Generation of glucose-sensitive insulin-secreting beta-like cells from human embryonic stem cells by incorporating a synthetic lineage-control network.
J Biotechnol
; 259: 39-45, 2017 Oct 10.
Article
in En
| MEDLINE
| ID: mdl-28739109
ABSTRACT
We previously reported novel technology to differentiate induced pluripotent stem cells (IPSCs) into glucose-sensitive insulin-secreting beta-like cells by engineering a synthetic lineage-control network regulated by the licensed food additive vanillic acid. This genetic network was able to program intricate expression dynamics of the key transcription factors Ngn3 (neurogenin 3, OFF-ON-OFF), Pdx1 (pancreatic and duodenal homeobox 1, ON-OFF-ON) and MafA (V-maf musculoaponeurotic fibrosarcoma oncogene homologue A, OFF-ON) to guide the differentiation of IPSC-derived pancreatic progenitor cells to beta-like cells. In the present study, we show for the first time that this network can also program the expression dynamics of Ngn3, Pdx1 and MafA in human embryonic stem cell (hESC)-derived pancreatic progenitor cells and drive differentiation of these cells into glucose-sensitive insulin-secreting beta-like cells. Therefore, synthetic lineage-control networks appear to be a robust methodology for differentiating pluripotent stem cells into somatic cell types for basic research and regenerative medicine.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Insulin-Secreting Cells
/
Gene Regulatory Networks
/
Synthetic Biology
/
Human Embryonic Stem Cells
Type of study:
Diagnostic_studies
Limits:
Humans
Language:
En
Journal:
J Biotechnol
Journal subject:
BIOTECNOLOGIA
Year:
2017
Document type:
Article
Affiliation country: