Tbx6 revealed as crucial to heart and skeleton formation from stem cells

August 10, 2018, University of Tsukuba
Tbx6 revealed as crucial to heart and skeleton formation from stem cells
The mesoderm induced by Tbx6 from fibroblasts of mouse. The scale bar represents 100μm. Credit: University of Tsukuba

Many studies have attempted to identify a single transcription factor that can induce formation of the mesoderm, an early layer in embryonic development, without help from other cellular proteins. None have been successful, until now.

In a new study published in Cell Stem Cell, titled "Tbx6 Induces Nascent Mesoderm from Pluripotent Stem Cells and Temporally Controls Cardiac versus Somite Lineage Diversification," a research team, including experts from the University of Tsukuba, screened over 50 transcription factors and found that Tbx6 alone was able to stimulate formation in laboratory-grown stem cells, and could cause those stem cells to become cardiovascular or musculoskeletal cells.

Pluripotent stem cells provide an important window into the mechanisms of cell differentiation, a critical process during development and maintenance of tissues in humans and other animals, and are vital to the framework of . Despite recent successes in understanding and guiding , the overall molecular system required for the induction of the mesoderm and its subsequent specialization into tissue-specific cell types has remained elusive because its processes are dynamic, and previous studies have been too small to provide conclusive data.

"Tbx6 was already known to be active in formation of musculoskeletal tissue—Tbx6 mutant mice produce ectopic neural tubes at the expense of musculoskeletal tissue—but its expression and function in early/nascent mesoderm and mesodermal derivatives, including cardiovascular lineages, have been largely unknown," says Masaki Ieda, corresponding author on the study. "We were surprised to learn that Tbx6 has a broader role in the formation of mesoderm from ."

In the study, temporary production of Tbx6 caused the formation of mesoderm that later produced cardiovascular cells, while continuous Tbx6 expression suppressed this cardiovascular-forming mesoderm and caused formation of mesoderm that later produced musculoskeletal .

"Our analyses revealed a connection between early Tbx6 expression and cardiovascular lineage differentiation, and we believe that our study and similar studies may change the current view of lineage specification during development," Dr. Ieda explains. "Importantly, this essential and unappreciated function of Tbx6 in mesoderm and cardiovascular specification is conserved from lower organisms to mammals, so this discovery may have wide-ranging applicability in regenerative medicine."

In addition to the broader role of Tbx6, the researchers have shown the usefulness of a new direct reprogramming-based approach to screen for important transcription factors that may regulate cell differentiation.

Tbx6 has dramatic effects on mesoderm formation and subsequent stem cell differentiation. This study has enhanced the understanding of mesoderm development and has provided new methods that may enhance future regenerative medicine research.

Explore further: Cell contacts in embryonic development determine cellular fate

More information: Taketaro Sadahiro et al, Tbx6 Induces Nascent Mesoderm from Pluripotent Stem Cells and Temporally Controls Cardiac versus Somite Lineage Diversification, Cell Stem Cell (2018). DOI: 10.1016/j.stem.2018.07.001

Related Stories

Recommended for you

EPA adviser is promoting harmful ideas, scientists say

March 22, 2019

The Trump administration's reliance on industry-funded environmental specialists is again coming under fire, this time by researchers who say that Louis Anthony "Tony" Cox Jr., who leads a key Environmental Protection Agency ...

The taming of the light screw

March 22, 2019

DESY and MPSD scientists have created high-order harmonics from solids with controlled polarization states, taking advantage of both crystal symmetry and attosecond electronic dynamics. The newly demonstrated technique might ...

Male fish can thank genes for colourful looks

March 22, 2019

Striking traits seen only in males of some species – such as colourful peacock feathers or butterfly wings – are partly explained by gene behaviour, research suggests.

Coffee-based colloids for direct solar absorption

March 22, 2019

Solar energy is one of the most promising resources to help reduce fossil fuel consumption and mitigate greenhouse gas emissions to power a sustainable future. Devices presently in use to convert solar energy into thermal ...


Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.