Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Pooled combinatorial screening identifies transcription factor sets that drive hematopoietic progenitor-like cell fate

ABSTRACT: Mammalian cells can be directed towards specific fates by overexpression of transcription factors (TFs). However, discovering and optimizing which TFs in combination produce a state of interest remains challenging. Here, we develop a scalable screening platform that addresses this challenge by combining high-MOI pooled delivery of barcoded TF ORFs, data augmentation, targeted cell enrichments, and single-cell transcriptomic readouts. As proof of principle, we apply the platform to optimize the generation of hematopoietic stem and progenitor-like cells (HSPCs) from human embryonic stem cells. Our data demonstrate technical performance across a range of key metrics and reveal a richly structured reprogramming fitness landscape over millions of TF combinations. In silico optimization of HSPC-similarity metrics over this landscape revealed two TF combinations that demonstrate superior potency in generating naïve multipotent hematopoietic progenitors relative to gold-standard controls. This study demonstrates a powerful approach for data-driven cell fate engineering using complex combinatorial perturbations.

ORGANISM(S): Homo sapiens

PROVIDER: GSE328457 | GEO | 2026/07/12

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

CUX1 recruits SWI/SNF to promote chromatin accessibility in human hematopoietic cells

Project description:Transcription factors(TF) plays a key role in hematopoiesis via promoting cell-type specific gene expression. A subset of TFs, canonically termed “pioneer factors”, possesses the ability to bind to otherwise inaccessible heterochromatin regions, and recruit additional TFs, co-activators, and chromatin remodelers to establish activating/repressive cis-regulatory elements(CRE). To date, few of these TFs with pioneer activity has been elucidated in hematopoiesis. CUX1, a homeobox containing TF frequently mutated in a range of hematological malignancies, has been reported to regulate essential cellular processes and regulate myeloid vs erythroid differentiation. However, the molecular mechanism governing its transcriptional function remains unclear. Using a multi-faceted functional genomic approach, we discovered that CUX1 interacts and recruits the chromatin remodeler SWI/SNF to distal enhancers in both lymphoblast K562 cell line and primary human HSPC. The interaction promotes an accessible state of chromatin, changes in nucleosome positioning and transcriptional programs. We also discovered that the CUX1 & SWI/SNF binding sites are co-occupied by other hematopoietic transcriptional factors. Together this revealed a unique mechanism of CUX1’s regulatory function in hematopoietic development: it recruits SWI/SNF chromatin remodeler to distal enhancers, establish an accessible chromatin landscape and enabled other hematopoietic TFs to bind and activates cell-type specific gene expression programs.

2026-03-16 | PXD037838 | Pride

TF co-binding to nucleosome arrays

Project description:Cell type maintenance and conversion require the combined action of transcription factors (TFs), but the underlying principles remain elusive. Here, we investigated how four TF combinations lead to different reprogramming outputs by studying TF occupancy, nucleosome positioning, and genome 3D organization. We reveal that TF combinations target nucleosome with distinct 3D nucleosome conformations. We also reveal that TFs employ different motif readout mechanisms to reach their cell type specific targets. Moreover, the ability of pioneer TFs to enable non-pioneer factors the access to closed chromatin is markedly different across combinations. Overall, our findings uncover distinct modes of action for TFs during reprogramming.

2024-09-27 | GSE201852 | GEO

A combinatorial transcription factor screening platform for immune cell reprogramming [bulkRNA-seq]

Project description:Direct reprogramming of immune cells holds promise for immunotherapy but is constrained by limited knowledge of transcription factor (TF) networks. Here, we developed REPROcode, a combinatorial single-cell screening platform to identify TF combinations for immune cell reprogramming. We first validated REPROcode by inducing Type-1 Conventional Dendritic Cells (cDC1) with multiplexed sets of 9, 22, and 42 factors. With cDC1-enriched TFs, REPROcode enabled identification of optimal TF stoichiometry, fidelity enhancers, and regulators of cDC1 states. We then constructed an arrayed lentiviral library of 408 barcoded immune TFs to explore broader reprogramming capacity. Screening 48 TFs enriched in dendritic cell subsets yielded myeloid and lymphoid phenotypes and enabled the construction of a TF hierarchy map to guide immune reprogramming. Finally, we validated REPROcode’s discovery power by inducing Natural Killer (NK)-like cells. This study deepens our understanding of immune transcriptional control and provides a versatile toolbox for engineering immune cells to advance immunotherapy.

2026-01-14 | GSE298487 | GEO

A combinatorial transcription factor screening platform for immune cell reprogramming [scRNA-seq]

2026-01-14 | GSE298471 | GEO

Genome-wide Transcription Factor binding maps reveal cell-specific changes in the regulatory architecture of human HSPC [ChIPmentation]

Project description:Hematopoietic stem and progenitor cells (HSPCs) rely on a complex interplay of transcription factors (TFs) to regulate their differentiation into mature blood cells. A heptad of TFs - FLI1, ERG, GATA2, RUNX1, TAL1, LYL1, LMO2 - has been shown to bind to regulatory elements in bulk CD34+ HSPCs. However, whether specific combinations of these TFs have distinct roles in regulating hematopoietic differentiation remained unknown. In this study, we mapped the genome-wide binding profiles of these TFs and other chromatin-associated markers in distinct HSPC subsets (HSC, CMP, GMP, MEP). We found that the heptad occupancy and enhancer-promoter interactions varied significantly across cell types and were associated with cell-type specific gene expression. Moreover, we observed distinct regulatory elements that were enriched with specific combinations of TFs, such as stem-cell specific elements with ERG, and myeloid and megakaryocyte-erythroid specific elements with combinations of FLI1, RUNX1, GATA2, TAL1, LYL1, and LMO2. These findings suggest that specific combinations of TFs play critical roles in the regulation of hematopoietic differentiation, and provide a valuable resource for the development of targeted therapies to manipulate specific HSPC subsets.

2023-08-21 | GSE231422 | GEO

Genome-wide Transcription Factor binding maps reveal cell-specific changes in the regulatory architecture of human HSPC [HiChIP]

2023-08-21 | GSE231426 | GEO

Genome-wide Transcription Factor binding maps reveal cell-specific changes in the regulatory architecture of human HSPC [ChIP-seq]

2023-08-21 | GSE231425 | GEO

Genome-wide Transcription Factor binding maps reveal cell-specific changes in the regulatory architecture of human HSPC [HiC]

2023-08-21 | GSE231485 | GEO

An autoinhibitory switch of the LSD1 disordered region controls enhancer silencing

Project description:Transcriptional coregulators and transcription factors (TFs) contain intrinsically disordered regions (IDRs) that are critical for their partitioning and function in gene regulation. Canonically, IDRs drive coregulator-TF association by directly promoting multivalent protein-protein interactions. Using a chemical genetic approach, we report an unexpected mechanism by which the IDR of the corepressor LSD1 excludes TF association, acting as a dynamic conformational switch that tunes repression of active cis-regulatory elements. Hydrogen-deuterium exchange shows that the LSD1 IDR interconverts between transient open and closed conformational states, the latter of which inhibits partitioning of the proteins structured domains with TF hubs. This autoinhibitory switch controls leukemic differentiation by modulating repression of active cis-regulatory elements bound by LSD1 and master hematopoietic TFs. Together, these studies unveil that the dynamic crosstalk between opposing structured and unstructured regions is an alternative paradigm by which disordered regions can shape coregulator-transcription factor interactions to control cis-regulatory landscapes and cell fate.

2024-03-05 | MSV000094239 | MassIVE

Title: A SWI/SNF-specific Ig-like domain, SWIFT, is a transcription factor binding platform

Project description:Mammalian SWI/SNF (BAF) chromatin remodeling complexes modulate DNA accessibility and gene expression, however, the mechanisms by which they are targeted on chromatin remain incompletely understood. Here, we define SWIFT (SWI/SNF Ig-Fold for Transcription Factor Interactions), found on the SMARCD family of subunits within the core module as an evolutionarily conserved, broad transcription factor (TF) binding platform. SWIFT is necessary and sufficient for direct interaction with the transactivation domain of a lineage-specific TF, PU.1, in vitro and in cells, with a single amino acid mutation in SWIFT able to disrupt PU.1-mSWI/SNF binding, inhibit site-specific complex targeting and activity, and attenuate oncogenic gene expression and proliferation of PU.1-dependent cancer cells. Dominant expression of SWIFT in isolation across cell types sequesters mSWI/SNF-interacting TFs and poisons TF-addicted cancer cells. Finally, TFs interact with SWIFT in a SMARCD paralog-specific manner, informing approaches for modulation of cell type- and disease-specific transcription.

2025-12-31 | PXD070375 | Pride

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data