Multiple origins and modularity in the spatiotemporal emergence of cerebellar astrocyte heterogeneity

PLoS Biol. 2018 Sep 27;16(9):e2005513. doi: 10.1371/journal.pbio.2005513. eCollection 2018 Sep.

Abstract

The morphological, molecular, and functional heterogeneity of astrocytes is under intense scrutiny, but how this diversity is ontogenetically achieved remains largely unknown. Here, by quantitative in vivo clonal analyses and proliferation studies, we demonstrate that the major cerebellar astrocyte types emerge according to an unprecedented and remarkably orderly developmental program comprising (i) a time-dependent decline in both clone size and progenitor multipotency, associated with clone allocation first to the hemispheres and then to the vermis(ii) distinctive clonal relationships among astrocyte types, revealing diverse lineage potentials of embryonic and postnatal progenitors; and (iii) stereotyped clone architectures and recurrent modularities that correlate to layer-specific dynamics of postnatal proliferation/differentiation. In silico simulations indicate that the sole presence of a unique multipotent progenitor at the source of the whole astrogliogenic program is unlikely and rather suggest the involvement of additional committed components.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Astrocytes / cytology*
  • Cell Cycle
  • Cell Differentiation
  • Cell Lineage
  • Cell Proliferation
  • Cell Size
  • Cerebellum / cytology*
  • Cerebellum / embryology
  • Clone Cells
  • Computer Simulation
  • Female
  • Humans
  • Mice, Inbred C57BL
  • Models, Biological
  • White Matter / cytology

Grant support

Local funds of the University of Turin (grant number). Received by AB. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Ministero dell’Istruzione, dell’Università e della Ricerca – MIUR project "Dipartimenti di Eccellenza 2018 – 2022" (grant number ex L. 232/2016). Received by the Department of Neuroscience "Rita Levi Montalcini". The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Ministry of Economy and Competitiveness of Spain (grant number BFU2016-75207-R). Received by LLM and supporting MFO. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Network of European Neuroscience Schools Fellowship (grant number). Received by VC. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. SystemsX.ch transition postdoc fellowship (grant number). Received by MB. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.