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Related Concept Videos

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Combinatorial gene control is the synergistic action of several transcriptional factors to regulate the expression of a single gene. The absence of one or more of these factors may lead to a significant difference in the level of gene expression or repression.
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Related Experiment Video

Updated: Jan 18, 2026

Hemogenic Reprogramming of Human Fibroblasts by Enforced Expression of Transcription Factors
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A combinatorial transcription factor screening platform for immune cell reprogramming.

Ilia Kurochkin1, Abigail R Altman1, Inês Caiado2

  • 1Molecular Medicine and Gene Therapy, Science for Life Laboratory, Lund Stem Cell Center, Lund University, BMC A12, 221 84 Lund, Sweden; Wallenberg Centre for Molecular Medicine, Lund University, BMC A12, 221 84 Lund, Sweden.

Cell Systems
|January 15, 2026
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Summary
This summary is machine-generated.

Researchers developed REPROcode, a platform for immune cell reprogramming. This tool identifies transcription factor (TF) combinations to engineer immune cells for advanced immunotherapy applications.

Keywords:
antigen-presenting cellsbarcodingcellular reprogrammingcombinatorial screeningdendritic cellsinnate lymphoid cellsmachine learningtranscription factortranscriptional hierarchy

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Area of Science:

  • Immunology
  • Molecular Biology
  • Bioengineering

Background:

  • Direct reprogramming of immune cells offers therapeutic potential but is hindered by incomplete understanding of transcription factor (TF) networks.
  • Identifying effective TF combinations is crucial for advancing immunotherapy strategies.

Purpose of the Study:

  • To develop and validate REPROcode, a novel platform for combinatorial screening of TFs to identify combinations for immune cell reprogramming.
  • To explore the broader reprogramming capacity of immune TFs and construct a TF hierarchy map.

Main Methods:

  • Development of REPROcode, a single-cell screening platform utilizing multiplexed TF sets.
  • Construction and screening of an arrayed lentiviral library of 408 barcoded immune TFs.
  • Validation of REPROcode by inducing specific immune cell types like cDC1s and NK-like cells.

Main Results:

  • REPROcode successfully identified optimal TF stoichiometry, fidelity enhancers, and regulators for cDC1 induction.
  • Screening revealed myeloid and lymphoid phenotypes, leading to the creation of a TF hierarchy map.
  • The platform demonstrated its discovery power by successfully inducing natural killer (NK)-like cells.

Conclusions:

  • REPROcode is a versatile toolbox for engineering immune cells, significantly advancing immunotherapy research.
  • This study enhances the understanding of immune transcriptional control and TF networks.
  • The developed TF hierarchy map provides guidance for future immune cell reprogramming efforts.