in the regulation of key transcription factors that drive both developmental and cancer EMT [2, 15, 18–22]. Furthermore, posttranscriptional regulation is often coordinated for functionally
related targets; for example, multiple miRNAs recently have been
shown to cooperate to combinatorially regulate epithelial and mesenchymal markers to facilitate EMT [23]. With these many modes
of EMT regulation beyond transcription, it will become increasingly important, as we continue to define contexts of partial EMT,
to fully understand how regulation beyond transcriptional control
participates in the dynamics of partial EMT.
As the impact of partial EMT in the context of both development and disease becomes clearer, new questions begin to emerge:
Are these partial EMT states controlled cell autonomously? Is
partial EMT a “halted” program or an alternative program? What
molecular signatures underlie distinct states within the spectrum of
partial EMT? Mathematical modeling approaches are providing
insight into the factors likely to be involved in partial EMT
[24, 25]. However, these approaches are limited by the knowledge
of which combination of factors, most of which are currently
unknown, define the spectrum of partial EMTs. Single-cell
RNA-sequencing (scRNA-seq) is currently the best technology to
resolve the heterogeneity of states in between an epithelial and a
mesenchymal cell state [26]. The use of scRNA-seq in both developmental and cancer EMT contexts, in combination with multiplex
fluorescent in situ hybridization for spatial information, will
provide new molecular markers for the various partial EMTs.
Understanding the molecular mechanisms underpinning the transitional states across partial EMT will begin to illuminate how these
states are intrinsically controlled. Furthermore, understanding the
molecular signatures defining intermediate states across partial
EMT will enhance modeling approaches to better predict the
dynamics of transition states [27], which will better define the
partial EMT programs.
The importance of partial EMT in both development and
cancer is becoming increasingly well established. As technologies
and methods emerge to characterize and define the heterogeneity
of states comprising the spectrum of partial EMT states, this information will provide new insights into important and complex
developmental processes, as well as provide novel targets for cancer
therapies.
Acknowledgments
We thank members of the Bronner lab for helpful discussions. The
authors are supported by the National Institutes of Health K99
DE028592 (E.J. Hutchins), R01DE027538 and P01 HD037105
(M.E. Bronner).
A Spectrum of Cell States During EMT
5
related targets; for example, multiple miRNAs recently have been
shown to cooperate to combinatorially regulate epithelial and mesenchymal markers to facilitate EMT [23]. With these many modes
of EMT regulation beyond transcription, it will become increasingly important, as we continue to define contexts of partial EMT,
to fully understand how regulation beyond transcriptional control
participates in the dynamics of partial EMT.
As the impact of partial EMT in the context of both development and disease becomes clearer, new questions begin to emerge:
Are these partial EMT states controlled cell autonomously? Is
partial EMT a “halted” program or an alternative program? What
molecular signatures underlie distinct states within the spectrum of
partial EMT? Mathematical modeling approaches are providing
insight into the factors likely to be involved in partial EMT
[24, 25]. However, these approaches are limited by the knowledge
of which combination of factors, most of which are currently
unknown, define the spectrum of partial EMTs. Single-cell
RNA-sequencing (scRNA-seq) is currently the best technology to
resolve the heterogeneity of states in between an epithelial and a
mesenchymal cell state [26]. The use of scRNA-seq in both developmental and cancer EMT contexts, in combination with multiplex
fluorescent in situ hybridization for spatial information, will
provide new molecular markers for the various partial EMTs.
Understanding the molecular mechanisms underpinning the transitional states across partial EMT will begin to illuminate how these
states are intrinsically controlled. Furthermore, understanding the
molecular signatures defining intermediate states across partial
EMT will enhance modeling approaches to better predict the
dynamics of transition states [27], which will better define the
partial EMT programs.
The importance of partial EMT in both development and
cancer is becoming increasingly well established. As technologies
and methods emerge to characterize and define the heterogeneity
of states comprising the spectrum of partial EMT states, this information will provide new insights into important and complex
developmental processes, as well as provide novel targets for cancer
therapies.
Acknowledgments
We thank members of the Bronner lab for helpful discussions. The
authors are supported by the National Institutes of Health K99
DE028592 (E.J. Hutchins), R01DE027538 and P01 HD037105
(M.E. Bronner).
A Spectrum of Cell States During EMT
5