Hematopoietic stem cells (HSCs)—with their self-renewal and multi-lineage differentiation potential—are top of the hematopoietic cell hierarchy. Stress conditions activate the quiescent HSCs, which in turn enter cel...Hematopoietic stem cells (HSCs)—with their self-renewal and multi-lineage differentiation potential—are top of the hematopoietic cell hierarchy. Stress conditions activate the quiescent HSCs, which in turn enter cell cycle to produce their progenies (Sawai et al., 2016).展开更多
Radioprotection was previously considered as a function of hematopoietic stem cells(HSCs).However,recent studies have reported its activity in hematopoietic progenitor cells(HPCs).To address this issue,we compared the...Radioprotection was previously considered as a function of hematopoietic stem cells(HSCs).However,recent studies have reported its activity in hematopoietic progenitor cells(HPCs).To address this issue,we compared the radioprotection activity in 2 subsets of HSCs(nHSC1 and 2 populations)and 4 subsets of HPCs(nHPC1–4 populations)of the mouse bone marrow,in relation to their in vitro and in vivo colony-forming activity.Significant radioprotection activity was detected in the nHSC2 population enriched in lymphoid-biased HSCs.Moderate radioprotection activity was detected in nHPC1 and 2 populations enriched in myeloid-biased HPCs.Low radioprotection activity was detected in the nHSC1 enriched in myeloid-biased HSCs.No radioprotection activity was detected in the nHPC3 and 4 populations that included MPP4(LMPP).Single-cell colony assay combined with flow cytometry analysis showed that the nHSC1,nHSC2,nHPC1,and nHPC2 populations had the neutrophils/macrophages/erythroblasts/megakaryocytes(nmEMk)differentiation potential whereas the nHPC3 and 4 populations had only the nm differentiation potential.Varying day 12 spleen colony-forming units(day 12 CFU-S)were detected in the nHSC1,nHSC2,and nHPC1–3 populations,but very few in the nHPC4 population.These data suggested that nmEMk differentiation potential and day 12 CFU-S activity are partially associated with radioprotection activity.Reconstitution analysis showed that sufficient myeloid reconstitution around 12 to 14 days after transplantation was critical for radioprotection.This study implied that radioprotection is specific to neither HSC nor HPC populations,and that lymphoid-biased HSCs and myeloid-biased HPCs as populations play a major role in radioprotection.展开更多
Ex vivo expansion of hematopoietic stem cells(HSCs)is considered the holy grail in stem cell biology and therapy,as it has long been difficult to make this procedure possible.Yamazaki’s research team has established ...Ex vivo expansion of hematopoietic stem cells(HSCs)is considered the holy grail in stem cell biology and therapy,as it has long been difficult to make this procedure possible.Yamazaki’s research team has established new,polyvinyl alcohol-based culture conditions and shown a significant expansion of mouse HSCs from a small number of cells after a month of culture.Surprisingly,expanded HSCs were able to reconstitute unconditioned normal mice.There is generally a technical concern in limiting dilution assay to estimate a fold-expansion of HSCs.But,this work paves the way toward expansion of human HSCs useful for transplantation medicine.展开更多
Hematopoietic stem cells(HSCs)self-renew or differentiate through division.Cytokines are essential for inducing HSC division,but the optimal cytokine combination to control self-renewal of HSC in vitro remains unclear...Hematopoietic stem cells(HSCs)self-renew or differentiate through division.Cytokines are essential for inducing HSC division,but the optimal cytokine combination to control self-renewal of HSC in vitro remains unclear.In this study,we compared the effects of interleukin-12(IL-12)and thrombopoietin(TPO)in combination with stem cell factor(SCF)on in vitro self-renewal of HSCs.Single-cell assays were used to overcome the heterogeneity issue of HSCs,and serum-free conditions were newly established to permit reproduction of data.In single-cell cultures,CD150^(+)CD48^(-)CD41^(-)CD34^(-)c-Kit^(+)Sca-1^(+)lineage^(-)SCs divided significantly more slowly in the presence of SCF+IL-12 compared with cells in the presence of SCF+TPO.Serial transplantation of cells from bulk and clonal cultures revealed that TPO was more effective than IL-12 at supporting in vitro self-renewal of short-term(<6 months)HSCs,resulting in a monophasic reconstitution wave formation,whereas IL-12 was more effective than TPO at supporting the in vitro selfrenewal of long-term(>6 months)HSCs,resulting in a biphasic reconstitution wave formation.The control of division rate in HSCs appeared to be crucial for preventing the loss of self-renewal potential from their in vitro culture.展开更多
基金supported by the grants from the National Key R&D Program of China (2016YFA0100600, 2017YFA0103400, 2017YFA0104900)the National Natural Science Foundation of China (81421002, 81922002)+1 种基金CAMS Initiative for Innovative Medicine 2017-I2M-1-015, 2017-I2M-3-009, 2016-I2M-1-017, and 2019-I2M-1-006the Atlas of Blood Cell Alliance。
文摘Hematopoietic stem cells (HSCs)—with their self-renewal and multi-lineage differentiation potential—are top of the hematopoietic cell hierarchy. Stress conditions activate the quiescent HSCs, which in turn enter cell cycle to produce their progenies (Sawai et al., 2016).
基金the National Key Rescarch and Development Program of China Stem Cell and Translational Research(2017YFA0104900,2016YFA0100600,and 2019YFA0110203)CAMS Initiative for Innovative Medi-cine(CAMS-12M)(2016-I2M-1-017 and 2017-I2M-1-015)+1 种基金CAMS Fundamental Rescarch Funds for Central RescarchInstitutes(2019PT320017)the National Natural ScienceFoundation of China(81670105,81970119,and 81421002).
文摘Radioprotection was previously considered as a function of hematopoietic stem cells(HSCs).However,recent studies have reported its activity in hematopoietic progenitor cells(HPCs).To address this issue,we compared the radioprotection activity in 2 subsets of HSCs(nHSC1 and 2 populations)and 4 subsets of HPCs(nHPC1–4 populations)of the mouse bone marrow,in relation to their in vitro and in vivo colony-forming activity.Significant radioprotection activity was detected in the nHSC2 population enriched in lymphoid-biased HSCs.Moderate radioprotection activity was detected in nHPC1 and 2 populations enriched in myeloid-biased HPCs.Low radioprotection activity was detected in the nHSC1 enriched in myeloid-biased HSCs.No radioprotection activity was detected in the nHPC3 and 4 populations that included MPP4(LMPP).Single-cell colony assay combined with flow cytometry analysis showed that the nHSC1,nHSC2,nHPC1,and nHPC2 populations had the neutrophils/macrophages/erythroblasts/megakaryocytes(nmEMk)differentiation potential whereas the nHPC3 and 4 populations had only the nm differentiation potential.Varying day 12 spleen colony-forming units(day 12 CFU-S)were detected in the nHSC1,nHSC2,and nHPC1–3 populations,but very few in the nHPC4 population.These data suggested that nmEMk differentiation potential and day 12 CFU-S activity are partially associated with radioprotection activity.Reconstitution analysis showed that sufficient myeloid reconstitution around 12 to 14 days after transplantation was critical for radioprotection.This study implied that radioprotection is specific to neither HSC nor HPC populations,and that lymphoid-biased HSCs and myeloid-biased HPCs as populations play a major role in radioprotection.
文摘Ex vivo expansion of hematopoietic stem cells(HSCs)is considered the holy grail in stem cell biology and therapy,as it has long been difficult to make this procedure possible.Yamazaki’s research team has established new,polyvinyl alcohol-based culture conditions and shown a significant expansion of mouse HSCs from a small number of cells after a month of culture.Surprisingly,expanded HSCs were able to reconstitute unconditioned normal mice.There is generally a technical concern in limiting dilution assay to estimate a fold-expansion of HSCs.But,this work paves the way toward expansion of human HSCs useful for transplantation medicine.
基金supported by grants from the National Key Research and Development Program of China Stem Cell and Translational Research(2017YFA0104903,2016YFA0100600,and 2017YFA0103400)the Ministry of Science and Technology of China(2015CB964403 and,2011CB964801)+1 种基金the CAMS Initiative for Innovative Medicine(2016-I2M-1-017 and 2017-I2M-1-015)the National Natural Science Foundation of China(81470279,81670105,81421002,81400077,and 81500085).
文摘Hematopoietic stem cells(HSCs)self-renew or differentiate through division.Cytokines are essential for inducing HSC division,but the optimal cytokine combination to control self-renewal of HSC in vitro remains unclear.In this study,we compared the effects of interleukin-12(IL-12)and thrombopoietin(TPO)in combination with stem cell factor(SCF)on in vitro self-renewal of HSCs.Single-cell assays were used to overcome the heterogeneity issue of HSCs,and serum-free conditions were newly established to permit reproduction of data.In single-cell cultures,CD150^(+)CD48^(-)CD41^(-)CD34^(-)c-Kit^(+)Sca-1^(+)lineage^(-)SCs divided significantly more slowly in the presence of SCF+IL-12 compared with cells in the presence of SCF+TPO.Serial transplantation of cells from bulk and clonal cultures revealed that TPO was more effective than IL-12 at supporting in vitro self-renewal of short-term(<6 months)HSCs,resulting in a monophasic reconstitution wave formation,whereas IL-12 was more effective than TPO at supporting the in vitro selfrenewal of long-term(>6 months)HSCs,resulting in a biphasic reconstitution wave formation.The control of division rate in HSCs appeared to be crucial for preventing the loss of self-renewal potential from their in vitro culture.
