio-temporal gene expression during that process in limb development. Here, we investigated the cis- regulatory landscape of the Wnt-modulator encoding genes DACT2 and SMOC2, both expressed in the forming joint interzone. ResultsMechanically collected interzone and phalange samples, respectively, from chick embryos were found to express acknowledged marker genes (GDF5 and MATN1), as well as DACT2 and SMOC2. Using Targeted Chromatin Capture (T2C) we characterized the 3D chromatin structure of a ~3.45 Mb-long region encompassing DACT2 and SMOC2, which revealed differences at sub-TAD level between interzones and phalange. We identified candidate enhancers (CEs) based on H3-histone marks (H3K427ac and H3K4me1) located in close proximity to the promoters of DACT2 and SMOC2, and further documented these CEs in a zebrafish enhancer assay. ConclusionsOur approach yields new insight into the regulation, in dynamic chromatin context, of two Wnt-signaling modulatory genes during synovial joint induction.

developmental 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↗