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| Status |
Public on Oct 01, 2023 |
| Title |
Single-cell Architecture and Functional Requirement of Alternative Splicing during Hematopoietic Stem Cell Emergence [RNA-Seq] |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Hematopoietic stem cells (HSCs) are well known to generate from a rare hemogenic population of embryonic endothelial cells through a dynamic fate transition, accompanied by widespread changes in gene regulatory networks. Nevertheless, RNA splicing, a striking feature in shaping transcriptome and enabling the generation of vast transcripts and diverse proteins, has never been illustrated in this transient endothelial to HSC conversion. Here, we constructed an isoform-based transcriptome landscape during HSC development at single-cell resolution, which enables the identification of hemogenic signature isoforms, as well as stage-specific splicing events. Combining with functional screening, we showed that the inclusion of such hemogenic-specific exons was essential for hemogenic function in vitro. Moreover, their gradual appearance along with HSC specification from endothelial cells was orchestrated by the splicing regulator Srsf2. Therefore, early Srsf2 deficiency from endothelia cells dramatically impaired the HSC generation, which was accompanied by changes in the splicing pattern of several master hematopoietic regulators. These results redefine our understanding of the dynamic transcriptome diversity and demonstrate that the elaborate control of splicing governs cell fate in HSC formation.
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| Overall design |
Single-cell full-length RNA-sequencing of EC-associated cell populations.
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| Contributor(s) |
Wang F, Tan P, Zhang P, Ren Y, Zhou J, Wang D, Liu B, Lan Y, Yu J |
| Citation(s) |
34995116 |
| |
| Submission date |
Oct 08, 2021 |
| Last update date |
Dec 31, 2023 |
| Contact name |
Jia Yu |
| E-mail(s) |
j-yu@ibms.pumc.edu.cn
|
| Organization name |
Peking Union Medical College
|
| Street address |
Dong Dan San Tiao 5, Dongcheng District
|
| City |
Beijing |
| ZIP/Postal code |
100005 |
| Country |
China |
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| Platforms (1) |
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| Samples (48)
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| This SubSeries is part of SuperSeries: |
| GSE185555 |
Single-cell Architecture and Functional Requirement of Alternative Splicing during Hematopoietic Stem Cell Emergence |
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| Relations |
| BioProject |
PRJNA769638 |
| SRA |
SRP340514 |
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