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Reprogramming Committed Murine Blood Cells to Induced Hematopoietic Stem Cells with Defined Factors
Open accessAbstract
Hematopoietic stem cells (HSCs) sustain blood formation throughout life and are the functional units of bone marrow transplantation. We show that transient expression of six transcription factors Run1t1, Hlf, Lmo2, Prdm5, Pbx1, and Zfp37 imparts multilineage transplantation potential onto otherwise committed lymphoid and myeloid progenitors and myeloid effector cells. Inclusion of Mycn and Meis1 and use of polycistronic viruses increase reprogramming efficacy. The reprogrammed cells, designated induced-HSCs (iHSCs), possess clonal multilineage differentiation potential, reconstitute stem/progenitor compartments, and are serially transplantable. Single-cell analysis revealed that iHSCs derived under optimal conditions exhibit a gene expression profile that is highly similar to endogenous HSCs. These findings demonstrate that expression of a set of defined factors is sufficient to activate the gene networks governing HSC functional identity in committed blood cells. Our results raise the prospect that blood cell reprogramming may be a strategy for derivation of transplantable stem cells for clinical application.
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“enforced expression of transcription factors or microRNAs has been shown to be able to generate transplantable stem cells from committed cell types.[102][103][104]”
From Aging of hematopoietic stem cells (2018) · cites this paper as [102]
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Metadata
- Authors
- Riddell, J., Gazit, R., Garrison, B. S., Guo, G., Saadatpour, A., Mandal, P. K., Ebina, W., Volchkov, P., Yuan, G.-C., Orkin, S. H., & Rossi, D. J.
- Affiliations
- Boston Children's Hospital (US)
- Harvard University (US)
- Corresponding author
- Rossi, Derrick J.
- ORCID
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2014-04
- Volume
- 157
- Issue
- 3
- Pages
- 549-564
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC4060823
- OpenAlex
- W1963745085
- Cited by
- 323
- References
- 41
- Citations by year
- 2026: 5 · 2025: 8 · 2024: 14 · 2023: 10 · 2022: 16 · 2021: 24 · 2020: 16 · 2019: 28 · 2018: 33 · 2017: 41 · 2016: 54 · 2015: 48 · 2014: 25
- FWCI
- 39.72
- Type
- journal article
- Language
- en
- Update notices
- erratum (2014-07-03)
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Howard Hughes Medical Institute
- National Institute on Aging (R00AG029760, K99AG029760)
- National Heart, Lung, and Blood Institute (U01HL1000001, U01HL107440, U01HL100001, R01HL107630)
- National Institute of Diabetes and Digestive and Kidney Diseases (U01DK072473)
- Topics
- Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Mesenchymal stem cell research
- Keywords
- hematopoietic stem cells, transcription factors, HLF, LMO2, PRDM5, PBX1, MYCN, MEIS1, multilineage differentiation, lymphoid progenitors, myeloid progenitor cells, stem cell transplantation, gene expression profiling
- MeSH terms
- N-Myc Proto-Oncogene Protein, Myeloid Ecotropic Viral Integration Site 1 Protein, Animals, Hematopoietic Stem Cells, Mice, Inbred C57BL, Neoplasm Proteins, Proto-Oncogene Proteins, Transcription Factors, Hematopoietic Stem Cell Transplantation, Homeodomain Proteins, Mice, Single-Cell Analysis, Transcriptome, Cellular Reprogramming
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