Establishing cell-intrinsic limitations in cell cycle progression controls graft growth and promotes differentiation of pancreatic endocrine cells
Robin S. Goland,
Posted 14 Mar 2020
bioRxiv DOI: 10.1101/2020.03.13.990812
Posted 14 Mar 2020
Beta cells have a low proliferative potential, which limits regeneration, but how these limitations are established is largely unknown. Understanding proliferation potential is important for the safty of cell replacement therapy with cell products made from stem cell with unlimited proliferative potential. Here we test a novel hypothesis, that these limitations are established through limitations in S-phase progression. We exposed differentiating stem cells to small molecules that interfere with cell cycle progression either by inducing G1 arrest, impairing S-phase entry, or S-phase completion. Upon release from these molecules, we determined growth potential, differentiation and function of insulin-producing cells in vitro and in vivo. We found that the combination of G1 arrest with a compromised DNA replication completion promoted the differentiation of progenitor cells towards insulin-producing cells, improved the stability of the differentiated state, and protected mice from diabetes without formation of cystic growths. Therefore, a compromised ability to enter S-phase and replicate the genome is a functionally important property of pancreatic endocrine differentiation, and can be exploited to generate insulin-producing organoids with predictable growth potential.
- Downloaded 449 times
- Download rankings, all-time:
- Site-wide: 75,453
- In cell biology: 3,423
- Year to date:
- Site-wide: 60,772
- Since beginning of last month:
- Site-wide: 54,823
Downloads over time
Distribution of downloads per paper, site-wide
- 27 Nov 2020: The website and API now include results pulled from medRxiv as well as bioRxiv.
- 18 Dec 2019: We're pleased to announce PanLingua, a new tool that enables you to search for machine-translated bioRxiv preprints using more than 100 different languages.
- 21 May 2019: PLOS Biology has published a community page about Rxivist.org and its design.
- 10 May 2019: The paper analyzing the Rxivist dataset has been published at eLife.
- 1 Mar 2019: We now have summary statistics about bioRxiv downloads and submissions.
- 8 Feb 2019: Data from Altmetric is now available on the Rxivist details page for every preprint. Look for the "donut" under the download metrics.
- 30 Jan 2019: preLights has featured the Rxivist preprint and written about our findings.
- 22 Jan 2019: Nature just published an article about Rxivist and our data.
- 13 Jan 2019: The Rxivist preprint is live!