Characterization of Non-hormone Expressing Endocrine Cells in Fetal and Infant Human Pancreas

<h3>Context: </h3><p dir="ltr">Previously, we identified chromograninA positive hormone-negative (CPHN) cells in high frequency in human fetal and neonatal pancreas, likely representing nascent endocrine precursor cells. Here, we characterize the putative endocrine fate a...

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محفوظ في:
التفاصيل البيبلوغرافية
المؤلف الرئيسي: Abu Saleh Md Moin (6189512) (author)
مؤلفون آخرون: Chiara Montemurro (4375921) (author), Kylie Zeng (6189515) (author), Megan Cory (6189518) (author), Megan Nguyen (6189521) (author), Shweta Kulkarni (4023143) (author), Helga Fritsch (6189524) (author), Juris J. Meier (6189527) (author), Sangeeta Dhawan (6189530) (author), Robert A. Rizza (6189533) (author), Mark A. Atkinson (8608410) (author), Alexandra E. Butler (6189536) (author)
منشور في: 2019
الموضوعات:
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author Abu Saleh Md Moin (6189512)
author2 Chiara Montemurro (4375921)
Kylie Zeng (6189515)
Megan Cory (6189518)
Megan Nguyen (6189521)
Shweta Kulkarni (4023143)
Helga Fritsch (6189524)
Juris J. Meier (6189527)
Sangeeta Dhawan (6189530)
Robert A. Rizza (6189533)
Mark A. Atkinson (8608410)
Alexandra E. Butler (6189536)
author2_role author
author
author
author
author
author
author
author
author
author
author
author_facet Abu Saleh Md Moin (6189512)
Chiara Montemurro (4375921)
Kylie Zeng (6189515)
Megan Cory (6189518)
Megan Nguyen (6189521)
Shweta Kulkarni (4023143)
Helga Fritsch (6189524)
Juris J. Meier (6189527)
Sangeeta Dhawan (6189530)
Robert A. Rizza (6189533)
Mark A. Atkinson (8608410)
Alexandra E. Butler (6189536)
author_role author
dc.creator.none.fl_str_mv Abu Saleh Md Moin (6189512)
Chiara Montemurro (4375921)
Kylie Zeng (6189515)
Megan Cory (6189518)
Megan Nguyen (6189521)
Shweta Kulkarni (4023143)
Helga Fritsch (6189524)
Juris J. Meier (6189527)
Sangeeta Dhawan (6189530)
Robert A. Rizza (6189533)
Mark A. Atkinson (8608410)
Alexandra E. Butler (6189536)
dc.date.none.fl_str_mv 2019-01-09T03:00:00Z
dc.identifier.none.fl_str_mv 10.3389/fendo.2018.00791
dc.relation.none.fl_str_mv https://figshare.com/articles/journal_contribution/Characterization_of_Non-hormone_Expressing_Endocrine_Cells_in_Fetal_and_Infant_Human_Pancreas/25331206
dc.rights.none.fl_str_mv CC BY 4.0
info:eu-repo/semantics/openAccess
dc.subject.none.fl_str_mv Biomedical and clinical sciences
Clinical sciences
beta-cell
endocrine cells
development
maturation
transcription factor
replication
dc.title.none.fl_str_mv Characterization of Non-hormone Expressing Endocrine Cells in Fetal and Infant Human Pancreas
dc.type.none.fl_str_mv Text
Journal contribution
info:eu-repo/semantics/publishedVersion
text
contribution to journal
description <h3>Context: </h3><p dir="ltr">Previously, we identified chromograninA positive hormone-negative (CPHN) cells in high frequency in human fetal and neonatal pancreas, likely representing nascent endocrine precursor cells. Here, we characterize the putative endocrine fate and replicative status of these newly formed cells.</p><p dir="ltr"><br></p><h3>Objective: </h3><p dir="ltr">To establish the replicative frequency and transcriptional identity of CPHN cells, extending our observation on CPHN cell frequency to a larger cohort of fetal and infant pancreas.</p><p dir="ltr"><br></p><h3>Design, Setting, and Participants: </h3><p dir="ltr">8 fetal, 19 infant autopsy pancreata were evaluated for CPHN cell frequency; 12 fetal, 24 infant/child pancreata were evaluated for CPHN replication and identity.</p><p dir="ltr"><br></p><h3>Results: </h3><p dir="ltr">CPHN cell frequency decreased 84% (islets) and 42% (clusters) from fetal to infant life. Unlike the beta-cells at this stage, CPHN cells were rarely observed to replicate (0.2 ± 0.1 vs. 4.7 ± 1.0%, CPHN vs. islet hormone positive cell replication, p < 0.001), indicated by the lack of Ki67 expression in CPHN cells whether located in the islets or in small clusters, and with no detectable difference between fetal and infant groups. While the majority of CPHN cells express (in overall compartments of pancreas) the pan-endocrine transcription factor NKX2.2 and beta-cell specific NKX6.1 in comparable frequency in fetal and infant/child cases (81.9 ± 6.3 vs. 82.8 ± 3.8% NKX6.1+-CPHN cells of total CPHN cells, fetal vs. infant/child, p = 0.9; 88.0 ± 4.7 vs. 82.1 ± 5.3% NKX2.2+-CPHN cells of total CPHN cells, fetal vs. infant/child, p = 0.4), the frequency of clustered CPHN cells expressing NKX6.1 or NKX2.2 is lower in infant/child vs. fetal cases (1.2 ± 0.3 vs. 16.7 ± 4.7 clustered NKX6.1+-CPHN cells/mm2, infant/child vs. fetal, p < 0.01; 2.7 ± 1.0 vs. 16.0 ± 4.0 clustered NKX2.2+-CPHN cells/mm2, infant/child vs. fetal, p < 0.01).</p><p dir="ltr"><br></p><h3>Conclusions: </h3><p dir="ltr">The frequency of CPHN cells declines steeply from fetal to infant life, presumably as they differentiate to hormone-expressing cells. CPHN cells represent a non-replicative pool of endocrine precursor cells, a proportion of which are likely fated to become beta-cells.</p><p dir="ltr"><br></p><h3>Precis: </h3><p dir="ltr">CPHN cell frequency declines steeply from fetal to infant life, as they mature to hormone expression. CPHN cells represent a non-replicative pool of endocrine precursor cells, a proportion of which are likely fated to become beta-cells.</p><h2>Other Information</h2><p dir="ltr">Published in: Frontiers in Endocrinology<br>License: <a href="https://creativecommons.org/licenses/by/4.0/" target="_blank">https://creativecommons.org/licenses/by/4.0/</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.3389/fendo.2018.00791" target="_blank">https://dx.doi.org/10.3389/fendo.2018.00791</a></p>
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spelling Characterization of Non-hormone Expressing Endocrine Cells in Fetal and Infant Human PancreasAbu Saleh Md Moin (6189512)Chiara Montemurro (4375921)Kylie Zeng (6189515)Megan Cory (6189518)Megan Nguyen (6189521)Shweta Kulkarni (4023143)Helga Fritsch (6189524)Juris J. Meier (6189527)Sangeeta Dhawan (6189530)Robert A. Rizza (6189533)Mark A. Atkinson (8608410)Alexandra E. Butler (6189536)Biomedical and clinical sciencesClinical sciencesbeta-cellendocrine cellsdevelopmentmaturationtranscription factorreplication<h3>Context: </h3><p dir="ltr">Previously, we identified chromograninA positive hormone-negative (CPHN) cells in high frequency in human fetal and neonatal pancreas, likely representing nascent endocrine precursor cells. Here, we characterize the putative endocrine fate and replicative status of these newly formed cells.</p><p dir="ltr"><br></p><h3>Objective: </h3><p dir="ltr">To establish the replicative frequency and transcriptional identity of CPHN cells, extending our observation on CPHN cell frequency to a larger cohort of fetal and infant pancreas.</p><p dir="ltr"><br></p><h3>Design, Setting, and Participants: </h3><p dir="ltr">8 fetal, 19 infant autopsy pancreata were evaluated for CPHN cell frequency; 12 fetal, 24 infant/child pancreata were evaluated for CPHN replication and identity.</p><p dir="ltr"><br></p><h3>Results: </h3><p dir="ltr">CPHN cell frequency decreased 84% (islets) and 42% (clusters) from fetal to infant life. Unlike the beta-cells at this stage, CPHN cells were rarely observed to replicate (0.2 ± 0.1 vs. 4.7 ± 1.0%, CPHN vs. islet hormone positive cell replication, p < 0.001), indicated by the lack of Ki67 expression in CPHN cells whether located in the islets or in small clusters, and with no detectable difference between fetal and infant groups. While the majority of CPHN cells express (in overall compartments of pancreas) the pan-endocrine transcription factor NKX2.2 and beta-cell specific NKX6.1 in comparable frequency in fetal and infant/child cases (81.9 ± 6.3 vs. 82.8 ± 3.8% NKX6.1+-CPHN cells of total CPHN cells, fetal vs. infant/child, p = 0.9; 88.0 ± 4.7 vs. 82.1 ± 5.3% NKX2.2+-CPHN cells of total CPHN cells, fetal vs. infant/child, p = 0.4), the frequency of clustered CPHN cells expressing NKX6.1 or NKX2.2 is lower in infant/child vs. fetal cases (1.2 ± 0.3 vs. 16.7 ± 4.7 clustered NKX6.1+-CPHN cells/mm2, infant/child vs. fetal, p < 0.01; 2.7 ± 1.0 vs. 16.0 ± 4.0 clustered NKX2.2+-CPHN cells/mm2, infant/child vs. fetal, p < 0.01).</p><p dir="ltr"><br></p><h3>Conclusions: </h3><p dir="ltr">The frequency of CPHN cells declines steeply from fetal to infant life, presumably as they differentiate to hormone-expressing cells. CPHN cells represent a non-replicative pool of endocrine precursor cells, a proportion of which are likely fated to become beta-cells.</p><p dir="ltr"><br></p><h3>Precis: </h3><p dir="ltr">CPHN cell frequency declines steeply from fetal to infant life, as they mature to hormone expression. CPHN cells represent a non-replicative pool of endocrine precursor cells, a proportion of which are likely fated to become beta-cells.</p><h2>Other Information</h2><p dir="ltr">Published in: Frontiers in Endocrinology<br>License: <a href="https://creativecommons.org/licenses/by/4.0/" target="_blank">https://creativecommons.org/licenses/by/4.0/</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.3389/fendo.2018.00791" target="_blank">https://dx.doi.org/10.3389/fendo.2018.00791</a></p>2019-01-09T03:00:00ZTextJournal contributioninfo:eu-repo/semantics/publishedVersiontextcontribution to journal10.3389/fendo.2018.00791https://figshare.com/articles/journal_contribution/Characterization_of_Non-hormone_Expressing_Endocrine_Cells_in_Fetal_and_Infant_Human_Pancreas/25331206CC BY 4.0info:eu-repo/semantics/openAccessoai:figshare.com:article/253312062019-01-09T03:00:00Z
spellingShingle Characterization of Non-hormone Expressing Endocrine Cells in Fetal and Infant Human Pancreas
Abu Saleh Md Moin (6189512)
Biomedical and clinical sciences
Clinical sciences
beta-cell
endocrine cells
development
maturation
transcription factor
replication
status_str publishedVersion
title Characterization of Non-hormone Expressing Endocrine Cells in Fetal and Infant Human Pancreas
title_full Characterization of Non-hormone Expressing Endocrine Cells in Fetal and Infant Human Pancreas
title_fullStr Characterization of Non-hormone Expressing Endocrine Cells in Fetal and Infant Human Pancreas
title_full_unstemmed Characterization of Non-hormone Expressing Endocrine Cells in Fetal and Infant Human Pancreas
title_short Characterization of Non-hormone Expressing Endocrine Cells in Fetal and Infant Human Pancreas
title_sort Characterization of Non-hormone Expressing Endocrine Cells in Fetal and Infant Human Pancreas
topic Biomedical and clinical sciences
Clinical sciences
beta-cell
endocrine cells
development
maturation
transcription factor
replication