Table 2 Summary of the biological applications of sc-CRISPR

Hematology/leukemia

CROP-seq [46]

Studying TCR signaling by perturbation of transcription factors and regulators of TCR signaling in T lymphocytes

Perturb-seq [43, 44]

Characterizing the different branches of the unfolded protein response (controlled by IRE1a, ATF6 and PERK) after pharmacological UPR induction

Transcriptional response of BMDCs to LPS stimulation

Impact of perturbation of transcription factors and cell cycle regulators on myeloid cell state

CRISP-seq [45]

Studying regulators of myeloid development and identifying cell-type-specific functions

sc-Tiling [106]

Identification of functional protein domains by tiling the exons of methyltransferase DOTL1 in leukemia

POKI-seq [143]

Enhancing T cell fitness and anti-tumor immunity by pooled knock-in in the TCR locus

(bee)STING-seq [107]

Mapping GWAS loci in candidate cis-regulatory elements in erythroid cells for their impact on blood traits

CaRPool-seq [104]

Studying regulators of myeloid differentiation in the context of AML

TAP-seq [84]

Perturbation of active enhancers on chromosome 8 and 11 to map relationships between enhancers and their target genes

Distinguishing the different cell types in murine bone marrow cells based on gene expression

Perturb-ATAC [101]

Regulation of keratinocyte and B cell fate by transcription factors, epigenetic regulators and non-coding RNAs

CRISPR-sciATAC [124]

Perturbation of epigenetic regulators and their impact on chromatin accessibility in myeloid leukemia cells

SPEAR-ATAC [125]

Mapping the epigenetic impact of transcription factors in myeloid differentiation

Compressed perturb-seq [103]

Analyzing the immune response of monocytic leukemia cells upon LPS stimulation

Norman et al. [49]

Studying regulation of erythroid differentiation

Belk et al. [52]

Targeting the epigenetic INO80 and BAF complexes to study T cell exhaustion of tumor infiltrating lymphocytes

Giladi et al. [53]

Defining the role of myeloid transcription factors in regulation of hematopoietic stem cell differentiation and progenitor cell states

Rothenberg et al. [144]

Describing the role of hematopoietic transcription factors during T cell development and commitment

Other models

Direct-seq [73]

Establishing a flexible approach for gRNA capture using an 8A8G tag

Direct-capture Perturb-seq [74]

Studying genes involved in UPR pathway, cholesterol biosynthesis, DNA repair

Mosaic-seq [47]

Characterizing the contribution of enhancer activity to gene expression

sc-eVIP [111]*

Analysis of the phenotypic impact (GOF or LOF) of coding variants in TP53 and KRAS in a lung cancer model

Deaminase screening [108]

Screening for candidate resistance mutations for vemurafenib in melanoma

Perturb-CITE-seq [132]

Identification of resistance mechanisms to immune checkpoint inhibition, such as loss of certain surface markers causing immune evasion

ECCITE-seq [131]

Resolving different cell types and samples based on hashtags, transcriptomes and surface proteins, with the possibility to also capture gRNA

Perturb-map [123]

Assessing lung cancer growth and tumor microenvironment after perturbation of cytokine signaling and other immune pathways

PerturbSci-Kinetics [140]

Evaluating transcriptional dynamics regulated by genes involved in transcription initiation, chromatin remodeling, DNA replication and RNA processing

In vivo Perturb-seq [113]

Perturbing candidate risk genes for autism or neurodevelopmental disorders in the developing brain in utero

Genome-wide Perturb-seq [136]

Characterization of uncharacterized genes and describing new gene functions

DoNick-seq [54]

Studying mTORC1 regulators in conditions of amino acid starvation

Genga et al. [48]

identifying drivers of endoderm differentiation

Tian et al. [50]

Validation of hit genes from genome-wide CRISPR screen which are associated with neurodegenerative diseases

Alda-Catalinas et al.[51]

Characterizing the processes of zygotic genome activation