Deciphering how the human striatum develops is necessary for understanding the diseases that affect this region. To decode the transcriptional modules that regulate this structure during development, we compiled a catalog of 1116 long intergenic noncoding RNAs (lincRNAs) identified de novo and then profiled 96,789 single cells from the early human fetal striatum. We found that D1 and D2 medium spiny neurons (D1- A nd D2-MSNs) arise from a common progenitor and that lineage commitment is established during the postmitotic transition, across a pre-MSN phase that exhibits a continuous spectrum of fate determinants. We then uncovered cell type-specific gene regulatory networks that we validated through in silico perturbation. Finally, we identified human-specific lincRNAs that contribute to the phylogenetic divergence of this structure in humans. This work delineates the cellular hierarchies governing MSN lineage commitment.

The coding and long noncoding single-cell atlas of the developing human fetal striatum / V.D. Bocchi, P. Conforti, E. Vezzoli, D. Besusso, C. Cappadona, T. Lischetti, M. Galimberti, V. Ranzani, R.J.P. Bonnal, M.D. De Simone, G. Rossetti, X. He, K. Kamimoto, I. Espuny-Camacho, A. Faedo, F. Gervasoni, R. Vuono, S.A. Morris, J. Chen, D. Felsenfeld, G. Pavesi, R.A. Barker, M. Pagani, E. Cattaneo. - In: SCIENCE. - ISSN 0036-8075. - 372:6542(2021), pp. abf5759.1-abf5759.11. [10.1126/science.abf5759]

The coding and long noncoding single-cell atlas of the developing human fetal striatum

P. Conforti;E. Vezzoli;D. Besusso;C. Cappadona;T. Lischetti;M. Galimberti;V. Ranzani;X. He;A. Faedo;F. Gervasoni;G. Pavesi;M. Pagani;E. Cattaneo
Ultimo
2021

Abstract

Deciphering how the human striatum develops is necessary for understanding the diseases that affect this region. To decode the transcriptional modules that regulate this structure during development, we compiled a catalog of 1116 long intergenic noncoding RNAs (lincRNAs) identified de novo and then profiled 96,789 single cells from the early human fetal striatum. We found that D1 and D2 medium spiny neurons (D1- A nd D2-MSNs) arise from a common progenitor and that lineage commitment is established during the postmitotic transition, across a pre-MSN phase that exhibits a continuous spectrum of fate determinants. We then uncovered cell type-specific gene regulatory networks that we validated through in silico perturbation. Finally, we identified human-specific lincRNAs that contribute to the phylogenetic divergence of this structure in humans. This work delineates the cellular hierarchies governing MSN lineage commitment.
Corpus Striatum; Fetus; GABAergic Neurons; Humans; Neurogenesis; RNA, Long Noncoding; RNA-Seq; Transcription Factors; Transcription, Genetic; Atlases as Topic; Single-Cell Analysis
Settore BIO/14 - Farmacologia
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/877959
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