TY - JOUR
T1 - Cortical somatostatin long-range projection neurons and interneurons exhibit divergent developmental trajectories
AU - Fisher, Josephine
AU - Verhagen, Marieke
AU - Long, Zhen
AU - Moissidis, Monika
AU - Yan, Yiming
AU - He, Chenyi
AU - Wang, Jingyu
AU - Micoli, Elia
AU - Alastruey, Clara Milían
AU - Moors, Rani
AU - Marín, Oscar
AU - Mi, Da
AU - Lim, Lynette
N1 - Funding Information:
We thank E. Serafeimidou-Pouliou for general laboratory support, C. Zimmer for help with retroviral experiments, I. Andrew for managing mouse colonies, and the Flow Cytometry and Genomics Platforms at the Guy’s and St Thomas’ NHS Foundation Trust and King’s College London Biomedical Research Centre for technical support. We also thank the VIB Flow Core Leuven and VIB-CBD Single Cell & Microfluidics Units. We thank Genevia Technologies for their help with statistical analyses. We are also grateful to members of the Lim, Marín, Mi, and Rico laboratories for stimulating discussions and ideas and to Nicholas Luscombe for guidance and support on bioinformatic analyses. This work was supported by grants from the Wellcome Trust ( 215556/Z/19/Z ) to O.M., the Research Foundation – Flanders (FWO) Junior Research Project Fundamental Research ( G057121N ), the FWO-Odysseus Award ( G0E9121N ), and the VIB Technology Watch (Techwatch) grant (Spatial technologies) to L.L., and the Ministry of Science and Technology of China ( STI2030-Major Projects 2021ZD0202300 ) and the National Natural Science Foundation of China ( 32271024 ) to D.M. E.M. was the recipient of an FWO PhD fundamental fellowship ( 1192822N ).
Funding Information:
We thank E. Serafeimidou-Pouliou for general laboratory support, C. Zimmer for help with retroviral experiments, I. Andrew for managing mouse colonies, and the Flow Cytometry and Genomics Platforms at the Guy's and St Thomas’ NHS Foundation Trust and King's College London Biomedical Research Centre for technical support. We also thank the VIB Flow Core Leuven and VIB-CBD Single Cell & Microfluidics Units. We thank Genevia Technologies for their help with statistical analyses. We are also grateful to members of the Lim, Marín, Mi, and Rico laboratories for stimulating discussions and ideas and to Nicholas Luscombe for guidance and support on bioinformatic analyses. This work was supported by grants from the Wellcome Trust (215556/Z/19/Z) to O.M. the Research Foundation – Flanders (FWO) Junior Research Project Fundamental Research (G057121N), the FWO-Odysseus Award (G0E9121N), and the VIB Technology Watch (Techwatch) grant (Spatial technologies) to L.L. and the Ministry of Science and Technology of China (STI2030-Major Projects 2021ZD0202300) and the National Natural Science Foundation of China (32271024) to D.M. E.M. was the recipient of an FWO PhD fundamental fellowship (1192822N). Conceptualization, L.L. O.M. and D.M.; methodology, J.F. M.V. L.L. D.M. and O.M.; investigation, M.V. Z.L. M.M. R.M. E.M. C.M.A. L.L. and D.M.; data curation, J.F. C.H. Y.Y. - J.W. L.L. and D.M.; formal analysis, J.F. C.H. Y.Y. and J.W.; writing – original draft, D.M. O.M. and L.L.; writing – review & editing, M.V. J.F. M.M. Z.L. D.M. O.M. and L.L.; funding acquisition, L.L. O.M. and D.M.; resources, L.L. O.M. and D.M.; supervision, L.L. M.V. O.M. and D.M. The authors declare no competing interests. We support inclusive, diverse, and equitable conduct of research. One or more of the authors of this paper received support from a program designed to increase minority representation in their field of research.
Publisher Copyright:
© 2023 The Authors
PY - 2024/2/21
Y1 - 2024/2/21
N2 - The mammalian cerebral cortex contains an extraordinary diversity of cell types that emerge by implementing different developmental programs. Delineating when and how cellular diversification occurs is particularly challenging for cortical inhibitory neurons because they represent a small proportion of all cortical cells and have a protracted development. Here, we combine single-cell RNA sequencing and spatial transcriptomics to characterize the emergence of neuronal diversity among somatostatin-expressing (SST+) cells in mice. We found that SST+ inhibitory neurons segregate during embryonic stages into long-range projection (LRP) neurons and two types of interneurons, Martinotti cells and non-Martinotti cells, following distinct developmental trajectories. Two main subtypes of LRP neurons and several subtypes of interneurons are readily distinguishable in the embryo, although interneuron diversity is likely refined during early postnatal life. Our results suggest that the timing for cellular diversification is unique for different subtypes of SST+ neurons and particularly divergent for LRP neurons and interneurons.
AB - The mammalian cerebral cortex contains an extraordinary diversity of cell types that emerge by implementing different developmental programs. Delineating when and how cellular diversification occurs is particularly challenging for cortical inhibitory neurons because they represent a small proportion of all cortical cells and have a protracted development. Here, we combine single-cell RNA sequencing and spatial transcriptomics to characterize the emergence of neuronal diversity among somatostatin-expressing (SST+) cells in mice. We found that SST+ inhibitory neurons segregate during embryonic stages into long-range projection (LRP) neurons and two types of interneurons, Martinotti cells and non-Martinotti cells, following distinct developmental trajectories. Two main subtypes of LRP neurons and several subtypes of interneurons are readily distinguishable in the embryo, although interneuron diversity is likely refined during early postnatal life. Our results suggest that the timing for cellular diversification is unique for different subtypes of SST+ neurons and particularly divergent for LRP neurons and interneurons.
UR - http://www.scopus.com/inward/record.url?scp=85182355426&partnerID=8YFLogxK
U2 - 10.1016/j.neuron.2023.11.013
DO - 10.1016/j.neuron.2023.11.013
M3 - Article
SN - 0896-6273
VL - 112
SP - 558-573.e8
JO - Neuron
JF - Neuron
IS - 4
ER -