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| Status |
Public on Sep 25, 2019 |
| Title |
Identification of a LIF-responsive replication-competent human β cell |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
The beta (β) cell mass formed during embryogenesis is amplified by cell replication that occurs primarily during fetal and early postnatal development. Thereafter, β cells become functionally mature and their mass is maintained by a very low rate of replication. For those few β cells that replicate in adult life, it is not known how replication is initiated, uncoupled from β cell function nor whether this occurs in a specialized subset of β cells. To explore these issues with the aim of controlling replication of mature human β cells, we capitalized on a YAP overexpression system that induces cell cycle re-entry in stem cell derived-β cells. Singe cell RNA sequencing revealed an upregulation of components of the leukemia inhibitory factor (LIF) pathway upon cell cycle re-entry. Experimental activation of the LIF pathway induces replication and expansion of human stem cell derived- and adult β cells in vitro and in vivo. In both stem cell derived- and adult human β cells, the expression of the LIF receptor LIFR is restricted to a subset of β cells with distinct transcriptional profiles and defines a subpopulation of β cells with increased replication rates. Further analysis identified 15 transcription factors whose gene networks are active in replicating β cells. Overall, this study sheds light on regulatory networks that control β cell replication and reveals a heterogeneity in LIF responsiveness and replication competence.
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| Overall design |
Single cell analysis of LacZ- and YAPS6A-overexpressing beta cells using the 10X genomics platform and bulk RNA-seq analysis of LIFR+ and LIFR- sorted beta cells.
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| Contributor(s) |
Rosado-Oliveri EA, Aigha II, Kenty JH, Swain D, Rivera-Feliciano J, Melton DA |
| Citation(s) |
31928884 |
| |
| Submission date |
Sep 24, 2019 |
| Last update date |
Jan 14, 2020 |
| Contact name |
Edwin Antonio Rosado-Olivieri |
| E-mail(s) |
erosadoolivieri@g.harvard.edu
|
| Organization name |
Harvard University
|
| Department |
Department of Stem Cell and Regenerative Biology
|
| Lab |
Melton lab
|
| Street address |
7 Divinity Ave
|
| City |
Cambridge |
| State/province |
MA |
| ZIP/Postal code |
02138 |
| Country |
USA |
| |
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| Platforms (1) |
| GPL18573 |
Illumina NextSeq 500 (Homo sapiens) |
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| Samples (14)
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| Relations |
| BioProject |
PRJNA573954 |
| SRA |
SRP223222 |
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