NKX6.1 transcription factor: a crucial regulator of pancreatic β cell development, identity, and proliferation

<p dir="ltr">Understanding the biology underlying the mechanisms and pathways regulating pancreatic β cell development is necessary to understand the pathology of diabetes mellitus (DM), which is characterized by the progressive reduction in insulin-producing β cell mass. Pluripotent...

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محفوظ في:
التفاصيل البيبلوغرافية
المؤلف الرئيسي: Idil I. Aigha (14913774) (author)
مؤلفون آخرون: Essam M. Abdelalim (5768072) (author)
منشور في: 2020
الموضوعات:
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author Idil I. Aigha (14913774)
author2 Essam M. Abdelalim (5768072)
author2_role author
author_facet Idil I. Aigha (14913774)
Essam M. Abdelalim (5768072)
author_role author
dc.creator.none.fl_str_mv Idil I. Aigha (14913774)
Essam M. Abdelalim (5768072)
dc.date.none.fl_str_mv 2020-10-01T00:00:00Z
dc.identifier.none.fl_str_mv 10.1186/s13287-020-01977-0
dc.relation.none.fl_str_mv https://figshare.com/articles/journal_contribution/NKX6_1_transcription_factor_a_crucial_regulator_of_pancreatic_cell_development_identity_and_proliferation/26114467
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
Medical biotechnology
Diabetes
Transcription factor
β cell mass
Pluripotent stem cells
Pancreatic progenitors
Cell therapy
dc.title.none.fl_str_mv NKX6.1 transcription factor: a crucial regulator of pancreatic β cell development, identity, and proliferation
dc.type.none.fl_str_mv Text
Journal contribution
info:eu-repo/semantics/publishedVersion
text
contribution to journal
description <p dir="ltr">Understanding the biology underlying the mechanisms and pathways regulating pancreatic β cell development is necessary to understand the pathology of diabetes mellitus (DM), which is characterized by the progressive reduction in insulin-producing β cell mass. Pluripotent stem cells (PSCs) can potentially offer an unlimited supply of functional β cells for cellular therapy and disease modeling of DM. Homeobox protein NKX6.1 is a transcription factor (TF) that plays a critical role in pancreatic β cell function and proliferation. In human pancreatic islet, NKX6.1 expression is exclusive to β cells and is undetectable in other islet cells. Several reports showed that activation of NKX6.1 in PSC-derived pancreatic progenitors (MPCs), expressing PDX1 (PDX1+/NKX6.1+), warrants their future commitment to monohormonal β cells. However, further differentiation of MPCs lacking NKX6.1 expression (PDX1+/NKX6.1−) results in an undesirable generation of non-functional polyhormonal β cells. The importance of NKX6.1 as a crucial regulator in MPC specification into functional β cells directs attentions to further investigating its mechanism and enhancing NKX6.1 expression as a means to increase β cell function and mass. Here, we shed light on the role of NKX6.1 during pancreatic β cell development and in directing the MPCs to functional monohormonal lineage. Furthermore, we address the transcriptional mechanisms and targets of NKX6.1 as well as its association with diabetes.</p><h2>Other Information</h2><p dir="ltr">Published in: Stem Cell Research & Therapy<br>License: <a href="http://creativecommons.org/licenses/by/4.0/" target="_blank">http://creativecommons.org/licenses/by/4.0/</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.1186/s13287-020-01977-0" target="_blank">https://dx.doi.org/10.1186/s13287-020-01977-0</a></p>
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network_acronym_str Manara2
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oai_identifier_str oai:figshare.com:article/26114467
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spelling NKX6.1 transcription factor: a crucial regulator of pancreatic β cell development, identity, and proliferationIdil I. Aigha (14913774)Essam M. Abdelalim (5768072)Biomedical and clinical sciencesClinical sciencesMedical biotechnologyDiabetesTranscription factorβ cell massPluripotent stem cellsPancreatic progenitorsCell therapy<p dir="ltr">Understanding the biology underlying the mechanisms and pathways regulating pancreatic β cell development is necessary to understand the pathology of diabetes mellitus (DM), which is characterized by the progressive reduction in insulin-producing β cell mass. Pluripotent stem cells (PSCs) can potentially offer an unlimited supply of functional β cells for cellular therapy and disease modeling of DM. Homeobox protein NKX6.1 is a transcription factor (TF) that plays a critical role in pancreatic β cell function and proliferation. In human pancreatic islet, NKX6.1 expression is exclusive to β cells and is undetectable in other islet cells. Several reports showed that activation of NKX6.1 in PSC-derived pancreatic progenitors (MPCs), expressing PDX1 (PDX1+/NKX6.1+), warrants their future commitment to monohormonal β cells. However, further differentiation of MPCs lacking NKX6.1 expression (PDX1+/NKX6.1−) results in an undesirable generation of non-functional polyhormonal β cells. The importance of NKX6.1 as a crucial regulator in MPC specification into functional β cells directs attentions to further investigating its mechanism and enhancing NKX6.1 expression as a means to increase β cell function and mass. Here, we shed light on the role of NKX6.1 during pancreatic β cell development and in directing the MPCs to functional monohormonal lineage. Furthermore, we address the transcriptional mechanisms and targets of NKX6.1 as well as its association with diabetes.</p><h2>Other Information</h2><p dir="ltr">Published in: Stem Cell Research & Therapy<br>License: <a href="http://creativecommons.org/licenses/by/4.0/" target="_blank">http://creativecommons.org/licenses/by/4.0/</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.1186/s13287-020-01977-0" target="_blank">https://dx.doi.org/10.1186/s13287-020-01977-0</a></p>2020-10-01T00:00:00ZTextJournal contributioninfo:eu-repo/semantics/publishedVersiontextcontribution to journal10.1186/s13287-020-01977-0https://figshare.com/articles/journal_contribution/NKX6_1_transcription_factor_a_crucial_regulator_of_pancreatic_cell_development_identity_and_proliferation/26114467CC BY 4.0info:eu-repo/semantics/openAccessoai:figshare.com:article/261144672020-10-01T00:00:00Z
spellingShingle NKX6.1 transcription factor: a crucial regulator of pancreatic β cell development, identity, and proliferation
Idil I. Aigha (14913774)
Biomedical and clinical sciences
Clinical sciences
Medical biotechnology
Diabetes
Transcription factor
β cell mass
Pluripotent stem cells
Pancreatic progenitors
Cell therapy
status_str publishedVersion
title NKX6.1 transcription factor: a crucial regulator of pancreatic β cell development, identity, and proliferation
title_full NKX6.1 transcription factor: a crucial regulator of pancreatic β cell development, identity, and proliferation
title_fullStr NKX6.1 transcription factor: a crucial regulator of pancreatic β cell development, identity, and proliferation
title_full_unstemmed NKX6.1 transcription factor: a crucial regulator of pancreatic β cell development, identity, and proliferation
title_short NKX6.1 transcription factor: a crucial regulator of pancreatic β cell development, identity, and proliferation
title_sort NKX6.1 transcription factor: a crucial regulator of pancreatic β cell development, identity, and proliferation
topic Biomedical and clinical sciences
Clinical sciences
Medical biotechnology
Diabetes
Transcription factor
β cell mass
Pluripotent stem cells
Pancreatic progenitors
Cell therapy