Summary of Study ST001377
This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, where it has been assigned Project ID PR000942. The data can be accessed directly via it's Project DOI: 10.21228/M8XM5C This work is supported by NIH grant, U2C- DK119886.
See: https://www.metabolomicsworkbench.org/about/howtocite.php
This study contains a large results data set and is not available in the mwTab file. It is only available for download via FTP as data file(s) here.
| Study ID | ST001377 |
| Study Title | Stirred suspension bioreactors maintain naïve pluripotency of human pluripotent stem cells (hPSCs) |
| Study Summary | Although cell therapies require large numbers of quality-controlled hPSCs, existing technologies are limited in their ability to efficiently grow and scale stem cells. We report here that cell-state conversion from primed-to-naïve pluripotency enhances the biomanufacturing of hPSCs. Naïve hPSCs exhibit superior growth kinetics and aggregate formation characteristics in stirred suspension bioreactors compared to their primed counterparts. Moreover, we demonstrate the role of the bioreactor mechanical environment in the maintenance of naïve pluripotency, through transcriptomic enrichment of mechano-sensing signaling for cells in the bioreactor along with a decrease in expression of lineage-specific and primed pluripotency hallmarks. Bioreactor-cultured, naïve hPSCs express epigenetic regulatory transcripts associated with naïve pluripotency, and display hallmarks of X-chromosome reactivation. They exhibit robust production of naïve pluripotency metabolites and display reduced expression of primed pluripotency cell surface markers. We also show that these cells retain the ability to undergo targeted differentiation into beating cardiomyocytes, hepatocytes, and neural rosettes. They additionally display faster kinetics of teratoma formation compared to their primed counterparts. Naïve bioreactor hPSCs also retain structurally stable chromosomes. Our research corroborates that converting hPSCs to the naïve state enhances hPSC manufacturing and indicates a potentially important role for the bioreactor’s mechanical environment in maintaining naïve pluripotency. |
| Institute | University of Calgary |
| Department | Biochemistry and Molecular Biology |
| Laboratory | Stem Cell Research |
| Last Name | Rohani |
| First Name | Leili |
| Address | 405J, 1919 University Drive, NW |
| leili.rohanisarvesta@ucalgary.ca | |
| Phone | +1 5879681647 |
| Submit Date | 2020-05-08 |
| Raw Data Available | Yes |
| Raw Data File Type(s) | raw(Thermo) |
| Analysis Type Detail | LC-MS |
| Release Date | 2020-07-20 |
| Release Version | 1 |
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Collection:
| Collection ID: | CO001446 |
| Collection Summary: | Extracellular metabolite dynamics was analyzed during primed to naïve conversion in the bioreactor. For this, the media of H1 hESCs in the bioreactor was gradually switched from mTESR1 to RSeT media within 6 days of culture (D2 to D6) and the media was collected every day for the analysis. For H9 hESCs, the extracellular metabolites were analyzed in the spent media of primed and established naïve (P5) hPSCs in the bioreactor, and the media of each primed or naïve hPSCs was collected at day four of bioreactor culture. |
| Sample Type: | Stem cells |
