SAMHD1 knockout hiPSC model enables high lentiviral transduction efficiency in myeloid cell types Article Swipe
Huinan Li
,
Maliha Afroze
,
Gunisha Arora
,
Scot Federman
,
Kaivalya Shevade
,
Yeqing Angela Yang
,
Phuong T. Nguyen
,
Rustam Esanov
,
Laralynne Przybyla
,
Adam J. Litterman
,
Shawn Shafer
·
YOU?
·
· 2025
· Open Access
·
· DOI: https://doi.org/10.3389/fgene.2025.1574545
YOU?
·
· 2025
· Open Access
·
· DOI: https://doi.org/10.3389/fgene.2025.1574545
Recent advances in functional genomics tools have ushered in a new era of genetic editing to identify molecular pathways relevant to developmental and disease biology. However, limited model systems are available that adequately mimic cell states and phenotypes associated with human disease pathways. Here, we quantitatively analyzed the founder population bottleneck effect and demonstrated how the population changes from human induced pluripotent stem cells (hiPSCs) to hematopoietic stem cells and to the final induced macrophage population. We then engineered a key gene encoding an enzyme in the myeloid cell antiviral pathway- SAMHD1- knockout (KO) hiPSCs and characterized the hiPSC line with RNA-Seq and induced macrophages from two distinct protocols with functional analysis. We then generated SAMHD1 KO CRISPR-dCAS9 KRAB hiPSCs through lentiviral transduction aiming to increase the efficiency of lentiviral mediated gene transfer. We demonstrated increased lentiviral transduction efficiency in induced macrophages, as well as microglia induced with two distinct protocols. This model allows for efficient gene knockdown, as well as large-scale functional genomics screens in mature hiPSC-derived macrophages or microglia with applications in innate immunity and chronic inflammatory disease biology. These experiments highlight the broad applicability of this platform for disease-relevant target identification and may improve our ability to run large-scale screens in hiPSC-derived myeloid model systems.
Related Topics
Concepts
Transduction (biophysics)
Cell biology
SAMHD1
Biology
Computational biology
Myeloid
Cell
Gene
Genetics
Cancer research
Biophysics
Reverse transcriptase
RNA
Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.3389/fgene.2025.1574545
- https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2025.1574545/pdf
- OA Status
- gold
- References
- 38
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4409206227
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W4409206227Canonical identifier for this work in OpenAlex
- DOI
-
https://doi.org/10.3389/fgene.2025.1574545Digital Object Identifier
- Title
-
SAMHD1 knockout hiPSC model enables high lentiviral transduction efficiency in myeloid cell typesWork title
- Type
-
articleOpenAlex work type
- Language
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enPrimary language
- Publication year
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2025Year of publication
- Publication date
-
2025-04-07Full publication date if available
- Authors
-
Huinan Li, Maliha Afroze, Gunisha Arora, Scot Federman, Kaivalya Shevade, Yeqing Angela Yang, Phuong T. Nguyen, Rustam Esanov, Laralynne Przybyla, Adam J. Litterman, Shawn ShaferList of authors in order
- Landing page
-
https://doi.org/10.3389/fgene.2025.1574545Publisher landing page
- PDF URL
-
https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2025.1574545/pdfDirect link to full text PDF
- Open access
-
YesWhether a free full text is available
- OA status
-
goldOpen access status per OpenAlex
- OA URL
-
https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2025.1574545/pdfDirect OA link when available
- Concepts
-
Transduction (biophysics), Cell biology, SAMHD1, Biology, Computational biology, Myeloid, Cell, Gene, Genetics, Cancer research, Biophysics, Reverse transcriptase, RNATop concepts (fields/topics) attached by OpenAlex
- Cited by
-
0Total citation count in OpenAlex
- References (count)
-
38Number of works referenced by this work
- Related works (count)
-
10Other works algorithmically related by OpenAlex
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