An Engineered Mouse to Identify Proliferating Cells and Their Derivatives

BackgroundCell proliferation is a fundamental event during development, disease, and regeneration. Effectively tracking and quantifying proliferating cells and their derivatives is critical for addressing many research questions. Cell cycle expression such as for Ki67, proliferating cell nuclear ant...

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Main Authors: Jihyun Jang, Kurt A. Engleka, Feiyan Liu, Li Li, Guang Song, Jonathan A. Epstein, Deqiang Li
Format: Article
Language:English
Published: Frontiers Media S.A. 2020-05-01
Series:Frontiers in Cell and Developmental Biology
Subjects:
Online Access:https://www.frontiersin.org/article/10.3389/fcell.2020.00388/full
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author Jihyun Jang
Kurt A. Engleka
Kurt A. Engleka
Feiyan Liu
Feiyan Liu
Li Li
Guang Song
Jonathan A. Epstein
Jonathan A. Epstein
Deqiang Li
author_facet Jihyun Jang
Kurt A. Engleka
Kurt A. Engleka
Feiyan Liu
Feiyan Liu
Li Li
Guang Song
Jonathan A. Epstein
Jonathan A. Epstein
Deqiang Li
author_sort Jihyun Jang
collection DOAJ
description BackgroundCell proliferation is a fundamental event during development, disease, and regeneration. Effectively tracking and quantifying proliferating cells and their derivatives is critical for addressing many research questions. Cell cycle expression such as for Ki67, proliferating cell nuclear antigen (PCNA), or aurora kinase B (Aurkb), or measurement of 5-bromo-2′-deoxyuridine (BrdU) or 3H-thymidine incorporation have been widely used to assess and quantify cell proliferation. These are powerful tools for detecting actively proliferating cells, but they do not identify cell populations derived from proliferating progenitors over time.AimsWe developed a new mouse tool for lineage tracing of proliferating cells by targeting the Aurkb allele.ResultsIn quiescent cells or cells arrested at G1/S, little or no Aurkb mRNA is detectable. In cycling cells, Aurkb transcripts are detectable at G2 and become undetectable by telophase. These findings suggest that Aurkb transcription is restricted to proliferating cells and is tightly coupled to cell proliferation. Accordingly, we generated an AurkbER Cre/+ mouse by targeting a tamoxifen inducible Cre cassette into the start codon of Aurkb. We find that the AurkbER Cre/+ mouse faithfully labels proliferating cells in developing embryos and regenerative adult tissues such as intestine but does not label quiescent cells such as post-mitotic neurons.ConclusionThe AurkbER Cre/+ mouse faithfully labels proliferating cells and their derivatives in developing embryos and regenerative adult tissues. This new mouse tool provides a novel genetic tracing capability for studying tissue proliferation and regeneration.
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spelling doaj.art-3ffe2d65f17445419c29decd5ee4a9d02022-12-21T23:02:01ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2020-05-01810.3389/fcell.2020.00388535216An Engineered Mouse to Identify Proliferating Cells and Their DerivativesJihyun Jang0Kurt A. Engleka1Kurt A. Engleka2Feiyan Liu3Feiyan Liu4Li Li5Guang Song6Jonathan A. Epstein7Jonathan A. Epstein8Deqiang Li9Department of Surgery, Center for Vascular and Inflammatory Diseases, University of Maryland School of Medicine, Baltimore, MD, United StatesDepartment of Cell and Developmental Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United StatesPenn Cardiovascular Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United StatesDepartment of Cell and Developmental Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United StatesPenn Cardiovascular Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United StatesPenn Cardiovascular Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United StatesDepartment of Surgery, Center for Vascular and Inflammatory Diseases, University of Maryland School of Medicine, Baltimore, MD, United StatesDepartment of Cell and Developmental Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United StatesPenn Cardiovascular Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United StatesDepartment of Surgery, Center for Vascular and Inflammatory Diseases, University of Maryland School of Medicine, Baltimore, MD, United StatesBackgroundCell proliferation is a fundamental event during development, disease, and regeneration. Effectively tracking and quantifying proliferating cells and their derivatives is critical for addressing many research questions. Cell cycle expression such as for Ki67, proliferating cell nuclear antigen (PCNA), or aurora kinase B (Aurkb), or measurement of 5-bromo-2′-deoxyuridine (BrdU) or 3H-thymidine incorporation have been widely used to assess and quantify cell proliferation. These are powerful tools for detecting actively proliferating cells, but they do not identify cell populations derived from proliferating progenitors over time.AimsWe developed a new mouse tool for lineage tracing of proliferating cells by targeting the Aurkb allele.ResultsIn quiescent cells or cells arrested at G1/S, little or no Aurkb mRNA is detectable. In cycling cells, Aurkb transcripts are detectable at G2 and become undetectable by telophase. These findings suggest that Aurkb transcription is restricted to proliferating cells and is tightly coupled to cell proliferation. Accordingly, we generated an AurkbER Cre/+ mouse by targeting a tamoxifen inducible Cre cassette into the start codon of Aurkb. We find that the AurkbER Cre/+ mouse faithfully labels proliferating cells in developing embryos and regenerative adult tissues such as intestine but does not label quiescent cells such as post-mitotic neurons.ConclusionThe AurkbER Cre/+ mouse faithfully labels proliferating cells and their derivatives in developing embryos and regenerative adult tissues. This new mouse tool provides a novel genetic tracing capability for studying tissue proliferation and regeneration.https://www.frontiersin.org/article/10.3389/fcell.2020.00388/fullcell proliferationaurora kinase Bmouse modellineage tracingregenerationdevelopment
spellingShingle Jihyun Jang
Kurt A. Engleka
Kurt A. Engleka
Feiyan Liu
Feiyan Liu
Li Li
Guang Song
Jonathan A. Epstein
Jonathan A. Epstein
Deqiang Li
An Engineered Mouse to Identify Proliferating Cells and Their Derivatives
Frontiers in Cell and Developmental Biology
cell proliferation
aurora kinase B
mouse model
lineage tracing
regeneration
development
title An Engineered Mouse to Identify Proliferating Cells and Their Derivatives
title_full An Engineered Mouse to Identify Proliferating Cells and Their Derivatives
title_fullStr An Engineered Mouse to Identify Proliferating Cells and Their Derivatives
title_full_unstemmed An Engineered Mouse to Identify Proliferating Cells and Their Derivatives
title_short An Engineered Mouse to Identify Proliferating Cells and Their Derivatives
title_sort engineered mouse to identify proliferating cells and their derivatives
topic cell proliferation
aurora kinase B
mouse model
lineage tracing
regeneration
development
url https://www.frontiersin.org/article/10.3389/fcell.2020.00388/full
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