Human Developmental Cell Atlas: milestones achieved and the roadmap ahead

Abstract

The Human Developmental Cell Atlas (HDCA), as part of the Human Cell Atlas, aims to generate a comprehensive reference map of cells during development. This detailed study of development will be critical for understanding normal organogenesis, the impact of mutations, environmental factors and infectious agents on congenital and childhood disorders, and the molecular cellular basis of ageing, cancer and regenerative medicine. In this perspective, we outline the challenges of mapping and modelling human development using state of the art technologies to create a reference atlas across gestation for scientific and clinical benefit. We discuss the potential value of HDCA to enhance human pluripotent stem cell-derived organoid model systems and, in turn, the use of organoids and animal models to inform HDCA. Finally, we provide a roadmap towards a complete atlas of human development.

Generation and characterization of hair-bearing skin organoids from human pluripotent stem cells

“…Therefore, most skin studies have used murine models, resulting in a lack of mechanistic insight into the specification of cell types during human development. International consortium efforts to map developing cell lineages in organoids and human fetal tissue should shed light on these mechanisms 40,41 . Single-cell sequencing approaches, such as RNA sequencing and assay for transposase-accessible chromatin (ATAC) using sequencing, can be performed on skin organoids.…”

“…We provide a method for dissociating skin organoids to facilitate such studies. The skin organoid single-cell RNA sequencing (scRNA-seq) data can be compared with skin atlases available through the Human Cell Atlas data portal 41,42 . Based on our scRNA-seq and immunostaining data, the end-stage skin organoids (~150 d of culture) represent the human skin tissues at the second-trimester stage of the developing fetus 25 .…”

Mapping Cell Atlases at the Single‐Cell Level

“…The aim of the HDCA is to create a comprehensive single-cell reference map during normal organogenesis and early development stages to lay the foundation for aging, cancer, and regenerative medicine. [64] The organoid cell atlas presents the first framework for drug development and therapies for cancer, rare genetic diseases, and multifactorial disorders. [65] During the years 2017-2019, research teams from Qiao and Tang's laboratory reported a series of multiomics studies to map the development of human germline cells and embryo implantation.…”

Skin organoids: A new human model for developmental and translational research

“…For example, Botting et al recently generated a reference map of foetal liver haematopoiesis and establishment of immune cells in the skin and lung 56,57 . A component of the HCA’s ongoing work on a Developmental Cell Atlas will use stem cell‐derived organoids as a complementary cell source for difficult to obtain human foetal tissue 58,59 . This work will provide a tremendous resource for future investigations into the stem/progenitor cells that arise during human skin formation.…”