Tbx6 Induces Nascent Mesoderm from Pluripotent Stem Cells and Temporally Controls Cardiac versus Somite Lineage Diversification
| Autor: | Sho Haginiwa, Hidenori Kojima, Fumiya Tamura, Yoshifumi Kawamura, Hiroyuki Miyoshi, Kensaku Murano, Shota Kurotsu, Mayumi Oda, Mari Isomi, Masaki Ieda, Peter Andersen, Naoki Goshima, Naoto Muraoka, Taketaro Sadahiro, Hidenori Tani, Hideki Uosaki, Shugo Tohyama, Kuniaki Saito, Hirofumi Nishizono, Keiichi Fukuda, Jun Fujita, Chulan Kwon, Yuka W. Iwasaki |
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| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Male Pluripotent Stem Cells Mesoderm animal structures TBX6 Mice Transgenic Biology Cardiovascular System Article 03 medical and health sciences Mice SOX2 Genetics medicine Paraxial mesoderm Animals Humans Cell Lineage Induced pluripotent stem cell Cells Cultured Mice Inbred ICR Cell Differentiation Cell Biology Cell biology Somite 030104 developmental biology medicine.anatomical_structure Somites embryonic structures Molecular Medicine NODAL T-Box Domain Proteins Reprogramming Transcription Factors |
| Popis: | The mesoderm arises from pluripotent epiblasts and differentiates into multiple lineages; however, the underlying molecular mechanisms are unclear. Tbx6 is enriched in the paraxial mesoderm and is implicated in somite formation, but its function in other mesoderms remains elusive. Here, using direct reprogramming-based screening, single-cell RNA-seq in mouse embryos, and directed cardiac differentiation in pluripotent stem cells (PSCs), we demonstrated that Tbx6 induces nascent mesoderm from PSCs and determines cardiovascular and somite lineage specification via its temporal expression. Tbx6 knockout in mouse PSCs using CRISPR/Cas9 technology inhibited mesoderm and cardiovascular differentiation, whereas transient Tbx6 expression induced mesoderm and cardiovascular specification from mouse and human PSCs via direct upregulation of Mesp1, repression of Sox2, and activation of BMP/Nodal/Wnt signaling. Notably, prolonged Tbx6 expression suppressed cardiac differentiation and induced somite lineages, including skeletal muscle and chondrocytes. Thus, Tbx6 is critical for mesoderm induction and subsequent lineage diversification. |
| Databáze: | OpenAIRE |
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