Lineage-Specific Differentiation Is Influenced by State of Human Pluripotency
Jong-Hee Lee,
Sarah Laronde,
Tony J. Collins,
Zoya Shapovalova,
Borko Tanasijevic,
Jamie D. McNicol,
Aline Fiebig-Comyn,
Yannick D. Benoit,
Jung Bok Lee,
Ryan R. Mitchell,
Mickie Bhatia
Affiliations
Jong-Hee Lee
McMaster Stem Cell and Cancer Research Institute, Faculty of Health Sciences, McMaster University, 1280 Main Street West, MDCL 5029, Hamilton, ON L8S 4K1, Canada
Sarah Laronde
McMaster Stem Cell and Cancer Research Institute, Faculty of Health Sciences, McMaster University, 1280 Main Street West, MDCL 5029, Hamilton, ON L8S 4K1, Canada
Tony J. Collins
McMaster Stem Cell and Cancer Research Institute, Faculty of Health Sciences, McMaster University, 1280 Main Street West, MDCL 5029, Hamilton, ON L8S 4K1, Canada
Zoya Shapovalova
McMaster Stem Cell and Cancer Research Institute, Faculty of Health Sciences, McMaster University, 1280 Main Street West, MDCL 5029, Hamilton, ON L8S 4K1, Canada
Borko Tanasijevic
McMaster Stem Cell and Cancer Research Institute, Faculty of Health Sciences, McMaster University, 1280 Main Street West, MDCL 5029, Hamilton, ON L8S 4K1, Canada
Jamie D. McNicol
McMaster Stem Cell and Cancer Research Institute, Faculty of Health Sciences, McMaster University, 1280 Main Street West, MDCL 5029, Hamilton, ON L8S 4K1, Canada
Aline Fiebig-Comyn
McMaster Stem Cell and Cancer Research Institute, Faculty of Health Sciences, McMaster University, 1280 Main Street West, MDCL 5029, Hamilton, ON L8S 4K1, Canada
Yannick D. Benoit
McMaster Stem Cell and Cancer Research Institute, Faculty of Health Sciences, McMaster University, 1280 Main Street West, MDCL 5029, Hamilton, ON L8S 4K1, Canada
Jung Bok Lee
McMaster Stem Cell and Cancer Research Institute, Faculty of Health Sciences, McMaster University, 1280 Main Street West, MDCL 5029, Hamilton, ON L8S 4K1, Canada
Ryan R. Mitchell
McMaster Stem Cell and Cancer Research Institute, Faculty of Health Sciences, McMaster University, 1280 Main Street West, MDCL 5029, Hamilton, ON L8S 4K1, Canada
Mickie Bhatia
McMaster Stem Cell and Cancer Research Institute, Faculty of Health Sciences, McMaster University, 1280 Main Street West, MDCL 5029, Hamilton, ON L8S 4K1, Canada
Human pluripotent stem cells (hPSCs) have been reported in naive and primed states. However, the ability to generate mature cell types remains the imperative property for utility of hPSCs. Here, we reveal that the naive state enhances self-renewal while restricting lineage differentiation in vitro to neural default fate. Molecular analyses indicate expression of multiple lineage-associated transcripts in naive hPSCs that failed to predict biased functional differentiation capacity. Naive hPSCs can be converted to primed state over long-term serial passage that permits recovery of multi-germ layer differentiation. Suppression of OCT4 but not NANOG allows immediate recovery directly from naive state. To this end, we identified chemical inhibitors of OCT4 that restore naive hPSC differentiation. Our study reveals unique cell-fate restrictions in human pluripotent states and provides an approach to overcome these barriers that harness both efficient naive hPSC growth while maintaining in vitro differentiation essential for hPSC applications.
