Single-cell transcriptome profiling of the human developing spinal cord reveals a conserved genetic programme with human-specific features

Rayón, Teresa; Maizels, Rory J; Barrington, Christopher; Briscoe, James

doi:10.1242/dev.199711

Cited by 80 publications

(89 citation statements)

References 53 publications

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“…3 figure supplement 1 and T. Rayon pers comm.). This suggests that these interneurons are just beginning to be generated at CS13 at thoracic/ brachial levels and is consistent with detection of LHX2 expressing neurons in CS14 spinal cord (Marklund et al 2014) and see (Rayon et al 2020, Rayon et al 2021. In contrast, LHX2 positive cells were first detected in D8 rosettes and both LHX2 and ISLET1 positive cells were found in all D10 neural rosettes (Figs.…”

Section: Sequential Differentiation Of Human Dorsal Spinal Cord Proge...supporting

confidence: 83%

Human spinal cord in vitro differentiation pace is initially maintained in heterologous embryonic environments

Dady

Davidson

Halley

et al. 2022

eLife

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Species-specific differentiation pace in-vitro indicates that some aspects of neural differentiation are governed by cell intrinsic properties. Here we describe a novel in-vitro human neural-rosette assay that recapitulates dorsal spinal cord differentiation but proceeds more rapidly than in the human embryo, suggesting that it lacks endogenous signalling dynamics. To test whether in-vitro conditions represent an intrinsic differentiation pace, human iPSC-derived neural rosettes were challenged by grafting into the faster differentiating chicken embryonic neural tube iso-chronically, or hetero-chronically into older embryos. In both contexts in-vitro differentiation pace was initially unchanged, while long-term analysis revealed iso-chronic slowed and hetero-chronic conditions promoted human neural differentiation. Moreover hetero-chronic conditions did not alter the human neural differentiation programme, which progressed to neurogenesis, while the host embryo advanced into gliogenesis. This study demonstrates that intrinsic properties limit human differentiation pace, and that timely extrinsic signals are required for progression through an intrinsic human neural differentiation programme.

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Section: Sequential Differentiation Of Human Dorsal Spinal Cord Proge...supporting

confidence: 83%

Human spinal cord in vitro differentiation pace is initially maintained in heterologous embryonic environments

Dady

Davidson

Halley

et al. 2022

eLife

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“…This revealed sets of transcription factors (TFs), expressed at characteristic time points during the neurogenic period of spinal cord development, which further partition all major neuronal subtypes ( Fig 1A ). In all domains, the earliest neurons express Onecut family TFs, intermediate neurons express Pou2f2 and Zfhx2-4, while at late stages, subsets of neurons start to express Nfia/b/x, Neurod2/6, and Tcf4 [ 33 – 35 ]. This suggested the existence of a previously unappreciated temporal dimension to neuronal subtype generation in the spinal cord.…”

Section: Introductionmentioning

confidence: 99%

A shared transcriptional code orchestrates temporal patterning of the central nervous system

et al. 2021

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The molecular mechanisms that produce the full array of neuronal subtypes in the vertebrate nervous system are incompletely understood. Here, we provide evidence of a global temporal patterning program comprising sets of transcription factors that stratifies neurons based on the developmental time at which they are generated. This transcriptional code acts throughout the central nervous system, in parallel to spatial patterning, thereby increasing the diversity of neurons generated along the neuraxis. We further demonstrate that this temporal program operates in stem cell−derived neurons and is under the control of the TGFβ signaling pathway. Targeted perturbation of components of the temporal program, Nfia and Nfib, reveals their functional requirement for the generation of late-born neuronal subtypes. Together, our results provide evidence for the existence of a previously unappreciated global temporal transcriptional program of neuronal subtype identity and suggest that the integration of spatial and temporal patterning mechanisms diversifies and organizes neuronal subtypes in the vertebrate nervous system.

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“…Finally, to determine if MMC MN diversity is conserved in human, we investigated the distributions of SATB2, NR2F2 and BCL11B in human embryo spinal cord sections at Carnegie stage 18, from Gestational Week (GW) 6.3 (equivalent to mouse E13.5 embryos when most MN columnar identities have been established) 79, 80 ( Fig. 7f and Extended Data Fig.…”

Section: Resultsmentioning

confidence: 99%

Single-cell transcriptomic analysis unveils spinal motor neuron subtype diversity underpinning the water-to-land transition in vertebrates

Liau

Jin

Chen

et al. 2021

Preprint

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Spinal motor neurons (MNs) integrate sensory stimuli and brain commands to generate motor movements in vertebrates. Distinct MN populations and their diversity has long been hypothesized to co-evolve with motor circuit to provide the neural basis from undulatory to ambulatory locomotion during aquatic-to-terrestrial transition of vertebrates. However, how these subtypes are evolved remains largely enigmatic. Using single-cell transcriptomics, we investigate heterogeneity in mouse MNs and discover novel segment-specific subtypes. Among limb-innervating MNs, we reveal a diverse neuropeptide code for delineating putative motor pool identities. We further uncovered that axial MNs are subdivided by three conserved and molecularly distinct subpopulations, defined by Satb2, Nr2f2 or Bcl11b expression. Although axial MNs are conserved from cephalochordates to humans, subtype diversity becomes prominent in land animals and appears to continue evolving in humans. Overall, our study provides a unified classification system for spinal MNs and paves the way towards deciphering how neuronal subtypes are evolved.

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Single-cell transcriptome profiling of the human developing spinal cord reveals a conserved genetic programme with human-specific features

Cited by 80 publications

References 53 publications

Human spinal cord in vitro differentiation pace is initially maintained in heterologous embryonic environments

Human spinal cord in vitro differentiation pace is initially maintained in heterologous embryonic environments

A shared transcriptional code orchestrates temporal patterning of the central nervous system

Single-cell transcriptomic analysis unveils spinal motor neuron subtype diversity underpinning the water-to-land transition in vertebrates

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