Molecular signature of primate astrocytes reveals pathways and regulatory changes contributing to human brain evolution
Astrocytes contribute to the development and regulation of the higher-level functions of the brain, the critical targets of evolution. However, how astrocytes evolve in primates is unsettled. Here, we obtain human, chimpanzee, and macaque induced pluripotent stem-cell-derived astrocytes (iAstrocytes). Human iAstrocytes are bigger and more complex than the non-human primate iAstrocytes. We identify new loci contributing to the increased human astrocyte. We show that genes and pathways implicated in long-range intercellular signaling are activated in the human iAstrocytes and partake in controlling iAstrocyte complexity. Genes downregulated in human iAstrocytes frequently relate to neurological disorders and were decreased in adult brain samples. Through regulome analysis and machine learning, we uncover that functional activation of enhancers coincides with a previously unappreciated, pervasive gain of "stripe" transcription factor binding sites. Altogether, we reveal the transcriptomic signature of primate astrocyte evolution and a mechanism driving the acquisition of the regulatory potential of enhancers.
Authors
- Eryk Duński (ORCID: https://orcid.org/0000-0003-1940-936X)
- Aleksandra Piotrowska (ORCID: https://orcid.org/0000-0003-4093-7386)
- Katarzyna Ciuba (ORCID: https://orcid.org/0000-0001-6629-218X)
- Debasish Chaudhury (ORCID: https://orcid.org/0000-0002-9089-732X)
- Tomasz P. Wypych (ORCID: https://orcid.org/0000-0003-0558-7923)
- Rüdiger Behr (ORCID: https://orcid.org/0000-0001-8816-6619)
- Edyta Bulanda (ORCID: https://orcid.org/0000-0002-8916-1569)
- Jakub Włodarczyk (ORCID: https://orcid.org/0000-0001-8343-2340)
- Karolina Soroczyńska (ORCID: https://orcid.org/0000-0002-4281-1528)
- Izabela Figiel (ORCID: https://orcid.org/0000-0001-5028-0168)
- Aleksandra Pękowska (ORCID: https://orcid.org/0000-0002-0425-4388)
- Misbah Abbas (ORCID: https://orcid.org/0000-0002-0100-7488)
- Marcin Niedbała (ORCID: https://orcid.org/0000-0002-6617-0155)
- Bondita Dehingia (ORCID: https://orcid.org/0000-0003-3688-4680)
- Wojciech Kaspera (ORCID: https://orcid.org/0000-0002-7139-3409)
- Malgorzata Czystowska (ORCID: https://orcid.org/0000-0001-9169-6194)
- Bartek Wilczyński (ORCID: https://orcid.org/0000-0002-8134-0589)
- Alexei Verkhratsky (ORCID: https://orcid.org/0000-0003-2592-9898)
- Sylwia Gawlik-Zawiślak (ORCID: https://orcid.org/0000-0003-4973-6433)
- Sylwia Pietrzak
Institutions
- Medical University of Silesia (PL)
- Instytut Biologii Doświadczalnej im. Marcelego Nenckiego (PL)
- Medical University of Warsaw (PL)
- Institute of Psychiatry and Neurology (PL)
- Institute of Occupational Medicine and Environmental Health (PL)
- University of Warsaw (PL)
- Polish Academy of Sciences (PL)
Publication Details
- Journal
- Cell stem cell
- Published
- 2025-02-04
- DOI
- https://doi.org/10.1016/j.stem.2024.12.011
- Citations
- 9
- Primary Topic
- RNA Research and Splicing
- Type
- article
- Field-Weighted Citation Impact
- 7.25
Funders
- European Molecular Biology Organization
- Narodowe Centrum Nauki