Identification of a LIF-Responsive, Replication-Competent Subpopulation of Human β Cells
| Autor: | Jennifer H. R. Kenty, Idil I. Aigha, Edwin A. Rosado-Olivieri, Douglas A. Melton |
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| Rok vydání: | 2020 |
| Předmět: |
Adult
CCAAT-Enhancer-Binding Protein-delta Male Pluripotent Stem Cells STAT3 Transcription Factor 0301 basic medicine Physiology Mice SCID Leukemia Inhibitory Factor Mice 03 medical and health sciences 0302 clinical medicine Downregulation and upregulation Mice Inbred NOD Animals Humans Beta (finance) Receptor STAT3 Molecular Biology Cells Cultured Aged Cell Proliferation B-Lymphocytes biology Chemistry Embryogenesis RNA Cell Biology Middle Aged Cell cycle Cell biology Mice Inbred C57BL 030104 developmental biology biology.protein Female Single-Cell Analysis Leukemia inhibitory factor 030217 neurology & neurosurgery |
| Zdroj: | Cell Metabolism. 31:327-338.e6 |
| ISSN: | 1550-4131 |
| Popis: | Summary The beta (β)-cell mass formed during embryogenesis is amplified by cell replication during fetal and early postnatal development. Thereafter, β cells become functionally mature, and their mass is maintained by a low rate of replication. For those few β cells that replicate in adult life, it is not known how replication is initiated nor whether this occurs in a specialized subset of β cells. We capitalized on a YAP overexpression system to induce replication of stem-cell-derived β cells and, by single-cell RNA sequencing, identified an upregulation of the leukemia inhibitory factor (LIF) pathway. Activation of the LIF pathway induces replication of human β cells in vitro and in vivo. The expression of the LIF receptor is restricted to a subset of transcriptionally distinct human β cells with increased proliferative capacity. This study delineates novel genetic networks that control the replication of LIF-responsive, replication-competent human β cells. |
| Databáze: | OpenAIRE |
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