Identification of a LIF-Responsive, Replication-Competent Subpopulation of Human β Cells

Edwin A. Rosado-Olivieri, Idil I. Aigha, Jennifer H. Kenty, Douglas A. Melton

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Pages (from-to)327-338.e6
JournalCell Metabolism
Volume31
Issue number2
DOIs
StatePublished - Feb 4 2020

Keywords

  • beta cells
  • beta-cell regeneration
  • beta-cell replication
  • CEBPD
  • diabetes
  • LIF
  • single cell
  • STAT3

ASJC Scopus subject areas

  • Physiology
  • Molecular Biology
  • Cell Biology

Fingerprint

Dive into the research topics of 'Identification of a LIF-Responsive, Replication-Competent Subpopulation of Human β Cells'. Together they form a unique fingerprint.

Cite this