A single-cell transcriptome atlas profiles early organogenesis in human embryos

Abstract

The early window of human embryogenesis is largely a black box for developmental biologists. Here we probed the cellular diversity of 4-to 6-week human embryos when essentially all organs are just laid out. Based on over 180,000 single-cell transcriptomes, we generated a comprehensive atlas of 313 cell types in 18 developmental systems, which were annotated with a collection of ontology and markers from 157 publications. Together with spatial transcriptome on embryonic sections, we characterized the molecule and spatial architecture of previously unappreciated cell types. Combined with data from other vertebrates, the rich information shed light on spatial patterning of axes, systemic temporal regulation of developmental progression and potential human-specific regulation. Our study provides a compendium of early progenitor cells of human organs, which can serve as the root of lineage analysis in

TLNRD1 is a CCM complex component and regulates endothelial barrier integrity

“…Similarly, TL-NRD1 is also expressed in the vasculature in human embryos (Fig. S2C, (Xu et al, 2023)). Importantly, reanalysis of publicly available datasets revealed that TLNRD1 expression is up-regulated in CCM lesions from patients (Fig.…”

Spatiotemporal transcriptome atlas of human embryos after gastrulation

“…During this period, most named parts of the body become identifiable, and many congenital birth defects and developmental disorders may also originate from this susceptible window of development. In recent years, powerful approaches have emerged which enabled the charting of dynamic changes during human development at singlecell resolution 11,12,17,[67][68][69][70][71][72] , and recent spatial transcriptome data illustrated spatial transcriptional characteristics and complex architectures of certain developing organs 14,15,18,19 . Xu et al also provided a spatially mapped view of a PCW5 embryo 12 .…”

“…In recent years, powerful approaches have emerged which enabled the charting of dynamic changes during human development at singlecell resolution 11,12,17,[67][68][69][70][71][72] , and recent spatial transcriptome data illustrated spatial transcriptional characteristics and complex architectures of certain developing organs 14,15,18,19 . Xu et al also provided a spatially mapped view of a PCW5 embryo 12 . In this study, our characterization provides a panoramic transcriptome atlas of in vivo human embryogenesis after gastrulation in both spatial and temporal resolution.…”

“…Previously, great efforts were made to establish the gene-expression landscapes during early human embryogenesis. For instance, recent advancements in single-cell RNA sequencing (scRNA-seq) technologies have allowed a comprehensive analysis of human cellular heterogeneity in 15 fetal organs consisting of more than 4 million cells collected from 72 to 129 days of post-conception age 11 , and, data from Xu et al also provides a single-cell transcriptome atlas of early embryo 12 . However, data crossing embryonic stages post-gastrulation remains unavailable.…”

“…It also underlines the significance of studying human samples, as model organisms cannot fully reflect the unique aspects of human development. Though two sagittal sections of a PCW5 human embryo were spatially mapped 12 , there still lacks developmental dynamics of whole-embryo spatial transcriptome atlas due to excessive embryo size exceeding the limits of the most current spatial transcriptome technology. Hence, the molecular mechanisms of the cellular diversity and intricately orchestrated organogenesis in human embryo still requires better illustrations.…”