Open AccessCend1 and Neurog2 efficiently reprogram human cortical astrocytes to neural precursor cells and induced-neurons
Author(s) -
Katerina Aravantinou-Fatorou,
Seyyedeh Vejdani,
Dimitra Thomaidou
Publication year - 2022
Publication title -
the international journal of developmental biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.837
H-Index - 103
eISSN - 1696-3547
pISSN - 0214-6282
DOI - 10.1387/ijdb.210148dt
Subject(s) - reprogramming , biology , neural stem cell , microbiology and biotechnology , progenitor cell , astrocyte , neurite , progenitor , stem cell , neuroscience , cell , central nervous system , genetics , in vitro
Direct reprogramming of glial cells into induced-neurons is a promising strategy for CNS repair after acute injury or neurodegenerative diseases. Grey matter astrocytes, which exhibit features of neural stem cells when activated, are an ideal cell source for direct neuronal conversion. Aim of the study is the investigation of the neuronal reprogramming capacity of CEND1 and/or Neurogenin-2 ( NEUROG2 ) upon their overexpression on primary human adult cortical astrocytes. Our data indicate that adult human cortical astrocytes can be directly reprogrammed by either CEND1 or NEUROG2 to cells with differentiated neuronal morphology, exhibiting long neurites and branched processes. Exploration of gene expression dynamics along the conversion process revealed that neuronal genes are significantly up-regulated while astrocytic genes are down-regulated. Differentiated induced-neurons (iNs) exhibit either GABAergic or glutamatergic/dopaminergic identity upon CEND1 and NEUROG2 overexpression respectively. Co-expression of CEND1 and NEUROG2 in double-transduced cultures induced elevated expression levels of neural progenitor/stem genes and appearance of highly proliferative spheres with neural progenitor cell (NPC) properties in culture.