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Differentiation of Mouse Embryonic Stem Cells into Cortical Interneuron Precursors
Published on: December 3, 2017
Functional evaluation of ES cell-derived endodermal populations reveals differences between Nodal and Activin
Alice E Chen1, Malgorzata Borowiak, Richard I Sherwood
1Department of Stem Cell and Regenerative Biology, Harvard Stem Cell Institute, Harvard University, Cambridge, MA 02138, USA.
Development (Cambridge, England)
|January 8, 2013
Summary
Embryonic stem cells differentiated using Nodal or Activin A show distinct functional differences. This highlights the need for functional evaluation beyond gene expression in stem cell differentiation for pancreas development.
Area of Science:
- Developmental Biology
- Stem Cell Biology
- Endocrinology
Background:
- Embryonic stem (ES) cells offer potential for generating specific cell types, including those from the definitive endoderm like the pancreas and liver.
- Nodal signaling is crucial for definitive endoderm development, and Activin A, a related TGFβ member, is believed to mimic Nodal's activity.
- Understanding the differentiation potential of ES cells is key for regenerative medicine applications.
Purpose of the Study:
- To compare the functional competence of definitive endoderm cells derived from ES cells using Nodal versus Activin A.
- To investigate the in vivo maturation capacity of Pdx1-expressing cells generated from these distinct endodermal populations.
- To emphasize the importance of functional evaluation in stem cell differentiation protocols.
Main Methods:
- In vitro gene expression analysis of ES cell-derived endodermal cell types.
- In vivo functional analysis following transplantation into developing mouse embryos.
- Assessment of Pdx1-expressing cell differentiation into insulin/c-peptide-expressing cells.
Main Results:
- While Nodal and Activin A signaling pathways share downstream effectors, the resulting endodermal cells exhibit distinct functional differences in vivo.
- ES cell-derived endoderm populations show varied competence for pancreatic cell maturation (insulin/c-peptide expression) after transplantation.
- Gene expression profiles alone do not fully predict the functional potential of differentiated stem cells.
Conclusions:
- Functional cell-type evaluation is critical during stepwise stem cell differentiation, complementing gene expression analysis.
- Nodal and Activin A signaling differentially impact the functional maturation of ES cell-derived endoderm.
- These findings have implications for optimizing stem cell differentiation protocols for therapeutic purposes, particularly for pancreatic cell generation.
