Spatiotemporal gene expression trajectories reveal developmental hierarchies of the human cortex

Spatiotemporal gene expression trajectories reveal developmental hierarchies of the human cortex. Nowakowski, T. J, Bhaduri, A., Pollen, A. A, Alvarado, B., Mostajo-Radji, M. A, Di Lullo, E., Haeussler, M., Sandoval-Espinosa, C., Liu, S. J., Velmeshev, D., Ounadjela, J. R., Shuga, J., Wang, X., Lim, D. A, West, J. A, Leyrat, A. A, Kent, W J., & Kriegstein, A. R Science, 358(6368):1318–1323, December, 2017.
abstract bibtex

Systematic analyses of spatiotemporal gene expression trajectories during organogenesis have been challenging because diverse cell types at different stages of maturation and differentiation coexist in the emerging tissues. We identified discrete cell types as well as temporally and spatially restricted trajectories of radial glia maturation and neurogenesis in developing human telencephalon. These lineage-specific trajectories reveal the expression of neurogenic transcription factors in early radial glia and enriched activation of mammalian target of rapamycin signaling in outer radial glia. Across cortical areas, modest transcriptional differences among radial glia cascade into robust typological distinctions among maturing neurons. Together, our results support a mixed model of topographical, typological, and temporal hierarchies governing cell-type diversity in the developing human telencephalon, including distinct excitatory lineages emerging in rostral and caudal cerebral cortex.

@ARTICLE{Nowakowski2017-et,
  title    = "Spatiotemporal gene expression trajectories reveal developmental
              hierarchies of the human cortex",
  author   = "Nowakowski, Tomasz J and Bhaduri, Aparna and Pollen, Alex A and
              Alvarado, Beatriz and Mostajo-Radji, Mohammed A and Di Lullo,
              Elizabeth and Haeussler, Maximilian and Sandoval-Espinosa, Carmen
              and Liu, Siyuan John and Velmeshev, Dmitry and Ounadjela, Johain
              Ryad and Shuga, Joe and Wang, Xiaohui and Lim, Daniel A and West,
              Jay A and Leyrat, Anne A and Kent, W James and Kriegstein, Arnold
              R",
  abstract = "Systematic analyses of spatiotemporal gene expression
              trajectories during organogenesis have been challenging because
              diverse cell types at different stages of maturation and
              differentiation coexist in the emerging tissues. We identified
              discrete cell types as well as temporally and spatially
              restricted trajectories of radial glia maturation and
              neurogenesis in developing human telencephalon. These
              lineage-specific trajectories reveal the expression of neurogenic
              transcription factors in early radial glia and enriched
              activation of mammalian target of rapamycin signaling in outer
              radial glia. Across cortical areas, modest transcriptional
              differences among radial glia cascade into robust typological
              distinctions among maturing neurons. Together, our results
              support a mixed model of topographical, typological, and temporal
              hierarchies governing cell-type diversity in the developing human
              telencephalon, including distinct excitatory lineages emerging in
              rostral and caudal cerebral cortex.",
  journal  = "Science",
  volume   =  358,
  number   =  6368,
  pages    = "1318--1323",
  month    =  dec,
  year     =  2017,
  language = "en"
}

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