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Updated: Aug 6, 2025
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Directed Differentiation of Primitive and Definitive Hematopoietic Progenitors from Human Pluripotent Stem Cells
Published on: November 1, 2017
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Lymphoid cell development from fetal hematopoietic progenitors and human pluripotent stem cells
Shicheng Sun1,2,3, Kevin Wijanarko1,2,3, Oniko Liani1,2,3
1Murdoch Children's Research Institute, The Royal Children's Hospital, Parkville, Victoria, Australia.
Immunological Reviews
|March 20, 2023
Summary
During early development, lymphoid cells originate from progenitors before hematopoietic stem cells (HSCs). Pluripotent stem cell models show these cells can be generated independently of HSCs, offering new clinical avenues.
Area of Science:
- Immunology
- Developmental Biology
- Stem Cell Biology
Background:
- Lymphoid cells, including T, B, Natural Killer T (NKT), and Innate Lymphoid Cells (ILCs) like Natural Killer (NK) cells, are crucial for adaptive and innate immunity.
- Traditionally, adult lymphoid cell development is attributed to long-term hematopoietic stem cells (HSCs) in the bone marrow.
- However, embryonic and fetal lymphoid cell origins are complex, with evidence suggesting derivation from earlier progenitor populations preceding HSC emergence.
Purpose of the Study:
- To investigate the ontogeny of lymphoid cells originating from non-HSC progenitor populations during embryogenesis.
- To review technological advancements in differentiating human lymphoid cells from pluripotent stem cells.
- To explore the clinical translation potential of these findings for generating lymphoid immune cells.
Main Methods:
- Utilizing single-cell RNA-sequencing technologies to analyze lymphoid cell development.
- Employing pluripotent stem cell (PSC)-based developmental models to generate lymphoid cells in vitro.
- Examining hematopoiesis in vivo during embryonic and fetal development.
Main Results:
- Pluripotent stem cell differentiation platforms have successfully generated lymphoid immune cells independently of HSCs.
- These findings support in vivo observations of lymphoid cell origins from non-HSC progenitors during embryogenesis.
- New insights into the complex and multifaceted ontogeny of lymphoid cells have been revealed.
Conclusions:
- Lymphoid cell development during embryogenesis arises from progenitor populations that predate HSCs.
- Pluripotent stem cell differentiation offers a viable method for generating lymphoid cells independent of HSCs.
- Advances in PSC differentiation hold promise for clinical applications in regenerative medicine and immunotherapy.
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