 |
 |
GEO help: Mouse over screen elements for information. |
|
| Status |
Public on Jul 13, 2023 |
| Title |
IL-7 receptor signaling drives human B-cell precursor differentiation and expansion |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
Whereas absence of interleukin 7 (IL-7) signaling completely abrogates T and B lymphopoiesis in mice, severe combined immunodeficiency patients with mutations in the IL-7 receptor α chain still generate peripheral blood B cells. Consequently, human B lymphopoiesis has been thought to be independent of IL-7 signaling. Using flow cytometric analysis and single-cell RNA sequencing of bone marrow samples of IL-7 receptor α chain-deficient patients and healthy controls in combination with in vitro modeling of human B-cell differentiation, we demonstrate that IL-7 receptor signaling has a crucial role in human B lymphopoiesis. IL-7 drives proliferation and expansion of early B-cell progenitors, but not of pre-BII large cells. In addition, IL-7 has a limited role in the prevention of cell death. Furthermore, IL-7 guides cell fate decisions by enhancing the expression of BACH2, EBF1, and PAX5, which jointly orchestrate specification and commitment of early B-cell progenitors. In line with this observation, early B-cell progenitors of IL-7Rα-deficient patients still expressed myeloid-specific genes. Collectively, our results unveil a thus-far unknown role for IL-7 signaling in promoting the B-lymphoid fate and expanding early human B-cell progenitors, while defining important differences between mice and humans. Our results have implications for hematopoietic stem cell transplantation strategies in patients with T- B+ severe combined immunodeficiency and provide insights into the role of IL-7 receptor signaling in leukemogenesis.
|
| |
|
| Overall design |
Sorted mononuclear cells from bone marrow of two healthy donors and two patients with IL7RA deficiency were stained with CITEseq antibodies (IL7RA, CD34, CD19 and IgM) and analyzed using scRNAseq
|
| Web link |
https://ashpublications.org/blood/article/doi/10.1182/blood.2023019721/496603/IL-7-receptor-signaling-drives-human-B-cell?searchresult=1
|
| |
|
| Contributor(s) |
Kaiser F, Janowska I, Menafra R, de Gier M, Korzhenevich J, Pico-Knijnenburg I, Khatri I, Schulz A, Kuijpers T, Lankester A, Konstantinidis L, Erlacher M, Kloet S, van Schouwenburg P, Rizzi M, van der Burg M |
| Citation(s) |
37369082 |
| |
| Submission date |
Oct 03, 2022 |
| Last update date |
Jul 14, 2023 |
| Contact name |
Mirjam van der Burg |
| E-mail(s) |
[email protected]
|
| Phone |
+31647181911
|
| Organization name |
LUMC
|
| Street address |
Albinusdreef 2
|
| City |
Leiden |
| ZIP/Postal code |
2333 ZA Leiden |
| Country |
Netherlands |
| |
|
| Platforms (1) |
| GPL24676 |
Illumina NovaSeq 6000 (Homo sapiens) |
|
| Samples (8)
|
|
| Relations |
| BioProject |
PRJNA886683 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE214693_RAW.tar |
40.0 Mb |
(http)(custom) |
TAR (of MTX, TSV) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
|
|
|
|
 |
Less...
More...