Toward the Beginning of Time: Circadian Rhythms in Metabolism Precede Rhythms in Clock Gene Expression in Mouse Embryonic Stem Cells
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{"title"=>"Toward the Beginning of Time: Circadian Rhythms in Metabolism Precede Rhythms in Clock Gene Expression in Mouse Embryonic Stem Cells", "type"=>"journal", "authors"=>[{"first_name"=>"Jiffin K.", "last_name"=>"Paulose", "scopus_author_id"=>"34067841400"}, {"first_name"=>"Edmund B.", "last_name"=>"Rucker", "scopus_author_id"=>"6603957209"}, {"first_name"=>"Vincent M.", "last_name"=>"Cassone", "scopus_author_id"=>"56687667700"}], "year"=>2012, "source"=>"PLoS ONE", "identifiers"=>{"pmid"=>"23155474", "doi"=>"10.1371/journal.pone.0049555", "sgr"=>"84869137280", "isbn"=>"1932-6203 (Electronic)\\r1932-6203 (Linking)", "scopus"=>"2-s2.0-84869137280", "issn"=>"19326203", "pui"=>"366053744"}, "id"=>"6e3ad4d2-4902-3dfa-ae32-060564bc4567", "abstract"=>"The appearance, progression, and potential role for circadian rhythms during early development have previously focused mainly on the suprachiasmatic nucleus (SCN) and peri- and postnatal expression of canonical clock genes. More recently, gene expression studies in embryonic stem cells have shown that some clock genes are expressed in undifferentiated cells; however rhythmicity was only established when cells are directed toward a neural fate. These studies also concluded that a functional clock is not present in ESCs, based solely on their gene expression. The null hypothesis underlying the present study is that embryonic stem cells become rhythmic in both clock gene expression and glucose utilization only when allowed to spontaneously differentiate. Undifferentiated stem cells (ESCs, n = 6 cultures/timepoint for all experiments) were either maintained in their pluripotent state or released into differentiation (dESCs, n = 6 cultures/timepoint for all experiments). Glucose utilization was assayed through 2-deoxyglucose uptake measurement, and clock gene and glucose transporter expression was assayed every 4 hours for 2 days in ESCs and dESCs by quantitative PCR (qPCR) in the same cell lysates. Undifferentiated stem cells expressed a self-sustained rhythm in glucose uptake that was not coincident with rhythmic expression of clock genes. This physiological rhythm was paralleled by glucose transporter mRNA expression. Upon differentiation, circadian patterns of some but not all clock genes were expressed, and the amplitude of the glucose utilization rhythm was enhanced in dESCs. These data provide the earliest evidence of a functional circadian clock, in addition to further challenging the idea that rhythmic transcription of clock genes are necessary for rhythmic physiological output and suggest a role for a clock-controlled physiology in the earliest stages of development.", "link"=>"http://www.mendeley.com/research/toward-beginning-time-circadian-rhythms-metabolism-precede-rhythms-clock-gene-expression-mouse-embry", "reader_count"=>61, "reader_count_by_academic_status"=>{"Unspecified"=>1, "Professor > Associate Professor"=>4, "Researcher"=>9, "Student > Doctoral Student"=>3, "Student > Ph. D. Student"=>20, "Student > Postgraduate"=>4, "Other"=>1, "Student > Master"=>4, "Student > Bachelor"=>11, "Lecturer"=>1, "Professor"=>3}, "reader_count_by_user_role"=>{"Unspecified"=>1, "Professor > Associate Professor"=>4, "Researcher"=>9, "Student > Doctoral Student"=>3, "Student > Ph. D. Student"=>20, "Student > Postgraduate"=>4, "Other"=>1, "Student > Master"=>4, "Student > Bachelor"=>11, "Lecturer"=>1, "Professor"=>3}, "reader_count_by_subject_area"=>{"Unspecified"=>3, "Biochemistry, Genetics and Molecular Biology"=>8, "Agricultural and Biological Sciences"=>40, "Medicine and Dentistry"=>4, "Neuroscience"=>3, "Chemistry"=>2, "Linguistics"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>4}, "Neuroscience"=>{"Neuroscience"=>3}, "Chemistry"=>{"Chemistry"=>2}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>40}, "Linguistics"=>{"Linguistics"=>1}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>8}, "Unspecified"=>{"Unspecified"=>3}}, "reader_count_by_country"=>{"United States"=>1, "Italy"=>1, "Portugal"=>1, "Germany"=>3}, "group_count"=>2}

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/543486"], "description"=>"<p>qPCR data comparing relative clock gene mRNA expression in ESCs (n = 6, white circles) and dESCs (n = 6, black circles). Comparisons of A) <i>mClock</i>, B) <i>mBmal1</i> and, C) <i>mRor-a</i>. Line segments connecting data points denote statistically rhythmic oscillations. Error bars indicate ± SEM.</p>", "links"=>[], "tags"=>["elements", "molecular", "arrhythmic", "detectable", "rhythmic"], "article_id"=>213981, "categories"=>["Molecular Biology", "Biochemistry", "Physiology", "Developmental Biology"], "users"=>["Jiffin K. Paulose", "Edmund B. Rucker III", "Vincent M. Cassone"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0049555.g003", "stats"=>{"downloads"=>1, "page_views"=>7, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Positive_elements_of_the_molecular_clock_are_arrhythmic_or_not_detectable_in_ESCs_but_some_are_rhythmic_in_dESCs_/213981", "title"=>"Positive elements of the molecular clock are arrhythmic or not detectable in ESCs, but some are rhythmic in dESCs.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-11-14 01:06:21"}
  • {"files"=>["https://ndownloader.figshare.com/files/543791"], "description"=>"<p>Baseline subtracted bioluminescence of mPER2::LUCIFERASE in A, Top Panel) ESCs and A, Bottom Panel) dESCs. B) Raw data of dESC bioluminescence. Arrows indicate media exchange.</p>", "links"=>[], "tags"=>["arrhythmic", "escs", "rhythmic"], "article_id"=>214282, "categories"=>["Molecular Biology", "Biochemistry", "Physiology", "Developmental Biology"], "users"=>["Jiffin K. Paulose", "Edmund B. Rucker III", "Vincent M. Cassone"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0049555.g005", "stats"=>{"downloads"=>8, "page_views"=>7, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_mPER2_protein_is_arrhythmic_in_ESCs_and_rhythmic_in_dESCs_/214282", "title"=>"mPER2 protein is arrhythmic in ESCs and rhythmic in dESCs.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-11-14 01:11:22"}
  • {"files"=>["https://ndownloader.figshare.com/files/543303"], "description"=>"<p>2-DG uptake as normalized to total RNA levels in ESCs (A, n = 6) and dESCs (B, n = 6). C) <i>mGlut8</i> mRNA expression is rhythmic in both ESCS (n = 6, white circles) and dESCs (n = 6, black circles). D) <i>mGlut1</i> expression was not rhythmic in either culture. Lines connecting scatter denote statistically rhythmic oscillations. Note that the ordinate axis is different in A than in B to better illustrate the low-amplitude rhythm in undifferentiated cells. Error bars indicate ± SEM.</p>", "links"=>[], "tags"=>["uptake", "glucose", "transporter", "rhythmic", "escs"], "article_id"=>213797, "categories"=>["Molecular Biology", "Biochemistry", "Physiology", "Developmental Biology"], "users"=>["Jiffin K. Paulose", "Edmund B. Rucker III", "Vincent M. Cassone"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0049555.g002", "stats"=>{"downloads"=>1, "page_views"=>2, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_2_DG_uptake_and_glucose_transporter_8_expression_are_rhythmic_in_ESCs_and_dESCs_/213797", "title"=>"2-DG uptake and glucose transporter 8 expression are rhythmic in ESCs and dESCs.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-11-14 01:03:17"}
  • {"files"=>["https://ndownloader.figshare.com/files/543575"], "description"=>"<p>Relative expression levels of A) <i>mPer1</i>, B) <i>mPer2</i>, C) <i>mCry1</i>, and D) <i>mReverb-a</i> mRNA in ESCs (n = 6, white circles) and dESCs (n = 6, black circles). Line segments connecting data points denote statistically rhythmic oscillations. Error bars indicate ± SEM.</p>", "links"=>[], "tags"=>["elements", "molecular", "arrhythmic", "rhythmic"], "article_id"=>214070, "categories"=>["Molecular Biology", "Biochemistry", "Physiology", "Developmental Biology"], "users"=>["Jiffin K. Paulose", "Edmund B. Rucker III", "Vincent M. Cassone"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0049555.g004", "stats"=>{"downloads"=>1, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Negative_elements_of_the_molecular_clock_are_arrhythmic_in_ESCs_but_most_are_rhythmic_in_dESCs_/214070", "title"=>"Negative elements of the molecular clock are arrhythmic in ESCs, but most are rhythmic in dESCs.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-11-14 01:07:50"}
  • {"files"=>["https://ndownloader.figshare.com/files/290952"], "description"=>"<div><p>The appearance, progression, and potential role for circadian rhythms during early development have previously focused mainly on the suprachiasmatic nucleus (SCN) and peri- and postnatal expression of canonical clock genes. More recently, gene expression studies in embryonic stem cells have shown that some clock genes are expressed in undifferentiated cells; however rhythmicity was only established when cells are directed toward a neural fate. These studies also concluded that a functional clock is not present in ESCs, based solely on their gene expression. The <em>null</em> hypothesis underlying the present study is that embryonic stem cells become rhythmic in both clock gene expression and glucose utilization only when allowed to spontaneously differentiate. Undifferentiated stem cells (ESCs, n = 6 cultures/timepoint for all experiments) were either maintained in their pluripotent state or released into differentiation (dESCs, n = 6 cultures/timepoint for all experiments). Glucose utilization was assayed through 2-deoxyglucose uptake measurement, and clock gene and glucose transporter expression was assayed every 4 hours for 2 days in ESCs and dESCs by quantitative PCR (qPCR) in the same cell lysates. Undifferentiated stem cells expressed a self-sustained rhythm in glucose uptake that was not coincident with rhythmic expression of clock genes. This physiological rhythm was paralleled by glucose transporter mRNA expression. Upon differentiation, circadian patterns of some but not all clock genes were expressed, and the amplitude of the glucose utilization rhythm was enhanced in dESCs. These data provide the earliest evidence of a functional circadian clock, in addition to further challenging the idea that rhythmic transcription of clock genes are necessary for rhythmic physiological output and suggest a role for a clock-controlled physiology in the earliest stages of development.</p> </div>", "links"=>[], "tags"=>["circadian", "rhythms", "metabolism", "precede", "embryonic", "cells"], "article_id"=>117284, "categories"=>["Molecular Biology", "Biochemistry", "Physiology", "Developmental Biology"], "users"=>["Jiffin K. Paulose", "Edmund B. Rucker III", "Vincent M. Cassone"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0049555", "stats"=>{"downloads"=>2, "page_views"=>10, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Toward_the_Beginning_of_Time_Circadian_Rhythms_in_Metabolism_Precede_Rhythms_in_Clock_Gene_Expression_in_Mouse_Embryonic_Stem_Cells__/117284", "title"=>"Toward the Beginning of Time: Circadian Rhythms in Metabolism Precede Rhythms in Clock Gene Expression in Mouse Embryonic Stem Cells", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2012-11-14 02:01:24"}
  • {"files"=>["https://ndownloader.figshare.com/files/543189"], "description"=>"<p>Relative expression levels of <i>mOct4</i> and photomicrographs of ESCs (A, n = 6 and A inset, respectively) and dESCs (B, n = 6 and B inset). Error bars indicate ± SEM.</p>", "links"=>[], "tags"=>["descs", "distinguishable", "morphology"], "article_id"=>213682, "categories"=>["Molecular Biology", "Biochemistry", "Physiology", "Developmental Biology"], "users"=>["Jiffin K. Paulose", "Edmund B. Rucker III", "Vincent M. Cassone"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0049555.g001", "stats"=>{"downloads"=>1, "page_views"=>12, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_ESCs_and_dESCs_are_distinguishable_by_morphology_and_mOct4_expression_/213682", "title"=>"ESCs and dESCs are distinguishable by morphology and <i>mOct4</i> expression.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-11-14 01:01:22"}

PMC Usage Stats | Further Information

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Relative Metric

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