Growth Factor Independence-1 (Gfi1) Is Required for Pancreatic Acinar Unit Formation and Centroacinar Cell Differentiation

Xiaoling Qu, Pia Nyeng, Fan Xiao, Jorge Dorantes, Jan Jensen

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

Resumé

BACKGROUND & AIMS: The genetic specification of the compartmentalized pancreatic acinar/centroacinar unit is poorly understood. Growth factor independence-1 (Gfi1) is a zinc finger transcriptional repressor that regulates hematopoietic stem cell maintenance, pre-T-cell differentiation, formation of granulocytes, inner ear hair cells, and the development of secretory cell types in the intestine. As GFI1/Gfi1 is expressed in human and rodent pancreas, we characterized the potential function of Gfi1 in mouse pancreatic development. METHODS: Gfi1 knockout mice were analyzed at histological and molecular levels, including qRT-PCR, in situ hybridization, immunohistochemistry, and electron microscopy. RESULTS: Loss of Gfi1 impacted formation and structure of the pancreatic acinar/centroacinar unit. Histologic and ultrastructural analysis of Gfi1-null pancreas revealed specific defects at the level of pancreatic acinar cells as well as the centroacinar cells (CACs) in Gfi1-/- mice when compared with wild-type littermates. Pancreatic endocrine differentiation, islet architecture, and function were unaffected. Organ domain patterning and the formation of ductal cells occurred normally during the murine secondary transition (E13.5-E14.5) in the Gfi1-/- pancreas. However, at later gestational time points (E18.5), expression of cellular markers for CACs was substantially reduced in Gfi1-/- mice, corroborated by electron microscopy imaging of the acinar/centroacinar unit. The reduction in CACs was correlated with an exocrine organ defect. Postnatally, Gfi1 deficiency resulted in severe pancreatic acinar dysplasia, including loss of granulation, autolytic vacuolation, and a proliferative and apoptotic response. CONCLUSIONS: Gfi1 plays an important role in regulating the development of pancreatic CACs and the function of pancreatic acinar cells.
OriginalsprogEngelsk
TidsskriftCellular and molecular gastroenterology and hepatology
Vol/bind1
Udgave nummer2
Sider (fra-til)233–247
ISSN2352-345X
DOI
StatusUdgivet - 2015
Udgivet eksterntJa

Citer dette

Qu, Xiaoling ; Nyeng, Pia ; Xiao, Fan ; Dorantes, Jorge ; Jensen, Jan. / Growth Factor Independence-1 (Gfi1) Is Required for Pancreatic Acinar Unit Formation and Centroacinar Cell Differentiation. I: Cellular and molecular gastroenterology and hepatology. 2015 ; Bind 1, Nr. 2. s. 233–247.
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abstract = "BACKGROUND & AIMS: The genetic specification of the compartmentalized pancreatic acinar/centroacinar unit is poorly understood. Growth factor independence-1 (Gfi1) is a zinc finger transcriptional repressor that regulates hematopoietic stem cell maintenance, pre-T-cell differentiation, formation of granulocytes, inner ear hair cells, and the development of secretory cell types in the intestine. As GFI1/Gfi1 is expressed in human and rodent pancreas, we characterized the potential function of Gfi1 in mouse pancreatic development. METHODS: Gfi1 knockout mice were analyzed at histological and molecular levels, including qRT-PCR, in situ hybridization, immunohistochemistry, and electron microscopy. RESULTS: Loss of Gfi1 impacted formation and structure of the pancreatic acinar/centroacinar unit. Histologic and ultrastructural analysis of Gfi1-null pancreas revealed specific defects at the level of pancreatic acinar cells as well as the centroacinar cells (CACs) in Gfi1-/- mice when compared with wild-type littermates. Pancreatic endocrine differentiation, islet architecture, and function were unaffected. Organ domain patterning and the formation of ductal cells occurred normally during the murine secondary transition (E13.5-E14.5) in the Gfi1-/- pancreas. However, at later gestational time points (E18.5), expression of cellular markers for CACs was substantially reduced in Gfi1-/- mice, corroborated by electron microscopy imaging of the acinar/centroacinar unit. The reduction in CACs was correlated with an exocrine organ defect. Postnatally, Gfi1 deficiency resulted in severe pancreatic acinar dysplasia, including loss of granulation, autolytic vacuolation, and a proliferative and apoptotic response. CONCLUSIONS: Gfi1 plays an important role in regulating the development of pancreatic CACs and the function of pancreatic acinar cells.",
author = "Xiaoling Qu and Pia Nyeng and Fan Xiao and Jorge Dorantes and Jan Jensen",
year = "2015",
doi = "10.1016/j.jcmgh.2014.12.004",
language = "English",
volume = "1",
pages = "233–247",
journal = "Cellular and molecular gastroenterology and hepatology",
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Qu, X, Nyeng, P, Xiao, F, Dorantes, J & Jensen, J 2015, 'Growth Factor Independence-1 (Gfi1) Is Required for Pancreatic Acinar Unit Formation and Centroacinar Cell Differentiation', Cellular and molecular gastroenterology and hepatology, bind 1, nr. 2, s. 233–247. https://doi.org/10.1016/j.jcmgh.2014.12.004

Growth Factor Independence-1 (Gfi1) Is Required for Pancreatic Acinar Unit Formation and Centroacinar Cell Differentiation. / Qu, Xiaoling; Nyeng, Pia; Xiao, Fan; Dorantes, Jorge; Jensen, Jan.

I: Cellular and molecular gastroenterology and hepatology, Bind 1, Nr. 2, 2015, s. 233–247.

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

TY - JOUR

T1 - Growth Factor Independence-1 (Gfi1) Is Required for Pancreatic Acinar Unit Formation and Centroacinar Cell Differentiation

AU - Qu, Xiaoling

AU - Nyeng, Pia

AU - Xiao, Fan

AU - Dorantes, Jorge

AU - Jensen, Jan

PY - 2015

Y1 - 2015

N2 - BACKGROUND & AIMS: The genetic specification of the compartmentalized pancreatic acinar/centroacinar unit is poorly understood. Growth factor independence-1 (Gfi1) is a zinc finger transcriptional repressor that regulates hematopoietic stem cell maintenance, pre-T-cell differentiation, formation of granulocytes, inner ear hair cells, and the development of secretory cell types in the intestine. As GFI1/Gfi1 is expressed in human and rodent pancreas, we characterized the potential function of Gfi1 in mouse pancreatic development. METHODS: Gfi1 knockout mice were analyzed at histological and molecular levels, including qRT-PCR, in situ hybridization, immunohistochemistry, and electron microscopy. RESULTS: Loss of Gfi1 impacted formation and structure of the pancreatic acinar/centroacinar unit. Histologic and ultrastructural analysis of Gfi1-null pancreas revealed specific defects at the level of pancreatic acinar cells as well as the centroacinar cells (CACs) in Gfi1-/- mice when compared with wild-type littermates. Pancreatic endocrine differentiation, islet architecture, and function were unaffected. Organ domain patterning and the formation of ductal cells occurred normally during the murine secondary transition (E13.5-E14.5) in the Gfi1-/- pancreas. However, at later gestational time points (E18.5), expression of cellular markers for CACs was substantially reduced in Gfi1-/- mice, corroborated by electron microscopy imaging of the acinar/centroacinar unit. The reduction in CACs was correlated with an exocrine organ defect. Postnatally, Gfi1 deficiency resulted in severe pancreatic acinar dysplasia, including loss of granulation, autolytic vacuolation, and a proliferative and apoptotic response. CONCLUSIONS: Gfi1 plays an important role in regulating the development of pancreatic CACs and the function of pancreatic acinar cells.

AB - BACKGROUND & AIMS: The genetic specification of the compartmentalized pancreatic acinar/centroacinar unit is poorly understood. Growth factor independence-1 (Gfi1) is a zinc finger transcriptional repressor that regulates hematopoietic stem cell maintenance, pre-T-cell differentiation, formation of granulocytes, inner ear hair cells, and the development of secretory cell types in the intestine. As GFI1/Gfi1 is expressed in human and rodent pancreas, we characterized the potential function of Gfi1 in mouse pancreatic development. METHODS: Gfi1 knockout mice were analyzed at histological and molecular levels, including qRT-PCR, in situ hybridization, immunohistochemistry, and electron microscopy. RESULTS: Loss of Gfi1 impacted formation and structure of the pancreatic acinar/centroacinar unit. Histologic and ultrastructural analysis of Gfi1-null pancreas revealed specific defects at the level of pancreatic acinar cells as well as the centroacinar cells (CACs) in Gfi1-/- mice when compared with wild-type littermates. Pancreatic endocrine differentiation, islet architecture, and function were unaffected. Organ domain patterning and the formation of ductal cells occurred normally during the murine secondary transition (E13.5-E14.5) in the Gfi1-/- pancreas. However, at later gestational time points (E18.5), expression of cellular markers for CACs was substantially reduced in Gfi1-/- mice, corroborated by electron microscopy imaging of the acinar/centroacinar unit. The reduction in CACs was correlated with an exocrine organ defect. Postnatally, Gfi1 deficiency resulted in severe pancreatic acinar dysplasia, including loss of granulation, autolytic vacuolation, and a proliferative and apoptotic response. CONCLUSIONS: Gfi1 plays an important role in regulating the development of pancreatic CACs and the function of pancreatic acinar cells.

U2 - 10.1016/j.jcmgh.2014.12.004

DO - 10.1016/j.jcmgh.2014.12.004

M3 - Journal article

VL - 1

SP - 233

EP - 247

JO - Cellular and molecular gastroenterology and hepatology

JF - Cellular and molecular gastroenterology and hepatology

SN - 2352-345X

IS - 2

ER -

Qu X, Nyeng P, Xiao F, Dorantes J, Jensen J. Growth Factor Independence-1 (Gfi1) Is Required for Pancreatic Acinar Unit Formation and Centroacinar Cell Differentiation. Cellular and molecular gastroenterology and hepatology. 2015;1(2):233–247. https://doi.org/10.1016/j.jcmgh.2014.12.004

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