Human organomics: a fresh approach to understanding human development using single-cell transcriptomics

Abstract

Innovative methods designed to recapitulate human organogenesis from pluripotent stem cells provide a means to explore human developmental biology. New technologies to sequence and analyze single-cell transcriptomes can deconstruct these 'organoids' into constituent parts, and reconstruct lineage trajectories during cell differentiation. In this Spotlight article we summarize the different approaches to performing single-cell transcriptomics on organoids, and discuss the opportunities and challenges of applying these techniques to generate organ-level, mechanistic models of human development and disease. Together, these technologies will move past characterization to the prediction of human developmental and disease-related phenomena.

Single-Cell Transcriptomics of Traced Epidermal and Hair Follicle Stem Cells Reveals Rapid Adaptations during Wound Healing

“…Recent advances in single-cell transcriptomics have made it possible to monitor cell-type-specific transcriptional processes, such as lineage progression during organ development or tissue homeostasis, within complex tissues at unprecedented resolution (Camp and Treutlein, 2017;Sandberg, 2014;Tanay and Regev, 2017). Here, we combined lineage tracing of Lgr5-or Lgr6-expressing SCs with single-cell transcriptome analyses of thousands of individual cells to capture the molecular adaptation of SC progeny from different niches during wound healing.…”

ATOH1/RFX1/RFX3 transcription factors facilitate the differentiation and characterisation of inner ear hair cell-like cells from patient-specific induced pluripotent stem cells harbouring A8344G mutation of mitochondrial DNA

“…Interestingly, the generation of tissue-specific organoids has been suggested to be important in the modelling of cell–cell interactions in the three-dimensional level during organ development 47 . Koehler et al 48 reported the generation of inner ear organoids from human ESCs and iPSCs and demonstrated that inner ear organoids can have sensory epithelial cells due to the expression of HC markers, such as ESPN and MYO7A.…”

Genetic Modification of Brain Organoids

“…These methods make use of a differential expression of fluorophore combinations or other cell barcoding techniques. As to brain organoids, these approaches of cell lineage tracing could constitute a vital experimental avenue to confirm and complement in silico lineage analyses derived from single-cell sequencing (Camp and Treutlein, 2017;Camp et al, 2018). A significant advance in this context would be the transcriptomic analysis of defined cell subpopulations with an identified location within brain organoids, labeled via lineage-specific expression of fluorescent proteins.…”