Pathways governing development of stem cell-derived pancreatic β cells: Lessons from embryogenesis

Sara Al-Khawaga, Bushra Memon, Alexandra E. Butler, Shahrad Taheri, Abdul B. Abou-Samra, Essam Mohamed

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

The loss of functional β cells leads to development of diabetes. Several studies have shown that β cells are specified through several stages of progenitors during pancreas development, each stage defined by the expression of specific transcription factors (TFs). Understanding signalling pathways that control the differentiation and specification processes during embryogenesis will facilitate efforts to obtain functional β cells in vitro. Our current knowledge of the mechanisms involved in pancreatic β cell development and survival under normal or diabetic conditions has come largely from animal studies. However, there are marked differences in islet structure and physiological properties between humans and animals, and not all phenotypes of human diabetes can be recapitulated in animal models. Therefore, human pluripotent stem cells (hPSCs), including human embryonic stem cells (hESCs) and human induced PSCs (hiPSCs) offer a great opportunity for increasing our understanding of the pathways regulating human pancreatic β-cell development and survival. Furthermore, hPSCs provide a renewable source of functional pancreatic β cells for cell replacement therapy as well as disease modelling. Herein, we discuss the signalling pathways involved in the development of pancreatic β cells during embryogenesis. Additionally, we describe how these pathways are manipulated in vitro to differentiate hPSCs into functional β cells. Finally, we highlight the progress that has been made for the applications of those cells in treating and modelling diabetes.

Original languageEnglish
JournalBiological Reviews
DOIs
Publication statusAccepted/In press - 1 Jan 2017

Fingerprint

Stem cells
Embryonic Development
stem cells
Stem Cells
embryogenesis
Medical problems
Animals
Pluripotent Stem Cells
cells
diabetes
Cell Survival
Transcription Factors
Specifications
Cell- and Tissue-Based Therapy
Pancreas
Animal Models
embryonic stem cells
pancreas
Phenotype
animals

Keywords

  • Development
  • Genes
  • HESCs
  • HiPSCs
  • Insulin-secreting cells
  • Pancreatic precursors
  • Transcription factors

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Pathways governing development of stem cell-derived pancreatic β cells : Lessons from embryogenesis. / Al-Khawaga, Sara; Memon, Bushra; Butler, Alexandra E.; Taheri, Shahrad; Abou-Samra, Abdul B.; Mohamed, Essam.

In: Biological Reviews, 01.01.2017.

Research output: Contribution to journalArticle

@article{036821c386a7471684f2b3d432289a4e,
title = "Pathways governing development of stem cell-derived pancreatic β cells: Lessons from embryogenesis",
abstract = "The loss of functional β cells leads to development of diabetes. Several studies have shown that β cells are specified through several stages of progenitors during pancreas development, each stage defined by the expression of specific transcription factors (TFs). Understanding signalling pathways that control the differentiation and specification processes during embryogenesis will facilitate efforts to obtain functional β cells in vitro. Our current knowledge of the mechanisms involved in pancreatic β cell development and survival under normal or diabetic conditions has come largely from animal studies. However, there are marked differences in islet structure and physiological properties between humans and animals, and not all phenotypes of human diabetes can be recapitulated in animal models. Therefore, human pluripotent stem cells (hPSCs), including human embryonic stem cells (hESCs) and human induced PSCs (hiPSCs) offer a great opportunity for increasing our understanding of the pathways regulating human pancreatic β-cell development and survival. Furthermore, hPSCs provide a renewable source of functional pancreatic β cells for cell replacement therapy as well as disease modelling. Herein, we discuss the signalling pathways involved in the development of pancreatic β cells during embryogenesis. Additionally, we describe how these pathways are manipulated in vitro to differentiate hPSCs into functional β cells. Finally, we highlight the progress that has been made for the applications of those cells in treating and modelling diabetes.",
keywords = "Development, Genes, HESCs, HiPSCs, Insulin-secreting cells, Pancreatic precursors, Transcription factors",
author = "Sara Al-Khawaga and Bushra Memon and Butler, {Alexandra E.} and Shahrad Taheri and Abou-Samra, {Abdul B.} and Essam Mohamed",
year = "2017",
month = "1",
day = "1",
doi = "10.1111/brv.12349",
language = "English",
journal = "Biological Reviews",
issn = "1464-7931",
publisher = "Wiley-Blackwell",

}

TY - JOUR

T1 - Pathways governing development of stem cell-derived pancreatic β cells

T2 - Lessons from embryogenesis

AU - Al-Khawaga, Sara

AU - Memon, Bushra

AU - Butler, Alexandra E.

AU - Taheri, Shahrad

AU - Abou-Samra, Abdul B.

AU - Mohamed, Essam

PY - 2017/1/1

Y1 - 2017/1/1

N2 - The loss of functional β cells leads to development of diabetes. Several studies have shown that β cells are specified through several stages of progenitors during pancreas development, each stage defined by the expression of specific transcription factors (TFs). Understanding signalling pathways that control the differentiation and specification processes during embryogenesis will facilitate efforts to obtain functional β cells in vitro. Our current knowledge of the mechanisms involved in pancreatic β cell development and survival under normal or diabetic conditions has come largely from animal studies. However, there are marked differences in islet structure and physiological properties between humans and animals, and not all phenotypes of human diabetes can be recapitulated in animal models. Therefore, human pluripotent stem cells (hPSCs), including human embryonic stem cells (hESCs) and human induced PSCs (hiPSCs) offer a great opportunity for increasing our understanding of the pathways regulating human pancreatic β-cell development and survival. Furthermore, hPSCs provide a renewable source of functional pancreatic β cells for cell replacement therapy as well as disease modelling. Herein, we discuss the signalling pathways involved in the development of pancreatic β cells during embryogenesis. Additionally, we describe how these pathways are manipulated in vitro to differentiate hPSCs into functional β cells. Finally, we highlight the progress that has been made for the applications of those cells in treating and modelling diabetes.

AB - The loss of functional β cells leads to development of diabetes. Several studies have shown that β cells are specified through several stages of progenitors during pancreas development, each stage defined by the expression of specific transcription factors (TFs). Understanding signalling pathways that control the differentiation and specification processes during embryogenesis will facilitate efforts to obtain functional β cells in vitro. Our current knowledge of the mechanisms involved in pancreatic β cell development and survival under normal or diabetic conditions has come largely from animal studies. However, there are marked differences in islet structure and physiological properties between humans and animals, and not all phenotypes of human diabetes can be recapitulated in animal models. Therefore, human pluripotent stem cells (hPSCs), including human embryonic stem cells (hESCs) and human induced PSCs (hiPSCs) offer a great opportunity for increasing our understanding of the pathways regulating human pancreatic β-cell development and survival. Furthermore, hPSCs provide a renewable source of functional pancreatic β cells for cell replacement therapy as well as disease modelling. Herein, we discuss the signalling pathways involved in the development of pancreatic β cells during embryogenesis. Additionally, we describe how these pathways are manipulated in vitro to differentiate hPSCs into functional β cells. Finally, we highlight the progress that has been made for the applications of those cells in treating and modelling diabetes.

KW - Development

KW - Genes

KW - HESCs

KW - HiPSCs

KW - Insulin-secreting cells

KW - Pancreatic precursors

KW - Transcription factors

UR - http://www.scopus.com/inward/record.url?scp=85021204301&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85021204301&partnerID=8YFLogxK

U2 - 10.1111/brv.12349

DO - 10.1111/brv.12349

M3 - Article

C2 - 28643455

AN - SCOPUS:85021204301

JO - Biological Reviews

JF - Biological Reviews

SN - 1464-7931

ER -