Organ size is limited by the number of embryonic progenitor cells in the pancreas but not the liver

The determinants of vertebrate organ size are poorly understood, but the process is thought to depend heavily on growth factors and other environmental cues. In the blood and central nervous system, for example, organ mass is determined primarily by growth-factor-regulated cell proliferation and apo...

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Published inNature Vol. 445; no. 7130; pp. 886 - 891
Main Authors Stanger, Ben Z., Tanaka, Akemi J., Melton, Douglas A.
Format Journal Article
LanguageEnglish
Published London Nature Publishing Group UK 22.02.2007
Nature Publishing
Nature Publishing Group
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Abstract The determinants of vertebrate organ size are poorly understood, but the process is thought to depend heavily on growth factors and other environmental cues. In the blood and central nervous system, for example, organ mass is determined primarily by growth-factor-regulated cell proliferation and apoptosis to achieve a final target size. Here, we report that the size of the mouse pancreas is constrained by an intrinsic programme established early in development, one that is essentially not subject to growth compensation. Specifically, final pancreas size is limited by the size of the progenitor cell pool that is set aside in the developing pancreatic bud. By contrast, the size of the liver is not constrained by reductions in the progenitor cell pool. These findings show that progenitor cell number, independently of regulation by growth factors, can be a key determinant of organ size. One size fits all For many organs, including blood, liver and muscle, tissue or organ size can be adjusted for cell loss. But not for the pancreas. New work shows that pancreas size is fixed by the number of progenitors set aside during embryogenesis. Other organs such as lung, kidney and thymus may be similarly size-limited, and this may relate to an organ's capacity for regeneration.
AbstractList The determinants of vertebrate organ size are poorly understood, but the process is thought to depend heavily on growth factors and other environmental cues. In the blood and central nervous system, for example, organ mass is determined primarily by growth-factor-regulated cell proliferation and apoptosis to achieve a final target size. Here, we report that the size of the mouse pancreas is constrained by an intrinsic programme established early in development, one that is essentially not subject to growth compensation. Specifically, final pancreas size is limited by the size of the progenitor cell pool that is set aside in the developing pancreatic bud. By contrast, the size of the liver is not constrained by reductions in the progenitor cell pool. These findings show that progenitor cell number, independently of regulation by growth factors, can be a key determinant of organ size.
The determinants of vertebrate organ size are poorly understood, but the process is thought to depend heavily on growth factors and other environmental cues. In the blood and central nervous system, for example, organ mass is determined primarily by growth-factor-regulated cell proliferation and apoptosis to achieve a final target size. Here, we report that the size of the mouse pancreas is constrained by an intrinsic programme established early in development, one that is essentially not subject to growth compensation. Specifically, final pancreas size is limited by the size of the progenitor cell pool that is set aside in the developing pancreatic bud. By contrast, the size of the liver is not constrained by reductions in the progenitor cell pool. These findings show that progenitor cell number, independently of regulation by growth factors, can be a key determinant of organ size. [PUBLICATION ABSTRACT]
The determinants of vertebrate organ size are poorly understood, but the process is thought to depend heavily on growth factors and other environmental cues. In the blood and central nervous system, for example, organ mass is determined primarily by growth-factor-regulated cell proliferation and apoptosis to achieve a final target size. Here, we report that the size of the mouse pancreas is constrained by an intrinsic programme established early in development, one that is essentially not subject to growth compensation. Specifically, final pancreas size is limited by the size of the progenitor cell pool that is set aside in the developing pancreatic bud. By contrast, the size of the liver is not constrained by reductions in the progenitor cell pool. These findings show that progenitor cell number, independently of regulation by growth factors, can be a key determinant of organ size.The determinants of vertebrate organ size are poorly understood, but the process is thought to depend heavily on growth factors and other environmental cues. In the blood and central nervous system, for example, organ mass is determined primarily by growth-factor-regulated cell proliferation and apoptosis to achieve a final target size. Here, we report that the size of the mouse pancreas is constrained by an intrinsic programme established early in development, one that is essentially not subject to growth compensation. Specifically, final pancreas size is limited by the size of the progenitor cell pool that is set aside in the developing pancreatic bud. By contrast, the size of the liver is not constrained by reductions in the progenitor cell pool. These findings show that progenitor cell number, independently of regulation by growth factors, can be a key determinant of organ size.
The determinants of vertebrate organ size are poorly understood, but the process is thought to depend heavily on growth factors and other environmental cues. In the blood and central nervous system, for example, organ mass is determined primarily by growth-factor-regulated cell proliferation and apoptosis to achieve a final target size. Here, we report that the size of the mouse pancreas is constrained by an intrinsic programme established early in development, one that is essentially not subject to growth compensation. Specifically, final pancreas size is limited by the size of the progenitor cell pool that is set aside in the developing pancreatic bud. By contrast, the size of the liver is not constrained by reductions in the progenitor cell pool. These findings show that progenitor cell number, independently of regulation by growth factors, can be a key determinant of organ size. One size fits all For many organs, including blood, liver and muscle, tissue or organ size can be adjusted for cell loss. But not for the pancreas. New work shows that pancreas size is fixed by the number of progenitors set aside during embryogenesis. Other organs such as lung, kidney and thymus may be similarly size-limited, and this may relate to an organ's capacity for regeneration.
Audience Academic
Author Stanger, Ben Z.
Melton, Douglas A.
Tanaka, Akemi J.
Author_xml – sequence: 1
  givenname: Ben Z.
  surname: Stanger
  fullname: Stanger, Ben Z.
  email: bstanger@mail.med.upenn.edu
  organization: Department of Molecular and Cellular Biology, Harvard Stem Cell Institute, and Howard Hughes Medical Institute, Cambridge, Massachusetts 02138, USA, Gastrointestinal Unit, Massachusetts General Hospital, Boston, Massachusetts 02114, USA, Present address: Division of Gastroenterology and Abramson Family Cancer Research Institute, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA
– sequence: 2
  givenname: Akemi J.
  surname: Tanaka
  fullname: Tanaka, Akemi J.
  organization: Department of Molecular and Cellular Biology, Harvard Stem Cell Institute, and Howard Hughes Medical Institute, Cambridge, Massachusetts 02138, USA
– sequence: 3
  givenname: Douglas A.
  surname: Melton
  fullname: Melton, Douglas A.
  email: dmelton@harvard.edu
  organization: Department of Molecular and Cellular Biology, Harvard Stem Cell Institute, and Howard Hughes Medical Institute, Cambridge, Massachusetts 02138, USA
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https://www.ncbi.nlm.nih.gov/pubmed/17259975$$D View this record in MEDLINE/PubMed
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Snippet The determinants of vertebrate organ size are poorly understood, but the process is thought to depend heavily on growth factors and other environmental cues....
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SubjectTerms Animals
Apoptosis
Biological and medical sciences
Blastocyst - metabolism
Blood
Cell Count
Cell Death
Cell growth
Cellular biology
Central nervous system
Compensation
Embryology: invertebrates and vertebrates. Teratology
Embryonic Stem Cells - cytology
Female
Fundamental and applied biological sciences. Psychology
Growth factors
Homeodomain Proteins - genetics
Homeodomain Proteins - metabolism
Humanities and Social Sciences
Liver
Liver - anatomy & histology
Liver - cytology
Liver - embryology
Male
Mice
Molecular biology
multidisciplinary
Organ Size
Organogenesis. Fetal development
Organogenesis. Physiological fonctions
Pancreas
Pancreas - anatomy & histology
Pancreas - cytology
Pancreas - embryology
Physical growth
Rodents
Science
Science (multidisciplinary)
Size
Trans-Activators - deficiency
Trans-Activators - genetics
Trans-Activators - metabolism
Vertebrates
Title Organ size is limited by the number of embryonic progenitor cells in the pancreas but not the liver
URI https://link.springer.com/article/10.1038/nature05537
https://www.ncbi.nlm.nih.gov/pubmed/17259975
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Volume 445
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