Understanding human fetal pancreas development using subpopulation sorting, RNA sequencing and single-cell profiling

TY - JOUR

T1 - Understanding human fetal pancreas development using subpopulation sorting, RNA sequencing and single-cell profiling

AU - Ramond, Cyrille

AU - Beydag-Tasöz, Belin Selcen

AU - Azad, Ajuna

AU - van de Bunt, Martijn

AU - Petersen, Maja Borup Kjær

AU - Beer, Nicola L

AU - Glaser, Nicolas

AU - Berthault, Claire

AU - Gloyn, Anna L

AU - Hansson, Mattias

AU - McCarthy, Mark I

AU - Honoré, Christian

AU - Grapin-Botton, Anne

AU - Scharfmann, Raphael

N1 - © 2018. Published by The Company of Biologists Ltd.

PY - 2018/8

Y1 - 2018/8

N2 - To decipher the populations of cells present in the human fetal pancreas and their lineage relationships, we developed strategies to isolate pancreatic progenitors, endocrine progenitors and endocrine cells. Transcriptome analysis of the individual populations revealed a large degree of conservation among vertebrates in the drivers of gene expression changes that occur at different steps of differentiation, although notably, sometimes, different members of the same gene family are expressed. The transcriptome analysis establishes a resource to identify novel genes and pathways involved in human pancreas development. Single-cell profiling further captured intermediate stages of differentiation and enabled us to decipher the sequence of transcriptional events occurring during human endocrine differentiation. Furthermore, we evaluate how well individual pancreatic cells derived in vitro from human pluripotent stem cells mirror the natural process occurring in human fetuses. This comparison uncovers a few differences at the progenitor steps, a convergence at the steps of endocrine induction, and the current inability to fully resolve endocrine cell subtypes in vitro.

AB - To decipher the populations of cells present in the human fetal pancreas and their lineage relationships, we developed strategies to isolate pancreatic progenitors, endocrine progenitors and endocrine cells. Transcriptome analysis of the individual populations revealed a large degree of conservation among vertebrates in the drivers of gene expression changes that occur at different steps of differentiation, although notably, sometimes, different members of the same gene family are expressed. The transcriptome analysis establishes a resource to identify novel genes and pathways involved in human pancreas development. Single-cell profiling further captured intermediate stages of differentiation and enabled us to decipher the sequence of transcriptional events occurring during human endocrine differentiation. Furthermore, we evaluate how well individual pancreatic cells derived in vitro from human pluripotent stem cells mirror the natural process occurring in human fetuses. This comparison uncovers a few differences at the progenitor steps, a convergence at the steps of endocrine induction, and the current inability to fully resolve endocrine cell subtypes in vitro.

KW - Fetus/cytology

KW - Flow Cytometry

KW - Gene Expression Profiling

KW - Gene Expression Regulation, Developmental/physiology

KW - Humans

KW - Pancreas/cytology

KW - Pluripotent Stem Cells/metabolism

KW - Transcription, Genetic/physiology

U2 - 10.1242/dev.165480

DO - 10.1242/dev.165480

M3 - Journal article

C2 - 30042179

SN - 0950-1991

VL - 145

JO - Development

JF - Development

IS - 16

ER -