Dear Editor,In recent years,there is growing interest regarding the roles of senescent bone marrow(BM)microenvironment in the initiation of leukemia.Aged mice transplanted with AML1-ETO(AML1-ETO fusion protein)-positi...Dear Editor,In recent years,there is growing interest regarding the roles of senescent bone marrow(BM)microenvironment in the initiation of leukemia.Aged mice transplanted with AML1-ETO(AML1-ETO fusion protein)-positive hematopoietic stem cells(HSCs)present with a significant increase in the frequency of AMLETO-positive early progenitor cells in BM as well as an in crease of immature myeloid cells compared to young recipients(Vas et aL,2012).BM mesenchymal stem cells(MSCs)from myelodysplastic syndromes(MDS)animal models and MDS patients exhibit impaired proliferation and differentiation potentials,abnormal cytoki ne secretion,and dysregulated gene expression profile(Lopez-Villar et al.,2009;Geyh et al.,2013;Mattiucci et al.,2018).However,the causal relationship between senes・cent BM microenvironment and leukemia development is unclear.Whether senes・cent BM microenvironment initiates or accelerates leukemia development remains unknown.展开更多
Chimeric antigen receptor T cell(CAR-T)therapy is one of the most promising approaches in cancer treatment.1 However,the limited availability of patient-derived T cells narrows its universal applicability.Thus,it is n...Chimeric antigen receptor T cell(CAR-T)therapy is one of the most promising approaches in cancer treatment.1 However,the limited availability of patient-derived T cells narrows its universal applicability.Thus,it is necessary to invent new methods to obtain alternative T-cell sources.Pluripotent stem cells(PSCs),which have unlimited culture potential and are amenable to gene editing,are ideal for generating induced T(iT)cells.展开更多
Numerous efforts have been attempted to regenerate T cells in culture dish from pluripotent stem cells(PSCs).However,in vitro generated T cells exhibited extremely low activity and compromised immunocompetency in vivo...Numerous efforts have been attempted to regenerate T cells in culture dish from pluripotent stem cells(PSCs).However,in vitro generated T cells exhibited extremely low activity and compromised immunocompetency in vivo.Here,we describe a two-step protocol for regenerating functional T cells using an inducible Runx1-Hoxa9-PSC(iR9-PSCs)line.The procedure mainly includes generation of induced hematopoietic progenitor cells(iHPCs)in vitro,transplantation,and development of functional induced T cells(iT)in vivo via transplantation.The entire induction process in vitro requires 21 days before iHPCs transplantation.The development of mature T cells in vivo takes 4 to 6 weeks post-transplantation.We provide a simple and reproducible approach for functional T cell regeneration from iR9-PSCs for research purpose.展开更多
基金Supplementary material is available at Journal of Molecular Cell Biology online.This work was supported by grants from the National Natural Science Foundation of Chino(81925002,81970099,and 31900814)the Strategic Priority Research Program of Chinese Academy of Sciences(XDA16010601)+3 种基金the Key Research Development Program of Bioland Laboratory(Guangzhou Regenerative Medicine and Health Guangdong Laboratory)(2018GZR110104006)the Science and Technology Planning Project of Guangdong Province(2017BO 30314056 and 2017B020230004)the CAS Key Research Program of Frontier Sciences(QYZDB.SSW.SMC057)the Health and Medical Core Collaborative Innovation Program of Guangzhou Scientific and Technology(201803040017).
文摘Dear Editor,In recent years,there is growing interest regarding the roles of senescent bone marrow(BM)microenvironment in the initiation of leukemia.Aged mice transplanted with AML1-ETO(AML1-ETO fusion protein)-positive hematopoietic stem cells(HSCs)present with a significant increase in the frequency of AMLETO-positive early progenitor cells in BM as well as an in crease of immature myeloid cells compared to young recipients(Vas et aL,2012).BM mesenchymal stem cells(MSCs)from myelodysplastic syndromes(MDS)animal models and MDS patients exhibit impaired proliferation and differentiation potentials,abnormal cytoki ne secretion,and dysregulated gene expression profile(Lopez-Villar et al.,2009;Geyh et al.,2013;Mattiucci et al.,2018).However,the causal relationship between senes・cent BM microenvironment and leukemia development is unclear.Whether senes・cent BM microenvironment initiates or accelerates leukemia development remains unknown.
基金supported by the CAS Key Research Program of Frontier Sciences(QYZDB-SSW-SMC057)the Strategic Priority Research Program of Chinese Academy of Sciences(XDA16010601)+4 种基金the National Key R&D Program of China(2019YFA0110203)the Major Research and Development Project of Guangzhou Regenerative Medicine and Health Guangdong Laboratory(2018GZR110104006)the Health and Medical Care Collaborative Innovation Program of Guangzhou Scientific and Technology(201803040017)the Science and Technology Planning Project of Guangdong Province(2017B030314056)the National Natural Science Foundation of China(81925002,81970099,31900814).
文摘Chimeric antigen receptor T cell(CAR-T)therapy is one of the most promising approaches in cancer treatment.1 However,the limited availability of patient-derived T cells narrows its universal applicability.Thus,it is necessary to invent new methods to obtain alternative T-cell sources.Pluripotent stem cells(PSCs),which have unlimited culture potential and are amenable to gene editing,are ideal for generating induced T(iT)cells.
基金This work was supported by grants from the Strategic Priority Research Program of Chinese Academy of Sciences(XDA16010601)the Health and Medical Care Collaborative Innovation Program of Guangzhou Scientific and Technology(201803040017)+4 种基金the CAS Key Research Program of Frontier Sciences(QYZDB-SSW-SMC057)the National Key R&D Program of China(2019YFA0110200)the Major Research and Development Project of Guangzhou Regenerative Medicine and Health Guangdong Laboratory(2018GZR110104006)the Science and Technology Planning Project of Guangdong Province(2017B030314056)the grants from the National Natural Science Foundation of China(Grant No 81925002).
文摘Numerous efforts have been attempted to regenerate T cells in culture dish from pluripotent stem cells(PSCs).However,in vitro generated T cells exhibited extremely low activity and compromised immunocompetency in vivo.Here,we describe a two-step protocol for regenerating functional T cells using an inducible Runx1-Hoxa9-PSC(iR9-PSCs)line.The procedure mainly includes generation of induced hematopoietic progenitor cells(iHPCs)in vitro,transplantation,and development of functional induced T cells(iT)in vivo via transplantation.The entire induction process in vitro requires 21 days before iHPCs transplantation.The development of mature T cells in vivo takes 4 to 6 weeks post-transplantation.We provide a simple and reproducible approach for functional T cell regeneration from iR9-PSCs for research purpose.
