The Human Developmental Cell Atlas (HDCA, often also HuDeCA after the French INSERM program) is the developmental-biology pillar of the Human Cell Atlas (HCA): an international research consortium that maps the cells of human embryonic and fetal development from gastrulation (CS 7) to the end of the fetal period at single-cell resolution.
The HuDeCA atlases supplement the classical, morphologically defined Carnegie convention with a cellular layer: which cell types exist at which stage, along which lineage trajectories do they diverge, at which spatial positions do they appear?
Consortial Structure
Three levels, nested within one another:
- HuDeCA (France, INSERM) — French research program within the HDCA network: biobank of embryonic/fetal organs, 3D imaging combined with scRNA-seq of eight first-trimester organs.
- Human Cell Atlas (HCA) — International consortium (founded 2016, Aviv Regev / Sarah Teichmann). Goal: complete mapping of all human cell types. Umbrella organization; HDCA/HuDeCA are the developmental subnetworks.
- Human Developmental Cell Atlas (HDCA) — Developmental-biology subnetwork of the HCA. Maps cells from gastrulation (CS 7) to the end of the fetal period. Roadmap: Haniffa & Teichmann et al. (Nature 597:196-205, 2021).
Further subnetworks are the Swedish HCA, the EU programs HUGODECA and Braintime, as well as the NIH initiatives dGTEx and BRAIN/BICCN.
Methods
- Single-cell transcriptomics (scRNA-seq) — gene expression of individual cells (10x Genomics, Smart-seq2, Drop-seq).
- Spatial transcriptomics — gene expression with position in the tissue (Visium, Stereo-seq, MERFISH, seqFISH).
- scATAC-seq — chromatin accessibility at the single-cell level (Domcke 2020).
- 3D imaging combined with scRNA-seq (HuDeCA-FR).
- Pseudotime inference and lineage tracing reconstruct differentiation trajectories from snapshot data.
Important Atlases and Publications
| Publication | Content |
|---|---|
| Braun et al. 2023 (first-trimester brain atlas) | Braun E., Danan-Leon M., Hochgerner H., …, Linnarsson S. (2023): Comprehensive cell atlas of the first-trimester developing human brain. Science 382(6667):eadf1226. DOI 10.1126/science.adf1226. PMID 37824650. PCW 5–14, 12 classes, ~600 cell states. |
| Cao et al. 2020 (fetal atlas) | Cao J., O’Day D. R., Pliner H. A., …, Shendure J. (2020): A human cell atlas of fetal gene expression. Science 370(6518):eaba7721. DOI 10.1126/science.aba7721. PMID 33184181. ~4 million cells, 15 organs, 77 main types / 657 subtypes. |
| Domcke et al. 2020 (fetal chromatin) | Domcke S., Hill A. J., Daza R. M., …, Shendure J. (2020): A human cell atlas of fetal chromatin accessibility. Science 370(6518):eaba7612. DOI 10.1126/science.aba7612. |
| Haniffa & Teichmann et al. 2021 (HuDeCA roadmap) | Haniffa M., Teichmann S. A. et al. (2021): A roadmap for the Human Developmental Cell Atlas. Nature 597(7875):196–205. DOI 10.1038/s41586-021-03620-1. PMID 34497388. |
| Popescu et al. 2019 (fetal liver) | Popescu D.-M., Botting R. A., Stephenson E., …, Haniffa M. (2019): Decoding human fetal liver haematopoiesis. Nature 574(7778):365–371. DOI 10.1038/s41586-019-1652-y. |
| Rood/Regev et al. 2025 (HCA foundation model) | Rood J. E., Wynne S., Robson L., Hupalowska A., Randell J., Teichmann S. A., Regev A. (2025): The Human Cell Atlas from a cell census to a unified foundation model. Nature 637(8047):1065-1071. DOI 10.1038/s41586-024-08338-4. PMID 39566552. |
| Suo et al. 2022 (fetal immune system) | Suo C., Dann E., Goh I., Jardine L., Kleshchevnikov V., Park J.-E., Polanski K., Haniffa M., Teichmann S. A. et al. (2022): Mapping the developing human immune system across organs. Science 376(6597):eabo0510. DOI 10.1126/science.abo0510. PMID 35549310. |
| Tyser/Srinivas et al. 2021 (CS 7 gastrulation) | Tyser R. C. V., Mahammadov E., Nakanoh S., Vallier L., Scialdone A., Srinivas S. (2021): Single-cell transcriptomic characterization of a gastrulating human embryo. Nature 600(7888):285–289. DOI 10.1038/s41586-021-04158-y. PMID 34789876. |
| Zeng et al. 2023 (gastrulation + brain, spatial) | Zeng B., Liu Z., Lu Y. et al. (2023): The single-cell and spatial transcriptional landscape of human gastrulation and early brain development. Cell Stem Cell 30(6):851–866. DOI 10.1016/j.stem.2023.04.016. PMID 37192616. |
Cell Types Along the Carnegie Stages
The following table shows 14 cell types canonicalized in HuDeCA atlases, with the Carnegie stage at which they first become observable:
| Cell type | Observable from | Description |
|---|---|---|
| Epiblast | CS 3, CS 5 | Pluripotent cell type of the inner cell mass (CS 3) and the bilaminar germ disc (CS 5). Source of all three germ layers. Naive vs. primed pluripotency is distinguished here. |
| Erythro-myeloid progenitor (EMP) | CS 10, CS 11 | Multipotent progenitor of the second haematopoietic wave; gives rise to erythrocytes, megakaryocytes, and myeloid lineages including microglial precursors. Suo et al. 2022. |
| Glioblast | — | Differentiating glial precursor from radial glia. Branching into astrocyte and oligodendrocyte lineages. |
| Hemogenic endothelium | CS 10, CS 11 | Specialized endothelium (AGM region, yolk sac, placenta) from which haematopoietic stem cells arise via endothelial-to-haematopoietic transition. Origin of definitive haematopoiesis. |
| Hypoblast | CS 3, CS 5 | Cell population of the early bilaminar germ disc, ventral to the epiblast. Despite its non-embryonic lineage affiliation, it provides signaling cues for axis formation. |
| Neuroepithelial cell | CS 11, CS 8 | Pseudostratified cells of the neural plate and the early neural tube (CS 8–11). Origin of all neural lineages. |
| Paraxial mesoderm | CS 7, CS 9 | Mesoderm on both sides of the axis, segmenting into somites (CS 9 onward); source of skeletal musculature, the axial skeleton, and the dermis. |
| Pre-OPC (pre-oligodendrocyte precursor) | — | Early step of oligodendrocytic specification. Delineated in the first-trimester brain atlas (Braun 2023). |
| Primitive macrophage | CS 7, CS 8 | First macrophage population in the embryo, yolk-sac-derived (primitive haematopoiesis from CS 7 onward). Precursor of microglia and tissue-resident macrophages. |
| Primitive streak cell | CS 6, CS 7 | Cell population of the primitive streak (CS 6–7). Tyser/Srinivas (Nature 2021) characterized its transcriptomic subgroups for the first time in a CS 7 embryo. |
| Primordial germ cell (PGC) | CS 7, CS 8 | Precursor of the gametes. Specification in the posterior epiblast, migration via the allantois and hindgut to the genital ridge. Molecularly characterized in the CS 7 atlas (Tyser/Srinivas 2021). Relevant for arguments concerning germline continuity. |
| Radial glia | CS 12 | Central stem cell population of the developing CNS (from CS 12 onward). Gives rise to neurons and glia. Braun/Linnarsson 2023 distinguish multiple region-specific subtypes. |
| Immature cardiomyocyte | CS 10 | Early cardiac muscle cell type from CS 10 onward (first heartbeat); matures further over the course of the fetal phase. |
Important: A cell type is a biological category of cells, not a bearer of rational nature — and thus not a person. Personhood belongs to the integral organism, not to a single cell population. The ontology explicitly records this distinction of levels.
Lineage Trajectories
Three prominent HuDeCA findings concern the development of the blood and immune system in staggered haematopoietic waves:
- Definitive haematopoiesis — third haematopoietic wave: HSCs arise from the hemogenic endothelium of the AGM (aorta-gonad-mesonephros) region and the placenta, colonize the fetal liver as the main site of blood formation in the 1st–2nd trimester, and finally the bone marrow.
- EMP wave (erythro-myeloid progenitors) — second haematopoietic wave from CS 10–11 onward. Origin in yolk-sac hemogenesis; produces myeloid lineages (erythrocytes, megakaryocytes, early macrophages including microglial precursors).
- Primitive haematopoiesis — first wave of blood formation in the yolk sac from CS 7 onward; produces primitive erythrocytes and primitive macrophages. Precedes definitive haematopoiesis.
A fourth trajectory concerns the neural lineage: neuroepithelial cell → radial glia → glioblast → pre-OPC (Braun et al., Science 2023).
Personal-Ontological Assessment
The HuDeCA findings are empirical observations, not personal-ontological statements. Three effects on the ongoing debates:
-
Empirical support for the substance-ontological position. HuDeCA shows that cell-fate decisions are gradual, multi-peaked, and probabilistic — not point events. This sits well with the substance-ontological thesis that personhood depends on the integral organism from CS 1 onward, not on a later threshold moment.
-
Sharpening of the individuation debate. Tyser/Srinivas (Nature 2021) molecularizes the CS 7 embryo for the first time at the single-cell level. The Smith/Brogaard thesis of an individuation point at day 14–17 (primitive streak) can no longer be represented empirically as a leap — it becomes visible as the endpoint of a trajectory, which relieves the Damschen/Schönecker position (fertilization as the beginning).
-
Sharpening of the SCBEM debate. HuDeCA provides the transcriptomic comparison grid against which stem-cell-based embryo models (blastoids, gastruloids, post-implantation models) must be measured. If a model recapitulates the full single-cell signature of a post-gastrulation embryo, the question of its moral status can no longer be defined away morphologically.
HuDeCA does not solve the personal-ontological question — it dissociates it from individual cell milestones and shifts the burden of argument onto the integral organism.
Sources
Further sources — all checked for existence and correctness:
- Haniffa, M.; Teichmann, S. A. et al. (2021): A roadmap for the Human Developmental Cell Atlas. Nature 597(7875): 196–205. DOI: 10.1038/s41586-021-03620-1.
- Tyser, R. C. V.; Mahammadov, E.; Nakanoh, S.; Vallier, L.; Scialdone, A. & Srinivas, S. (2021): Single-cell transcriptomic characterization of a gastrulating human embryo. Nature 600(7888): 285–289. DOI: 10.1038/s41586-021-04158-y.
- Cao, J.; O’Day, D. R.; Pliner, H. A.; … & Shendure, J. (2020): A human cell atlas of fetal gene expression. Science 370(6518): eaba7721. DOI: 10.1126/science.aba7721.
- Domcke, S.; Hill, A. J.; Daza, R. M.; … & Shendure, J. (2020): A human cell atlas of fetal chromatin accessibility. Science 370(6518): eaba7612. DOI: 10.1126/science.aba7612.
- Suo, C.; Dann, E.; Goh, I.; … Haniffa, M.; Teichmann, S. A. et al. (2022): Mapping the developing human immune system across organs. Science 376(6597): eabo0510. DOI: 10.1126/science.abo0510.
- Popescu, D.-M.; Botting, R. A.; Stephenson, E.; … & Haniffa, M. (2019): Decoding human fetal liver haematopoiesis. Nature 574(7778): 365–371. DOI: 10.1038/s41586-019-1652-y.
- Braun, E.; Danan-Leon, M.; Hochgerner, H.; … & Linnarsson, S. (2023): Comprehensive cell atlas of the first-trimester developing human brain. Science 382(6667): eadf1226. DOI: 10.1126/science.adf1226.
- Zeng, B.; Liu, Z.; Lu, Y. et al. (2023): The single-cell and spatial transcriptional landscape of human gastrulation and early brain development. Cell Stem Cell 30(6): 851–866. DOI: 10.1016/j.stem.2023.04.016.
- Rood, J. E.; Wynne, S.; Robson, L.; Hupalowska, A.; Randell, J.; Teichmann, S. A. & Regev, A. (2025): The Human Cell Atlas from a cell census to a unified foundation model. Nature 637(8047): 1065–1071. DOI: 10.1038/s41586-024-08338-4.
Consortium websites:
- Human Cell Atlas — https://www.humancellatlas.org/
- HCA Development Biological Network — https://www.humancellatlas.org/biological-networks/development-biological-network/
- HuDeCA (France, INSERM) — https://hudeca.com/
See also
- Carnegie Stages — morphological complement to the HuDeCA cell resolution
- Embryo — personal-ontological classification of the integral organism
- Fertilization — CS 1, the personal-ontological starting point
- Gastrulation — CS 6–7, Tyser/Srinivas atlas
- Individuality — individuation debate with empirical HuDeCA linkage
- Synthetic Embryo Model — SCBEM benchmarking against the HuDeCA reference
- Fourteen-Day Rule — research rule in tension with HuDeCA relaxations
Generated by querying the Personhood ontology.