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Chromatin establishes an immature version of neuronal protocadherin selection during the naive-to-primed conversion of pluripotent stem cells.
Almenar-Queralt, Angels; Merkurjev, Daria; Kim, Hong Sook; Navarro, Michael; Ma, Qi; Chaves, Rodrigo S; Allegue, Catarina; Driscoll, Shawn P; Chen, Andrew G; Kohlnhofer, Bridget; Fong, Lauren K; Woodruff, Grace; Mackintosh, Carlos; Bohaciakova, Dasa; Hruska-Plochan, Marian; Tadokoro, Takahiro; Young, Jessica E; El Hajj, Nady; Dittrich, Marcus; Marsala, Martin; Goldstein, Lawrence S B; Garcia-Bassets, Ivan.
Afiliação
  • Almenar-Queralt A; Department of Medicine, School of Medicine, University of California, San Diego, La Jolla, CA, USA. aalmenar@ucsd.edu.
  • Merkurjev D; Sanford Consortium for Regenerative Medicine, University of California, San Diego, La Jolla, CA, USA. aalmenar@ucsd.edu.
  • Kim HS; Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA, USA. aalmenar@ucsd.edu.
  • Navarro M; Department of Medicine, School of Medicine, University of California, San Diego, La Jolla, CA, USA.
  • Ma Q; Department of Statistics, University of California, Los Angeles, Los Angeles, CA, USA.
  • Chaves RS; Department of Medicine, School of Medicine, University of California, San Diego, La Jolla, CA, USA.
  • Allegue C; Department of Anesthesiology, University of California, San Diego, La Jolla, CA, USA.
  • Driscoll SP; Department of Medicine, School of Medicine, University of California, San Diego, La Jolla, CA, USA.
  • Chen AG; Sanford Consortium for Regenerative Medicine, University of California, San Diego, La Jolla, CA, USA.
  • Kohlnhofer B; Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA, USA.
  • Fong LK; Department of Medicine, School of Medicine, University of California, San Diego, La Jolla, CA, USA.
  • Woodruff G; Center for Research in Molecular Medicine and Chronic Diseases, Santiago de Compostela, Spain.
  • Mackintosh C; Salk Institute for Biological Studies, La Jolla, CA, USA.
  • Bohaciakova D; Sanford Consortium for Regenerative Medicine, University of California, San Diego, La Jolla, CA, USA.
  • Hruska-Plochan M; Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA, USA.
  • Tadokoro T; Sanford Consortium for Regenerative Medicine, University of California, San Diego, La Jolla, CA, USA.
  • Young JE; Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA, USA.
  • El Hajj N; Sanford Consortium for Regenerative Medicine, University of California, San Diego, La Jolla, CA, USA.
  • Dittrich M; Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA, USA.
  • Marsala M; Sanford Consortium for Regenerative Medicine, University of California, San Diego, La Jolla, CA, USA.
  • Goldstein LSB; Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA, USA.
  • Garcia-Bassets I; Department of Medicine, School of Medicine, University of California, San Diego, La Jolla, CA, USA.
Nat Genet ; 51(12): 1691-1701, 2019 12.
Article em En | MEDLINE | ID: mdl-31740836
ABSTRACT
In the mammalian genome, the clustered protocadherin (cPCDH) locus provides a paradigm for stochastic gene expression with the potential to generate a unique cPCDH combination in every neuron. Here we report a chromatin-based mechanism that emerges during the transition from the naive to the primed states of cell pluripotency and reduces, by orders of magnitude, the combinatorial potential in the human cPCDH locus. This mechanism selectively increases the frequency of stochastic selection of a small subset of cPCDH genes after neuronal differentiation in monolayers, 10-month-old cortical organoids and engrafted cells in the spinal cords of rats. Signs of these frequent selections can be observed in the brain throughout fetal development and disappear after birth, except in conditions of delayed maturation such as Down's syndrome. We therefore propose that a pattern of limited cPCDH-gene expression diversity is maintained while human neurons still retain fetal-like levels of maturation.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Cromatina / Caderinas / Síndrome de Down / Células-Tronco Pluripotentes Induzidas / Neurônios Limite: Adult / Animals / Humans / Middle aged Idioma: En Ano de publicação: 2019 Tipo de documento: Article
Texto completo
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Cromatina / Caderinas / Síndrome de Down / Células-Tronco Pluripotentes Induzidas / Neurônios Limite: Adult / Animals / Humans / Middle aged Idioma: En Ano de publicação: 2019 Tipo de documento: Article