Top-down inhibition (TDi) and baseline activation (BLa): Controlling signal transduction when endogenous cytokines are ruining your differentiation Review
| Author: | Hackland, J. |
| Review Title: | Top-down inhibition (TDi) and baseline activation (BLa): Controlling signal transduction when endogenous cytokines are ruining your differentiation |
| Abstract: | In the 20 years since the first human pluripotent stem cell (hPSC) lines were established, there have been a plethora of protocols developed that allow us to generate a wide range of human cell types in vitro. Efforts to achieve a greater degree of specificity and efficiency in generating desired cell types have resulted in increasingly complex approaches. The magnitude and timing of signals has become key, and the concept of a “fully defined” system is a forever sought-after goal with shifting goalposts. This overview discusses two related approaches that can be used to deliver a tightly regulated, intermediate-strength signal, and which can also manage the impact of endogenous signaling variation and enable a switch away from bovine serum albumin–containing medium to a better-defined system without suffering a subsequent loss of robustness or efficiency. The approaches, referred to as top-down inhibition and baseline activation, were developed to deliver intermediate levels of BMP and WNT signaling during neural crest induction from hPSC, but could be applied to a variety of other signals and differentiation systems. © 2019 by John Wiley & Sons, Inc. © 2019 John Wiley & Sons, Inc. |
| Keywords: | signal transduction; protein expression; unclassified drug; bone morphogenetic protein; cell differentiation; endothelium cell; cytokine; regulatory mechanism; bovine serum albumin; neural crest; pluripotent stem cell; bone morphogenetic protein 2; beta catenin; wnt protein; positive feedback; wnt signaling; dickkopf 1 protein; tdi; human pluripotent stem cells; hemangioblast; bmp signaling; human; priority journal; article; recombinant bone morphogenetic protein 4; human pluripotent stem cell; 6 [[2 [[4 (2,4 dichlorophenyl) 5 (4 methyl 1h imidazol 2 yl) 2 pyrimidinyl]amino]ethyl]amino]nicotinonitrile; serum-free; baseline activation; bla; endogenous signaling; fully defined; hpsc; top-down inhibition; dmh1; dorsomorphin; cardiac endothelial cell; cardiac muscle cell; top down inhibition |
| Journal Title: | Current Protocols in Stem Cell Biology |
| Volume: | 51 |
| Issue: | 1 |
| ISSN: | 1941-7322 |
| Publisher: | John Wiley & Sons |
| Date Published: | 2019-12-01 |
| Start Page: | e98 |
| Language: | English |
| DOI: | 10.1002/cpsc.98 |
| PUBMED: | 31756052 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Article -- Export Date: 2 December 2019 -- Source: Scopus |
