TY - JOUR
T1 - Astrocytes and neurons share region-specific transcriptional signatures that confer regional identity to neuronal reprogramming
AU - Herrero-Navarro, Alvaro
AU - Puche-Aroca, Lorenzo
AU - Moreno-Juan, Veronica
AU - Sempere-Ferràndez, Alejandro
AU - Espinosa, Ana
AU - Susín, Rafael
AU - Torres Masjoan, Laia
AU - Leyva-Díaz, Eduardo
AU - Karow, Marisa
AU - Figueres-Onate, Maria
AU - Lopez-Mascaraque, Laura
AU - López-Atalaya, Jose P
AU - Berninger, Benedikt
AU - López-Bendito, Guillermina
N1 - Publisher Copyright:
© 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution License 4.0 (CC BY).
PY - 2021/4/7
Y1 - 2021/4/7
N2 - Neural cell diversity is essential to endow distinct brain regions with specific functions. During development, progenitors within these regions are characterized by specific gene expression programs, contributing to the generation of diversity in postmitotic neurons and astrocytes. While the region-specific molecular diversity of neurons and astrocytes is increasingly understood, whether these cells share region-specific programs remains unknown. Here, we show that in the neocortex and thalamus, neurons and astrocytes express shared region-specific transcriptional and epigenetic signatures. These signatures not only distinguish cells across these two brain regions but are also detected across substructures within regions, such as distinct thalamic nuclei, where clonal analysis reveals the existence of common nucleus-specific progenitors for neurons and astrocytes. Consistent with their shared molecular signature, regional specificity is maintained following astrocyte-to-neuron reprogramming. A detailed understanding of these regional-specific signatures may thus inform strategies for future cell-based brain repair.
AB - Neural cell diversity is essential to endow distinct brain regions with specific functions. During development, progenitors within these regions are characterized by specific gene expression programs, contributing to the generation of diversity in postmitotic neurons and astrocytes. While the region-specific molecular diversity of neurons and astrocytes is increasingly understood, whether these cells share region-specific programs remains unknown. Here, we show that in the neocortex and thalamus, neurons and astrocytes express shared region-specific transcriptional and epigenetic signatures. These signatures not only distinguish cells across these two brain regions but are also detected across substructures within regions, such as distinct thalamic nuclei, where clonal analysis reveals the existence of common nucleus-specific progenitors for neurons and astrocytes. Consistent with their shared molecular signature, regional specificity is maintained following astrocyte-to-neuron reprogramming. A detailed understanding of these regional-specific signatures may thus inform strategies for future cell-based brain repair.
UR - http://www.scopus.com/inward/record.url?scp=85103995409&partnerID=8YFLogxK
U2 - 10.1126/sciadv.abe8978
DO - 10.1126/sciadv.abe8978
M3 - Article
SN - 2375-2548
VL - 7
JO - Science Advances
JF - Science Advances
IS - 15
M1 - eabe8978
ER -