title: Induced Pluripotent Stem Cells Can Effectively Differentiate into Multiple Functional Lymphocyte Lineages In Vivo with Negligible Bias.
abstract: Lymphohematopoietic stem cells (L-HSCs) generated from self-somatic cell-derived induced pluripotent stem cells (iPSCs) are a potential source of cells for the treatment of hematological disorders. However, the generation of truly functional L-HSCs from iPSCs has yet to be achieved. Thus, whether iPSCs have the inherent potential to generate a normal differentiated phenotype and functional population of multiple lineages of terminally differentiated lymphocytes needs to be assessed. Here, we used tetraploid embryo complementation to provide a normal environment for the differentiation of hematopoietic cells from iPSCs and embryonic stem cells (ESCs). We then evaluated the characteristics, populations, and functions of lymphocytes derived from iPSCs, ESCs, and naïve isogenic C57BL/6 mice. The results showed that iPSC-derived lymphocytes (iPSLs) expressed normal levels of major histocompatibility complex-I (MHC-I) and exhibited a fully pluripotent capacity to differentiate into CD4(+) T, CD8(+) T, regulatory T, B, and natural killer cells. Following in vitro stimulation with either concanavalin A or an alloantigen, iPSLs exhibited the same capacities for proliferation and cytokine secretion as ESC-derived or isogenic lymphocytes. Furthermore, iPSC-derived bone marrow cells could differentiate into multiple lymphocyte lineages that reconstituted the lymphocyte population in syngeneic lethally irradiated recipient animals. Our results demonstrated that iPSCs have the inherent potential to differentiate into multiple lineages of functional lymphocytes without bias, and further support the practical application of iPSC-based treatments to hematological disorders.
authors.affiliation: 1 Organ Transplantation Institute, Medical College of Xiamen University , Xiamen, Fujian, China .
authors.forename: Tianshu
authors.initials: T
authors.lastname: Lan
authors.affiliation: 2 State Key Laboratory of Reproductive Biology, Institute of Zoology , Chinese Academy of Sciences, Beijing, China .|3 Graduate University of the Chinese Academy of Sciences , Beijing, China .
authors.forename: Libin
authors.initials: L
authors.lastname: Wang
authors.affiliation: 1 Organ Transplantation Institute, Medical College of Xiamen University , Xiamen, Fujian, China .
authors.forename: Lin
authors.initials: L
authors.lastname: Xu
authors.affiliation: 1 Organ Transplantation Institute, Medical College of Xiamen University , Xiamen, Fujian, China .
authors.forename: Ning
authors.initials: N
authors.lastname: Jin
authors.affiliation: 1 Organ Transplantation Institute, Medical College of Xiamen University , Xiamen, Fujian, China .
authors.forename: Guoliang
authors.initials: G
authors.lastname: Yan
authors.affiliation: 1 Organ Transplantation Institute, Medical College of Xiamen University , Xiamen, Fujian, China .
authors.forename: Junjie
authors.initials: J
authors.lastname: Xia
authors.affiliation: 1 Organ Transplantation Institute, Medical College of Xiamen University , Xiamen, Fujian, China .
authors.forename: Hailong
authors.initials: H
authors.lastname: Wang
authors.affiliation: 1 Organ Transplantation Institute, Medical College of Xiamen University , Xiamen, Fujian, China .
authors.forename: Guohong
authors.initials: G
authors.lastname: Zhuang
authors.affiliation: 1 Organ Transplantation Institute, Medical College of Xiamen University , Xiamen, Fujian, China .
authors.forename: Chang
authors.initials: C
authors.lastname: Gao
authors.affiliation: 4 The First Affiliated Hospital of Xiamen University , Xiamen, Fujian, China .
authors.forename: Luxi
authors.initials: L
authors.lastname: Meng
authors.affiliation: 1 Organ Transplantation Institute, Medical College of Xiamen University , Xiamen, Fujian, China .
authors.forename: Feifei
authors.initials: F
authors.lastname: Du
authors.affiliation: 2 State Key Laboratory of Reproductive Biology, Institute of Zoology , Chinese Academy of Sciences, Beijing, China .
authors.forename: Qi
authors.initials: Q
authors.lastname: Zhou
authors.affiliation: 1 Organ Transplantation Institute, Medical College of Xiamen University , Xiamen, Fujian, China .
authors.forename: Zhongquan
authors.initials: Z
authors.lastname: Qi
mesh_terms: D000818:Animals; D019070:Cell Lineage; D002478:Cells, Cultured; D053595:Embryonic Stem Cells / Q000166:cytology; D057026:Induced Pluripotent Stem Cells / Q000166:cytology*; D008214:Lymphocytes / Q000166:cytology*; D038041:Lymphopoiesis; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL