Your browser doesn't support javascript.
loading
A specialized population of Periostin-expressing cardiac fibroblasts contributes to postnatal cardiomyocyte maturation and innervation.
Hortells, Luis; Valiente-Alandi, Iñigo; Thomas, Zachary M; Agnew, Emma J; Schnell, Dan J; York, Allen J; Vagnozzi, Ronald J; Meyer, Evan C; Molkentin, Jeffery D; Yutzey, Katherine E.
Afiliação
  • Hortells L; The Heart Institute, Division of Molecular Cardiovascular Biology, Cincinnati Children's Hospital Medical Center, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH 45267.
  • Valiente-Alandi I; The Heart Institute, Division of Molecular Cardiovascular Biology, Cincinnati Children's Hospital Medical Center, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH 45267.
  • Thomas ZM; Conservation Genetics, Institute for Conservation Research, San Diego Zoo, San Diego, CA 92101.
  • Agnew EJ; The Heart Institute, Division of Molecular Cardiovascular Biology, Cincinnati Children's Hospital Medical Center, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH 45267.
  • Schnell DJ; The Heart Institute, Division of Molecular Cardiovascular Biology, Cincinnati Children's Hospital Medical Center, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH 45267.
  • York AJ; Division of Biomedical Informatics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229.
  • Vagnozzi RJ; The Heart Institute, Division of Molecular Cardiovascular Biology, Cincinnati Children's Hospital Medical Center, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH 45267.
  • Meyer EC; The Heart Institute, Division of Molecular Cardiovascular Biology, Cincinnati Children's Hospital Medical Center, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH 45267.
  • Molkentin JD; The Confocal Imaging Core, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229.
  • Yutzey KE; The Heart Institute, Division of Molecular Cardiovascular Biology, Cincinnati Children's Hospital Medical Center, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH 45267.
Proc Natl Acad Sci U S A ; 117(35): 21469-21479, 2020 09 01.
Article em En | MEDLINE | ID: mdl-32817558
During the postnatal period in mammals, the cardiac muscle transitions from hyperplasic to hypertrophic growth, the extracellular matrix (ECM) undergoes remodeling, and the heart loses regenerative capacity. While ECM maturation and crosstalk between cardiac fibroblasts (CFs) and cardiomyocytes (CMs) have been implicated in neonatal heart development, not much is known about specialized fibroblast heterogeneity and function in the early postnatal period. In order to better understand CF functions in heart maturation and postnatal cardiomyocyte cell-cycle arrest, we have performed gene expression profiling and ablation of postnatal CF populations. Fibroblast lineages expressing Tcf21 or Periostin were traced in transgenic GFP reporter mice, and their biological functions and transitions during the postnatal period were examined in sorted cells using RNA sequencing. Highly proliferative Periostin (Postn)+ lineage CFs were found from postnatal day 1 (P1) to P11 but were not detected at P30, due to a repression of Postn gene expression. This population was less abundant and transcriptionally different from Tcf21+ resident CFs. The specialized Postn+ population preferentially expresses genes related to cell proliferation and neuronal development, while Tcf21+ CFs differentially express genes related to ECM maturation at P7 and immune crosstalk at P30. Ablation of the Postn+ CFs from P0 to P6 led to altered cardiac sympathetic nerve patterning and a reduction in binucleation and hypertrophic growth with increased fetal troponin (TroponinI1) expression in CM. Thus, postnatal CFs are heterogeneous and include a transient proliferative Postn+ population required for cardiac nerve development and cardiomyocyte maturation soon after birth.
Assuntos
Palavras-chave

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Limite: Animals Idioma: En Ano de publicação: 2020 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Limite: Animals Idioma: En Ano de publicação: 2020 Tipo de documento: Article