Sensory Neurons Do Not Induce Motor Neuron Loss in a Human Stem Cell Model of Spinal Muscular Atrophy
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{"title"=>"Sensory neurons do not induce motor neuron loss in a human stem cell model of spinal muscular atrophy", "type"=>"journal", "authors"=>[{"first_name"=>"Andrew J.", "last_name"=>"Schwab", "scopus_author_id"=>"55889308300"}, {"first_name"=>"Allison D.", "last_name"=>"Ebert", "scopus_author_id"=>"12790107300"}], "year"=>2014, "source"=>"PLoS ONE", "identifiers"=>{"issn"=>"19326203", "pui"=>"373596139", "sgr"=>"84904700148", "doi"=>"10.1371/journal.pone.0103112", "scopus"=>"2-s2.0-84904700148", "isbn"=>"1932-6203", "pmid"=>"25054590"}, "id"=>"d8a13d77-0782-3658-ad25-08215bbb05c3", "abstract"=>"Spinal muscular atrophy (SMA) is an autosomal recessive disorder leading to paralysis and early death due to reduced SMN protein. It is unclear why there is such a profound motor neuron loss, but recent evidence from fly and mouse studies indicate that cells comprising the whole sensory-motor circuit may contribute to motor neuron dysfunction and loss. Here, we used induced pluripotent stem cells derived from SMA patients to test whether sensory neurons directly contribute to motor neuron loss. We generated sensory neurons from SMA induced pluripotent stem cells and found no difference in neuron generation or survival, although there was a reduced calcium response to depolarizing stimuli. Using co-culture of SMA induced pluripotent stem cell derived sensory neurons with control induced pluripotent stem cell derived motor neurons, we found no significant reduction in motor neuron number or glutamate transporter boutons on motor neuron cell bodies or neurites. We conclude that SMA sensory neurons do not overtly contribute to motor neuron loss in this human stem cell system.", "link"=>"http://www.mendeley.com/research/sensory-neurons-not-induce-motor-neuron-loss-human-stem-cell-model-spinal-muscular-atrophy", "reader_count"=>10, "reader_count_by_academic_status"=>{"Professor > Associate Professor"=>1, "Researcher"=>1, "Student > Ph. D. Student"=>4, "Student > Master"=>2, "Other"=>1, "Lecturer"=>1}, "reader_count_by_user_role"=>{"Professor > Associate Professor"=>1, "Researcher"=>1, "Student > Ph. D. Student"=>4, "Student > Master"=>2, "Other"=>1, "Lecturer"=>1}, "reader_count_by_subject_area"=>{"Biochemistry, Genetics and Molecular Biology"=>2, "Agricultural and Biological Sciences"=>5, "Medicine and Dentistry"=>1, "Neuroscience"=>1, "Physics and Astronomy"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>1}, "Neuroscience"=>{"Neuroscience"=>1}, "Physics and Astronomy"=>{"Physics and Astronomy"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>5}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>2}}, "reader_count_by_country"=>{"France"=>1}, "group_count"=>2}

Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/1606312"], "description"=>"<p>(A) Control and SMA iPSCs generate nociceptive neurons as indicated by NTRK1 (red) and Tuj1 (green). Nuclei are labeled with Hoechst nuclear dye (blue). (B) There was no difference in neuron differentiation between control and SMA iPSC cultures at either 4 or 6 weeks of differentiation. n.s. = not significant by ANOVA. Scale bar = 50 µm.</p>", "links"=>[], "tags"=>["cell biology", "Cellular types", "Animal cells", "stem cells", "Induced pluripotent stem cells", "neuroscience", "neurology", "Neurodegenerative diseases", "Motor neuron diseases", "nociceptive", "neurons", "sma"], "article_id"=>1115469, "categories"=>["Biological Sciences"], "users"=>["Andrew J. Schwab", "Allison D. Ebert"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0103112.g002", "stats"=>{"downloads"=>1, "page_views"=>9, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Generation_of_nociceptive_neurons_from_control_and_SMA_iPSCs_/1115469", "title"=>"Generation of nociceptive neurons from control and SMA iPSCs.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-07-23 03:18:07"}
  • {"files"=>["https://ndownloader.figshare.com/files/1606311"], "description"=>"<p>(A) Control and SMA iPSCs acquire a Tuj1+ (green)/peripherin+ (red) sensory neuron phenotype by 2 weeks of differentiation that remained consistent through 6 weeks of differentiation. Nuclei are labeled with Hoechst nuclear dye (blue). Quantification of the Tuj1+ population (B) and peripherin+ population (C) show no significant difference in neuronal differentiation efficiency between control and SMA iPSCs at any time point. (D) At 6 weeks of differentiation there was no difference in neurite length between control and SMA iPSC-derived sensory neurons. (E) Ratiometric live cell calcium imaging showed a significant reduction in calcium response to KCl depolarization in the SMA iPSC-derived sensory neurons at 2 weeks of differentiation compared to controls. Representative imaging traces of at least 30 individual cells are shown for (F) one control iPSC line and (G) one SMA iPSC line. KCl indicates the time at which the depolarizing stimulus was added to the cultures. n.s. = not significant by ANOVA (B and C) or by Student’s t-test (D). ***p = 0.0008 by Student’s t-test (E). Scale bar = 50 µm.</p>", "links"=>[], "tags"=>["cell biology", "Cellular types", "Animal cells", "stem cells", "Induced pluripotent stem cells", "neuroscience", "neurology", "Neurodegenerative diseases", "Motor neuron diseases", "sensory", "neurons", "sma"], "article_id"=>1115468, "categories"=>["Biological Sciences"], "users"=>["Andrew J. Schwab", "Allison D. Ebert"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0103112.g001", "stats"=>{"downloads"=>0, "page_views"=>1, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Consistent_generation_of_sensory_neurons_from_control_and_SMA_iPSCs_/1115468", "title"=>"Consistent generation of sensory neurons from control and SMA iPSCs.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-07-23 03:18:07"}
  • {"files"=>["https://ndownloader.figshare.com/files/1606316"], "description"=>"<p>(A) VGlut1+ puncta (green) can be identified on both the cell soma and neurites of SMI-32+ control iPSC-derived MNs (red), as indicated by white arrows regardless of being co-cultured with control or SMA iPSC-derived SNs. Nuclei are labeled with Hoechst nuclear dye (blue). There is a trend toward reduced VGlut1+ puncta on both the cell soma (B) and neurites (C) of control iPSC-derived MNs in the presence of SMA iPSC-derived SNs at 4, 6, and 8 weeks in co-culture, but this trend did not reach significance. n.s. = not significant by ANOVA or by Student’s t-test for each time point. Scale bar = 20µm.</p>", "links"=>[], "tags"=>["cell biology", "Cellular types", "Animal cells", "stem cells", "Induced pluripotent stem cells", "neuroscience", "neurology", "Neurodegenerative diseases", "Motor neuron diseases", "sma", "ipsc-derived", "sensory", "neurons", "induce", "afferent", "innervation", "weeks"], "article_id"=>1115473, "categories"=>["Biological Sciences"], "users"=>["Andrew J. Schwab", "Allison D. Ebert"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0103112.g006", "stats"=>{"downloads"=>3, "page_views"=>113, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_The_presence_of_SMA_iPSC_derived_sensory_neurons_SN_does_not_induce_loss_of_afferent_innervation_on_control_iPSC_derived_motor_neurons_MN_over_4_8211_8_weeks_in_culture_/1115473", "title"=>"The presence of SMA iPSC-derived sensory neurons (SN) does not induce loss of afferent innervation on control iPSC-derived motor neurons (MN) over 4–8 weeks in culture.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-07-23 03:18:07"}
  • {"files"=>["https://ndownloader.figshare.com/files/1606314"], "description"=>"<p>GFAP+ glial cells (green) are simultaneously generated during the sensory neuron differentiation in both control and SMA iPSC cultures. Nuclei are labeled with Hoechst nuclear dye (blue). Scale bar = 50 µm.</p>", "links"=>[], "tags"=>["cell biology", "Cellular types", "Animal cells", "stem cells", "Induced pluripotent stem cells", "neuroscience", "neurology", "Neurodegenerative diseases", "Motor neuron diseases", "glial", "cells", "sensory", "neuron"], "article_id"=>1115471, "categories"=>["Biological Sciences"], "users"=>["Andrew J. Schwab", "Allison D. Ebert"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0103112.g004", "stats"=>{"downloads"=>0, "page_views"=>1, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Peripheral_glial_cells_are_present_in_the_sensory_neuron_cultures_/1115471", "title"=>"Peripheral glial cells are present in the sensory neuron cultures.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-07-23 03:18:07"}
  • {"files"=>["https://ndownloader.figshare.com/files/1606315"], "description"=>"<p>(A) Co-culture of control iPSC-derived SMI-32+ (green) motor neurons (MN) with either SMA iPSC-derived peripherin+ (red) sensory neurons (SN) or control iPSC-derived peripherin+ (red) SNs does not induce motor neuron loss. Nuclei are labeled with Hoechst nuclear dye (blue). Quantification is shown in B and C. n.s. = not significant by ANOVA. Scale bar = 50 µm.</p>", "links"=>[], "tags"=>["cell biology", "Cellular types", "Animal cells", "stem cells", "Induced pluripotent stem cells", "neuroscience", "neurology", "Neurodegenerative diseases", "Motor neuron diseases", "sma", "ipsc-derived", "sensory", "neurons", "induce", "neuron", "weeks"], "article_id"=>1115472, "categories"=>["Biological Sciences"], "users"=>["Andrew J. Schwab", "Allison D. Ebert"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0103112.g005", "stats"=>{"downloads"=>6, "page_views"=>75, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_The_presence_of_SMA_iPSC_derived_sensory_neurons_does_not_induce_motor_neuron_loss_at_4_6_and_8_weeks_of_differentiation_/1115472", "title"=>"The presence of SMA iPSC-derived sensory neurons does not induce motor neuron loss at 4, 6, and 8 weeks of differentiation.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-07-23 03:18:07"}
  • {"files"=>["https://ndownloader.figshare.com/files/1606313"], "description"=>"<p>(A) Both control and SMA iPSCs generate proprioceptive neurons as indicated by parvalbumin (red) and Tuj1 (green). Nuclei are labeled with Hoechst nuclear dye (blue). (B) There was no difference in parvalbumin+neuron number between control and SMA iPSC cultures. n.s. = not significant by t-test. Scale bar = 20 µm.</p>", "links"=>[], "tags"=>["cell biology", "Cellular types", "Animal cells", "stem cells", "Induced pluripotent stem cells", "neuroscience", "neurology", "Neurodegenerative diseases", "Motor neuron diseases", "proprioceptive", "neurons", "sma", "ipscs", "weeks"], "article_id"=>1115470, "categories"=>["Biological Sciences"], "users"=>["Andrew J. Schwab", "Allison D. Ebert"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0103112.g003", "stats"=>{"downloads"=>2, "page_views"=>23, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Generation_of_proprioceptive_neurons_from_control_and_SMA_iPSCs_at_6_weeks_of_differentiation_/1115470", "title"=>"Generation of proprioceptive neurons from control and SMA iPSCs at 6 weeks of differentiation.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-07-23 03:18:07"}
  • {"files"=>["https://ndownloader.figshare.com/files/1606317", "https://ndownloader.figshare.com/files/1606318", "https://ndownloader.figshare.com/files/1606319"], "description"=>"<div><p>Spinal muscular atrophy (SMA) is an autosomal recessive disorder leading to paralysis and early death due to reduced SMN protein. It is unclear why there is such a profound motor neuron loss, but recent evidence from fly and mouse studies indicate that cells comprising the whole sensory-motor circuit may contribute to motor neuron dysfunction and loss. Here, we used induced pluripotent stem cells derived from SMA patients to test whether sensory neurons directly contribute to motor neuron loss. We generated sensory neurons from SMA induced pluripotent stem cells and found no difference in neuron generation or survival, although there was a reduced calcium response to depolarizing stimuli. Using co-culture of SMA induced pluripotent stem cell derived sensory neurons with control induced pluripotent stem cell derived motor neurons, we found no significant reduction in motor neuron number or glutamate transporter boutons on motor neuron cell bodies or neurites. We conclude that SMA sensory neurons do not overtly contribute to motor neuron loss in this human stem cell system.</p></div>", "links"=>[], "tags"=>["cell biology", "Cellular types", "Animal cells", "stem cells", "Induced pluripotent stem cells", "neuroscience", "neurology", "Neurodegenerative diseases", "Motor neuron diseases", "neurons", "induce", "neuron", "spinal", "muscular"], "article_id"=>1115474, "categories"=>["Biological Sciences"], "users"=>["Andrew J. Schwab", "Allison D. Ebert"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0103112.s001", "https://dx.doi.org/10.1371/journal.pone.0103112.s002", "https://dx.doi.org/10.1371/journal.pone.0103112.s003"], "stats"=>{"downloads"=>2, "page_views"=>10, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Sensory_Neurons_Do_Not_Induce_Motor_Neuron_Loss_in_a_Human_Stem_Cell_Model_of_Spinal_Muscular_Atrophy_/1115474", "title"=>"Sensory Neurons Do Not Induce Motor Neuron Loss in a Human Stem Cell Model of Spinal Muscular Atrophy", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2014-07-23 03:18:07"}

PMC Usage Stats | Further Information

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Relative Metric

{"start_date"=>"2014-01-01T00:00:00Z", "end_date"=>"2014-12-31T00:00:00Z", "subject_areas"=>[{"subject_area"=>"/Biology and life sciences/Developmental biology", "average_usage"=>[285]}, {"subject_area"=>"/Biology and life sciences/Neuroscience", "average_usage"=>[289]}]}
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