ArticleEMBO reports2021
A splicing factor switch controls hematopoietic lineage specification of pluripotent stem cells.
Article in EMBO reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 21 citations in OpenAlex.
- Mechanisms coordinating exit from the stem cell state in mammals.Genes & development · 2026Review
- The functional landscape of alternative splicing in hematopoietic lineage commitment.Nature communications · 2026Article
- RBFOX2-dependent alternative splicing of Numb regulates Notch signaling during muscle stem cell activation.Stem cell reports · 2026Article
- Alternative splicing in stem cells and development: research progress and emerging technologies.Cell regeneration (London, England) · 2025Review
- Splicing the Difference: Harnessing the Complexity of the Transcriptome in Hematopoiesis.Experimental hematology · 2024Review
- Function of serine/arginine-rich splicing factors in hematopoiesis and hematopoietic malignancies.Cancer cell international · 2024Review
- The splicing factor Prpf31 is required for hematopoietic stem and progenitor cell expansion during zebrafish embryogenesis.The Journal of biological chemistry · 2024Article
- Proteomics of novel induced pluripotent stem cell-derived vascular endothelial cells reveal extensive similarity with an immortalized human endothelial cell line.Physiological genomics · 2023Article
- Article
- Transcription factors and splice factors - interconnected regulators of stem cell differentiation.Current stem cell reports · 2023Article
- An RNAi screen of RNA helicases identifies eIF4A3 as a regulator of embryonic stem cell identity.Nucleic acids research · 2022Article
- Carm1 and the Epigenetic Control of Stem Cell Function.Stem cells translational medicine · 2022Article
- Article
- The role of NUMB/NUMB isoforms in cancer stem cells.BMB reports · 2021Review
- A splicing factor switch controls hematopoietic lineage specification of pluripotent stem cells.EMBO reports · 2021Article
Corrections and comments
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Authors and funding
18 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Alternative splicing (AS) leads to transcriptome diversity in eukaryotic cells and is one of the key regulators driving cellular differentiation. Although AS is of crucial importance for normal hematopoiesis and hematopoietic malignancies, its role in early hematopoietic development is still largely unknown. Here, by using high-throughput transcriptomic analyses, we show that pervasive and dynamic AS takes place during hematopoietic development of human pluripotent stem cells (hPSCs). We identify a splicing factor switch that occurs during the differentiation of mesodermal cells to endothelial progenitor cells (EPCs). Perturbation of this switch selectively impairs the emergence of EPCs and hemogenic endothelial progenitor cells (HEPs). Mechanistically, an EPC-induced alternative spliced isoform of NUMB dictates EPC specification by controlling NOTCH signaling. Furthermore, we demonstrate that the splicing factor SRSF2 regulates splicing of the EPC-induced NUMB isoform, and the SRSF2-NUMB-NOTCH splicing axis regulates EPC generation. The identification of this splicing factor switch provides a new molecular mechanism to control cell fate and lineage specification.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.