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| Status |
Public on Jul 09, 2021 |
| Title |
Blood and immune cell development in human fetal bone marrow and in Down syndrome |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
Other
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| Summary |
Throughout postnatal life, haematopoiesis in the bone marrow (BM) maintains blood and immune cell production. Haematopoiesis first emerges in human BM at 11-12 post conception weeks while fetal liver (FL) haematopoiesis is still expanding. Yet, almost nothing is known about how fetal BM evolves to meet the highly specialised needs of the fetus and newborn infant. Here, we detail the development of fetal BM including stroma using single cell RNA-sequencing. We find that the full blood and immune cell repertoire is established in fetal BM in a short time window of 6-7 weeks early in the second trimester. Fetal BM promotes rapid and extensive diversification of myeloid cells, with granulocytes, eosinophils and dendritic cell subsets emerging for the first time. B-lymphocytes expansion occurs, in contrast with erythroid predominance in FL at the same gestational age. We identify transcriptional and functional differences that underlie tissue-specific identity and cellular diversification in fetal BM and FL. Finally, we reveal selective disruption of B-lymphocyte, erythroid and myeloid development due to cell intrinsic differentiation bias as well as extrinsic regulation through an altered microenvironment in the fetal BM from constitutional chromosome anomaly Down syndrome during this crucial developmental time window.
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| Overall design |
Sample RBG33493 is a pool of MNCs from three stage 3 fetal bone marrow samples (F90, F103, F107). Sample RBG33494 is a pool of CD34+ cells from two adult bone marrow samples (CIMA-60, CIMA-58) and one stage 3 fetal bone marrow sample (F103). Sample RBG33496 is a pool of CD34+ cells from two adult bone marrow samples (CIMA-90, CIMA-100) and one stage 3 fetal bone marrow sample (F107). Sample RBG33500 is a pool of CD34+ cells from two stage 2 fetal liver samples (F94 and F96) and one stage 1 fetal liver sample (F109). Sample RBG33503 is CD34+ cells from a one stage 2 fetal bone marrow sample (F96). Samples RBG33507 and RBG33508 are technical replicates of a pool of CD34+ cells from three stage 3 fetal liver samples (F90, F103, F107). Sample RBG31066 is a pool of CD34+ cells from four new born cord blood samples (XN3392). Individuals not analysed for this article - CIMA-60, CIMA-58, CIMA-90, CIMA-100, F94 and F109.
Supplementary_files_format_and_content:
ADT_DSBnormalised_postmRNAoverlap_CD34Sinu.csv.gz: CD34+ sinusoidal EC DSB normalised counts.
overlap_ADTonmRNA_DSBnormalised_FBM-MNCs.csv.gz: FBM EC DSB normalised counts.
overlap_ADTonmRNA_raw_FBM-MNCs.csv.gz: RAW protein - Post overlap with mRNA FBM MNCs.
overlap_ADTonmRNADSBnormalised_FL-FBM-CB.csv.gz: CD34+ progenitor EC DSB normalised counts.
overlap_ADTonmRNAraw_FL-FBM-CB.csv.gz: RAW Protein - Post QC + post overlap with demultiplexed mRNA Combination of FL-FBM-CB.
postQC_ADT_raw_FBM-MNCs.csv.gz: RAW protein - Post-QC FBM MNCs.
postQC_mRNAraw_FBM-MNCs.csv.gz: RAW mRNA - Post QC (+post doublet removal) FBM MNCs.
postQC_mRNAraw_FL-FBM-CB.csv.gz: RAW mRNA - Post QC (post doublet removal, post demultiplexing when needed) Combination of FL-FBM-CB.
preQC_ADTraw_FBM-MNCs.csv.gz: RAW protein - Post-CITE-seq-Count (pre-QC) FBM MNCs.
preQC_ADTraw_FL-FBM-CB.csv.gz: RAW Protein - Post-CITE-seq-Count (pre-QC) Combination of FL-FBM-CB.
preQC_mRNAraw_FBM-MNCs.csv.gz: RAW mRNA - Post-cell ranger (pre-QC) FBM MNCs.
preQC_mRNAraw_FL-FBM-CB.csv.gz: RAW mRNA - Post-cell ranger (pre-QC) Combination of FL-FBM-CB.
Raw_ADT_CD34Sinu_FLFBM.csv.gz: RAW Protein - Expression data.
Raw_mRNA_CD34Sinu_FLFBM.csv.gz: RAW mRNA - Sinusoidal endo RNA.
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| Contributor(s) |
Hannah R, Wilson NK, Quiroga Londoño M |
| Citation(s) |
34588693 |
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| Submission date |
Feb 16, 2021 |
| Last update date |
Oct 08, 2021 |
| Contact name |
Bertie Gottgens |
| E-mail(s) |
bg200@cam.ac.uk
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| Organization name |
University of Cambridge
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| Street address |
Jeffrey Cheah Biomedical Centre
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| City |
Cambridge |
| ZIP/Postal code |
CB2 0AW |
| Country |
United Kingdom |
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| Platforms (1) |
| GPL24676 |
Illumina NovaSeq 6000 (Homo sapiens) |
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| Samples (16)
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| Relations |
| BioProject |
PRJNA702168 |
| SRA |
SRP306736 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE166895_ADT_DSBnormalised_postmRNAoverlap_CD34Sinu.csv.gz |
672.2 Kb |
(ftp)(http) |
CSV |
| GSE166895_Raw_ADT_CD34Sinu_FLFBM.csv.gz |
216.4 Kb |
(ftp)(http) |
CSV |
| GSE166895_Raw_mRNA_CD34Sinu_FLFBM.csv.gz |
3.2 Mb |
(ftp)(http) |
CSV |
| GSE166895_overlap_ADTonmRNADSBnormalised_FL-FBM-CB.csv.gz |
10.2 Mb |
(ftp)(http) |
CSV |
| GSE166895_overlap_ADTonmRNA_DSBnormalised_FBM-MNCs.csv.gz |
3.3 Mb |
(ftp)(http) |
CSV |
| GSE166895_overlap_ADTonmRNA_raw_FBM-MNCs.csv.gz |
1.0 Mb |
(ftp)(http) |
CSV |
| GSE166895_overlap_ADTonmRNAraw_FL-FBM-CB.csv.gz |
3.2 Mb |
(ftp)(http) |
CSV |
| GSE166895_postQC_ADT_raw_FBM-MNCs.csv.gz |
1.3 Mb |
(ftp)(http) |
CSV |
| GSE166895_postQC_mRNAraw_FBM-MNCs.csv.gz |
41.7 Mb |
(ftp)(http) |
CSV |
| GSE166895_postQC_mRNAraw_FL-FBM-CB.csv.gz |
154.6 Mb |
(ftp)(http) |
CSV |
| GSE166895_preQC_ADTraw_FBM-MNCs.csv.gz |
2.9 Mb |
(ftp)(http) |
CSV |
| GSE166895_preQC_ADTraw_FL-FBM-CB.csv.gz |
16.3 Mb |
(ftp)(http) |
CSV |
| GSE166895_preQC_mRNAraw_FBM-MNCs.csv.gz |
49.4 Mb |
(ftp)(http) |
CSV |
| GSE166895_preQC_mRNAraw_FL-FBM-CB.csv.gz |
393.0 Mb |
(ftp)(http) |
CSV |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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