Generation of CD34 + CD43 + hematopoietic progenitors to induce thymocytes from human pluripotent stem cells
| Autor: | Anne Gaignerie, Xavier Saulquin, Céline Sérazin, Laurent David, Carole Guillonneau, Olivier Baron, Ignacio Anegon, Léa Flippe |
|---|---|
| Přispěvatelé: | Centre de Recherche en Transplantation et Immunologie (U1064 Inserm - CRTI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Centre hospitalier universitaire de Nantes (CHU Nantes), Structure fédérative de recherche François Bonamy (SFR François Bonamy), Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche en Santé de l'Université de Nantes (IRS-UN), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), guillonneau, carole, Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes) |
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
hiPSC
hESC hematopoietic progenitor T-cell progenitor hematopoietic differentiation 0303 health sciences [SDV.IMM] Life Sciences [q-bio]/Immunology CD34 General Medicine Biology Embryonic stem cell 3. Good health Cell biology 03 medical and health sciences Haematopoiesis 0302 clinical medicine Cord blood [SDV.IMM]Life Sciences [q-bio]/Immunology Lymphopoiesis Stem cell Progenitor cell Induced pluripotent stem cell 030304 developmental biology 030215 immunology |
| Zdroj: | Cells; Volume 11; Issue 24; Pages: 4046 |
| Popis: | Immunotherapy using primary T cells has revolutionized medical care in some pathologies in recent years, but limitations associated to challenging cell genome edition, insufficient cell number production, the use of only autologous cells, and the lack of product standardization have limited its clinical use. The alternative use of T cells generated in vitro from human pluripotent stem cells (hPSCs) offers great advantages by providing a self-renewing source of T cells that can be readily genetically modified and facilitate the use of standardized universal off-the-shelf allogeneic cell products and rapid clinical access. However, despite their potential, a better understanding of the feasibility and functionality of T cells differentiated from hPSCs is necessary before moving into clinical settings. In this study, we generated human-induced pluripotent stem cells from T cells (T-iPSCs), allowing for the preservation of already recombined TCR, with the same properties as human embryonic stem cells (hESCs). Based on these cells, we differentiated, with high efficiency, hematopoietic progenitor stem cells (HPSCs) capable of self-renewal and differentiation into any cell blood type, in addition to DN3a thymic progenitors from several T-iPSC lines. In order to better comprehend the differentiation, we analyzed the transcriptomic profiles of the different cell types and demonstrated that HPSCs differentiated from hiPSCs had very similar profiles to cord blood hematopoietic stem cells (HSCs). Furthermore, differentiated T-cell progenitors had a similar profile to thymocytes at the DN3a stage of thymic lymphopoiesis. Therefore, utilizing this approach, we were able to regenerate precursors of therapeutic human T cells in order to potentially treat a wide range of diseases. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|