Shean Jiang
Pronouns: He/Him
Research Mentor(s): Yuji Mishina
Research Mentor School/College/Department: Biological and Material Sciences / Dentistry
Program:
Authors: Shean Jiang, Hiroki Ueharu, Yuji Mishina
Session: Session 5: 2:40 pm – 3:30 pm
Poster: 106
Abstract
Cranial neural crest cells (CNCCs) are multipotent cells that can differentiate into osteoblasts, chondrocytes, myocytes, and adipocytes. CNCCs originate at the neural folds and undergo an epithelial to mesenchymal (EMT) transition and migrate into the pharyngeal arches found on the ventral embryo surface of mice. Mesenchymal cells have the ability to migrate dorsolaterally and differentiate into cartilage, bone, and connective tissues of the face. However, the understanding of how CNCCs determine their differentiation lineage is limited. From previous research, we know that enhanced BMP signaling in NCCs develops ectopic cartilage at embryonic day 14.5 (E14.5) in P0-caACVR1 mutant mouse line. The data suggests that BMP signaling alters CNCCs towards chondrogenesis, instead of prompting chondrogenesis in already committed cells. In this study, we hypothesize that enhanced BMP signaling in CNCCs develops ectopic cartilage through cell fate switching at E10.5, and this study intends to uncover the mechanisms of cell fate specification towards a chondrogenic fate. The mechanism of cell fate determination can be caused by a change in chromatin structure of lineage specific genes. Single-cell ATAC sequencing using CNCCs from the first branchial arch of control and mutant mice at E10.5 revealed that the chromatin region of Sox6 (a gene expressed in chondrocyte) is more accessible in mutants than controls. Other chromatin regions, Sp7 (osteoblasts), Zfp423 (adipocytes), and Pax7 (myocytes) were less accessible in mutants. There was a GATA binding motif frequently found in opened chromatin regions in the genome of mutant mice, including the Sox6 region. The GATA family is known to control cell fate by chromatin modifications. Further gene expression analysis demonstrated that Sox9-positive ectopic chondroprogenitor cells in mutant mice expressed GATA binding protein 6 (GATA 6) and Sox6.
