HCA Data Explorer

Mapping the developing human immune system across organs

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Updated October 1, 2022

Recent advances in single cell genomics technologies have facilitated studies on the developing immune system at unprecedented scale and resolution. However, these studies have focused on one or a few organs and were thus limited in understanding the developing immune system as a distributed network across tissues. Here, we profiled prenatal haematopoietic organs, lymphoid organs and non-lymphoid tissues using a combination of single-cell RNA sequencing, paired antigen-receptor sequencing and spatial transcriptomics to reconstruct the developing human immune system. Our analysis revealed the acquisition of immune effector transcriptome profiles in macrophages, mast cells and NK cells from the second trimester, and the transcriptomic changes accompanying the late-stage maturation of developing monocytes and T cells that extended from their organ of origin to peripheral tissues. We uncovered system-wide blood and immune cell development beyond the conventional primary haematopoietic organs. We further identified, extensively characterised and functionally validated the human prenatal B1 cells. Finally, we provide evidence for thymocyte-thymocyte selection origin for αβTCR- expressing unconventional T cells based on TCR gene usage and an in vitro artificial thymic organoid culture model. Our comprehensive atlas of the developing human immune system provides both valuable data resources and biological insights that will facilitate cell engineering, regenerative medicine and disease understanding. One-Sentence Summary By performing a comprehensive single-cell RNA sequencing atlas of human developing immune system together with antigen-receptor sequencing and spatial transcriptomics, we explored the cross-gestation and cross-organ variability in immune cells, discovered system-wide blood and immune cell development, identified, characterised and functionally validated the properties of human prenatal B1 cells and the origin of unconventional T cells.

Menna ClatworthyWellcome Sanger Institute, Wellcome Genome Campusmrc38@cam.ac.uk
Muzlifah HaniffaWellcome Sanger Institute, Wellcome Genome Campusm.a.haniffa@newcastle.ac.uk
Sarah TeichmannWellcome Sanger Institute, Wellcome Genome Campusst9@sanger.ac.uk
Chenqu Suo1
Emma Dann1
Issac Goh2
Laura Jardine2
Vitalii Kleshchevnikov1
Jong-Eun Park1
Rachel Botting2
Emily Stephenson2
Justin Engelbert2
Zewen Kelvin Tuong1
Krzysztof Polanski1
Nadav Yayon1
Chuan Xu1
Ondrej Suchanek3
Rasa Elmentaite1
Cecilia Domínguez Conde1
Peng He1
Sophie Pritchard1
Mohi Miah4
Corina Moldovan5
Alexander Steemers1
Martin Prete1
John Marioni1
Menna Clatworthy1
Muzlifah Haniffa1
Sarah Teichmann1
1Wellcome Sanger Institute, Wellcome Genome Campus
2Newcastle University, Newcastle upon Tyne
3University of Cambridge Department of Medicine; Cambridge, UK
4Newcastle University; Newcastle upon Tyne
5Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne
Ami Day

To reference this project, please use the following link:

https://explore.data.humancellatlas.org/projects/fcaa53cd-ba57-4bfe-af9c-eaa958f95c1a

Supplementary links are provided by contributors and represent items such as additional data which can’t be hosted here; code that was used to analyze this data; or tools and visualizations associated with this specific dataset.

1.https://developmental.cellatlas.io/fetal-immune
INSDC Project Accessions:
ERP135635, ERP137429, ERP135310
Array Express Accessions:INSDC Study Accessions:

Analysis Portals

CZ CELLxGENECZ CELLxGENE
UCSC Cell BrowserUCSC Cell Browser

Project Label

DevelopingImmuneSystem

Species

2 species

Sample Type

2 sample types

Anatomical Entity

10 anatomical entities

Organ Part

Unspecified

Selected Cell Types

Unspecified

Model Organ

Thymus

Disease Status (Specimen)

normal

Disease Status (Donor)

normal

Development Stage

4 development stages

Library Construction Method

5 library construction methods

Nucleic Acid Source

2 nucleic acid sources

Paired End

false

Analysis Protocol

analysis_protocol_cell_type_assignment, analysis_protocol_scRNA-Seq, analysis_protocol_visium

File Format

5 file formats

Cell Count Estimate

922.3k

Donor Count

30
csv1 file(s)fastq.gz579 file(s)h5ad8 file(s)tiff15 file(s)xlsx1 file(s)