Function and mechanisms specifying the heterogeneity of forebrain astrocytes

• Applicant: Professorin Dr. Magdalena Götz
• Subject Area: Molecular Biology and Physiology of Neurons and Glial Cells ; Developmental Neurobiology
• Term: from 2014 to 2020
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 254847613

• Final Report Year: 2021

Final Report Abstract

One of the most interesting outcome of the single cell sequencing of astrocytes in the forebrain is the identification of astrocyte subsets with more wide-spread mapping using the Visium site, while others appear more region-specific. This explains why astrocytes share aspects across all regions, such as glutamate transport, etc., while others carry more region-specific information. The other main outcome is the novel concept of adult astrocytogenesis, albeit at low level, in a region-specific manner. It will be now important to understand how this is regulated and what the function of the adult generated astrocytes. In addition, we could identify the key function of juxtavascular astrocytes and identify their differences even in the intact brain and identify their potential to self-renew and functional differences to the bonafide neural stem cells.

Publications

• (2015) Astrocyte reactivity after brain injury - The role of galectins 1 and 3. Glia 63, 2340-2361
  Sirko S., Irmler M., Gascón S., Bek S., Schneider S., Dimou L., Obermann J., De Souza Paiva D., Poirier F., Beckers J., Hauck S.M., Barde Y.A. and Götz M.
  (See online at https://doi.org/10.1002/glia.22898)
• (2016) Astrocytic insulin signaling couples brain glucose uptake with nutrient availability. Cell 166, 867-80
  Garcia-Caceres C., Carmelo Q., Varela L, Gao Y., Gruber T., Legutko B., Jastroch M., Johansson P., Ninkovic J., Yi C-X., Le Thuc O., Szigeti-Buck K., Cai W., Meyer C.W., Pfluger P.T., Fernandez A.M., Luquet S., Woods S.C., Torres-Alemán I., Kahn C.R., Götz M., Horvath T.L. and Tschöp M.H.
  (See online at https://doi.org/10.1016/j.cell.2016.07.028)
• (2016) Loss of Uhrf1 in neural stem cells leads to activation of retroviral elements and delayed neurodegeneration. Genes & Development 30, 2199-2212
  Ramesh V., Bayam E., Cernilogar F.M., Bonapace I.M, Schulze M., Riemenschneider M.J., Schotta G. and Götz M.
  (See online at https://doi.org/10.1101/gad.284992.116)
• (2016) Transplanted embryonic neurons integrate into adult neocortical circuits. Nature 539, 248-253
  Falkner S., Grade S., Dimou L., Conzelmann K.-K., Bonhoeffer T., Götz M. and Hübener M.
  (See online at https://doi.org/10.1038/nature20113)
• (2017) Changes in the Proliferative Program Limit Astrocyte Homeostasis in the Aged Post-Traumatic Murine. Cerebral Cortex 27, 4213-4228
  Heimann G., Canhos L.L., Frik J., Jäger G., Lepko T., Ninkovic J., Götz M. and Sirko S.
  (See online at https://doi.org/10.1093/cercor/bhx112)
• (2017) Time-Specific Effects of Spindle Positioning on Embryonic Progenitor Pool Composition and Adult Neural Stem Cell Seeding. Neuron 93, 777-791
  Falk S., Bugeon S., Ninkovic J., Pilz G.-A., Postiglione M.-P., Cremer H., Knoblich J.A. and Götz M.
  (See online at https://doi.org/10.1016/j.neuron.2017.02.009)
• (2018) Cell tracking in vitro reveals that the extracellular matrix glycoprotein Tenascin-C modulates cell cycle length and differentiation in neural stem/progenitor cells of the developing mouse spinal cord. Biol Open 7(7)
  May M., Denecke B., Schroeder T., Götz M. and Faissner A.
  (See online at https://doi.org/10.1242/bio.027730)
• (2018) Cross-talk between monocyte invasion and astrocyte proliferation regulates scarring in brain injury. EMBO Reports 19, e45294
  Frik J., Merl-Pham J., Plesnila N., Mattugini M., Kjell J., Kraska J., Gómez R.M., Hauck S.M., Sirko S. and Götz M.
  (See online at https://doi.org/10.15252/embr.201745294)
• (2018) Epithelial sodium channel regulates adult neural stem cell proliferation in a flow-dependent manner. Cell Stem Cell 22, 865-878. Highlighted by Kaneko and Sawamoto, Cell Stem Cell 22, 783-784
  Petrik D., Myoga M.H., Grade S., Gerkau N.J., Pusch M., Rose C.R., Grothe B. and Götz M.
  (See online at https://doi.org/10.1016/j.stem.2018.04.016)
• (2018) Influence of white matter injury on gray matter reactive gliosis upon stab wound in the adult murine cerebral cortex. Glia 66, 1644-1662
  Mattugini N., Merl-Pham J., Petrozziello E., Schindler L., Bernhagen J., Hauck S.M. and Götz M.
  (See online at https://doi.org/10.1002/glia.23329)
• (2018) New approaches to brain repair: from rescue to reprogramming. Nature 557, 329-334
  Barker R.A., Götz M. and Parmar M.
  (See online at https://doi.org/10.1038/s41586-018-0087-1)
• (2019) Choroid-plexusderived miR-204 regulates the number of quiescent neural stem cells in the adult brain. EMBO J. 38, e100481
  Lepko T., Pusch M., Müller T., Schulte D., Ehses J., Kiebler M., Hasler J., Huttner H.B., Vandenbroucke R.E., Vandendriessche C., Modic M., Martin-Villalba A., Zhao S., LLorens-Bobadilla E., Schneider A., Fischer A., Breunig C.T., Stricker S.H., Götz M. and Ninkovic J.
  (See online at https://doi.org/10.15252/embj.2018100481)
• (2020) Trnp1 organizes diverse nuclear membrane-less compartments in neural stem cells. The EMBO Journal 39, e103373
  Esgleas M., Falk S., Forné I., Thiry M., Najas S., Zhang S., Mas-Sanchez A., Geerlof A., Niessing D., Wang Z., Imhof A. and Götz M.
  (See online at https://doi.org/10.15252/embj.2019103373)
• (2020). CRISPR-mediated induction of neuron-enriched mitochondrial proteins boosts direct glia-toneuron conversion. Cell Stem Cell
  Russo G.L., Sonsalla G., Natarajan P., Breunig C.T., Bulli G., Merl-Pham J., Schmitt S., Giehrl-Schwab J., Giesert F., Jastroch M., Zischka H., Wurst W., Stricker S.H., Hauck S.M., Masserdotti G. and Götz M.
  (See online at https://doi.org/10.1016/j.stem.2020.10.015)
• (2021) Heterogeneity of astrocytes: electrophysiological properties of juxtavascular astrocytes before and after brain injury. Glia 69, 346-361
  Götz S., Bribrian A., Lopez-Mascaraque L., Götz M., Grothe B. and Kunz L.
  (See online at https://doi.org/10.1002/glia.23900)
• (2021) Repetitive injury and absence of monocytes promote astrocyte self-renewal and neurological recovery. Glia 69,165-181
  Lange Canhos L., Chen M., Falk S., Popper B., Straub T., Götz M. and Sirko S.
  (See online at https://doi.org/10.1002/glia.23893)