ArticleDevelopment (Cambridge, England)2014
Single-cell analyses of regulatory network perturbations using enhancer-targeting TALEs suggest novel roles for PU.1 during haematopoietic specification.
Article in Development (Cambridge, England), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 28 citations in OpenAlex.
- UnlockingNAR genomics and bioinformatics · 2026Article
- Article
- Towards a comprehensive regulatory map of Mammalian Genomes.Research square · 2023Article
- Activation of lineage competence in hemogenic endothelium precedes the formation of hematopoietic stem cell heterogeneity.Cell research · 2023Article
- Guiding T lymphopoiesis from pluripotent stem cells by defined transcription factors.Cell research · 2020Article
- Tracing the first hematopoietic stem cell generation in human embryo by single-cell RNA sequencing.Cell research · 2019Article
- Expanded potential stem cell media as a tool to study human developmental hematopoiesis in vitro.Experimental hematology · 2019Article
- SCNS: a graphical tool for reconstructing executable regulatory networks from single-cell genomic data.BMC systems biology · 2018Article
- Single cell analysis of normal and leukemic hematopoiesis.Molecular aspects of medicine · 2018Review
- Mammalian Transcription Factor Networks: Recent Advances in Interrogating Biological Complexity.Cell systems · 2017Review
- Cell cycle dynamics and complement expression distinguishes mature haematopoietic subsets arising from hemogenic endothelium.Cell cycle (Georgetown, Tex.) · 2017Article
- Blood: Education for stem cells.Nature · 2017Article
- PML/RARa inhibits PTEN expression in hematopoietic cells by competing with PU.1 transcriptional activity.Oncotarget · 2016Article
- Chromatin organization in pluripotent cells: emerging approaches to study and disrupt function.Briefings in functional genomics · 2016Review
- Article
- Genome-scale definition of the transcriptional programme associated with compromised PU.1 activity in acute myeloid leukaemia.Leukemia · 2016Article
- The RUNX1-PU.1 axis in the control of hematopoiesis.International journal of hematology · 2015Review
- Creating cellular diversity through transcription factor competition.The EMBO journal · 2015Article
- Transcription factor-mediated reprogramming toward hematopoietic stem cells.The EMBO journal · 2015Review
- GATA2(-/-) human ESCs undergo attenuated endothelial to hematopoietic transition and thereafter granulocyte commitment.Cell regeneration (London, England) · 2015Article
Corrections and comments
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Authors and funding
17 authors at 7 institutions in 2 countries.
Funding
Abstract
Transcription factors (TFs) act within wider regulatory networks to control cell identity and fate. Numerous TFs, including Scl (Tal1) and PU.1 (Spi1), are known regulators of developmental and adult haematopoiesis, but how they act within wider TF networks is still poorly understood. Transcription activator-like effectors (TALEs) are a novel class of genetic tool based on the modular DNA-binding domains of Xanthomonas TAL proteins, which enable DNA sequence-specific targeting and the manipulation of endogenous gene expression. Here, we report TALEs engineered to target the PU.1-14kb and Scl+40kb transcriptional enhancers as efficient new tools to perturb the expression of these key haematopoietic TFs. We confirmed the efficiency of these TALEs at the single-cell level using high-throughput RT-qPCR, which also allowed us to assess the consequences of both PU.1 activation and repression on wider TF networks during developmental haematopoiesis. Combined with comprehensive cellular assays, these experiments uncovered novel roles for PU.1 during early haematopoietic specification. Finally, transgenic mouse studies confirmed that the PU.1-14kb element is active at sites of definitive haematopoiesis in vivo and PU.1 is detectable in haemogenic endothelium and early committing blood cells. We therefore establish TALEs as powerful new tools to study the functionality of transcriptional networks that control developmental processes such as early haematopoiesis.
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