Single-cell mapping of progressive fetal-to-adult transition in human naïve T cells
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ABSTRACT:
PROVIDER: PRJNA665464 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Whereas the human fetal immune system is poised to generate immune tolerance and suppress inflammation in utero, an adult-like immune system emerges to orchestrate anti-pathogen immune responses in post-natal life. It has been posited that cells of the adult immune system arise as a discrete ontological “layer” of hematopoietic stem-progenitor cells (HSPCs) and their progeny; evidence supporting this model in humans has, however, been inconclusive. Here, we combine bulk and single-cell transcriptional profiling of lymphoid, myeloid, and HSPCs from fetal, perinatal, and adult developmental stages to demonstrate that the fetal-to-adult transition occurs progressively along a continuum of maturity—with a substantial degree of interindividual variation at the time of birth—rather than via a transition between discrete waves. These findings have important implications in the design of strategies for prophylaxis against infection in the newborn, and for the use of umbilical cord blood (UCB) in the setting of transplantation. Naïve CD4 and CD8 T cells, and CD34+ hematopoietic stem and progenitor cells (HSPCs) were isolated from human samples of three different groups: Fetal (18-23 gestational weeks), full-term newborn (37+ gestational weeks at birth), and adults age 23 to 53. For each group, five independent donors were analyzed, but not all cell types could be sequenced for every patient.
2020-09-25 | GSE158491 | GEO
Project description:Whereas the human fetal immune system is poised to generate immune tolerance and suppress inflammation in utero, an adult-like immune system emerges to orchestrate anti-pathogen immune responses in post-natal life. It has been posited that cells of the adult immune system arise as a discrete ontological “layer” of hematopoietic stem-progenitor cells (HSPCs) and their progeny; evidence supporting this model in humans has, however, been inconclusive. Here, we combine bulk and single-cell transcriptional profiling of lymphoid, myeloid, and HSPCs from fetal, perinatal, and adult developmental stages to demonstrate that the fetal-to-adult transition occurs progressively along a continuum of maturity—with a substantial degree of interindividual variation at the time of birth—rather than via a transition between discrete waves. These findings have important implications in the design of strategies for prophylaxis against infection in the newborn, and for the use of umbilical cord blood (UCB) in the setting of transplantation. Naïve CD4 and CD8 T cells, and CD34+ hematopoietic stem and progenitor cells (HSPCs) were isolated from human samples of three different groups: Fetal (18-23 gestational weeks), full-term newborn (37+ gestational weeks at birth), and adults age 23 to 53. For each group, five independent donors were analyzed, but not all cell types could be sequenced for every patient.
2020-09-25 | GSE158490 | GEO
Project description:Whereas the human fetal immune system is poised to generate immune tolerance and suppress inflammation in utero, an adult-like immune system emerges to orchestrate anti-pathogen immune responses in post-natal life. It has been posited that cells of the adult immune system arise as a discrete ontological “layer” of hematopoietic stem-progenitor cells (HSPCs) and their progeny; evidence supporting this model in humans has, however, been inconclusive. Here, we combine bulk and single-cell transcriptional profiling of lymphoid, myeloid, and HSPCs from fetal, perinatal, and adult developmental stages to demonstrate that the fetal-to-adult transition occurs progressively along a continuum of maturity—with a substantial degree of interindividual variation at the time of birth—rather than via a transition between discrete waves. These findings have important implications in the design of strategies for prophylaxis against infection in the newborn, and for the use of umbilical cord blood (UCB) in the setting of transplantation. Naïve CD4 and CD8 T cells, and CD34+ hematopoietic stem and progenitor cells (HSPCs) were isolated from human samples of three different groups: Fetal (18-23 gestational weeks), full-term newborn (37+ gestational weeks at birth), and adults age 23 to 53. For each group, five independent donors were analyzed, but not all cell types could be sequenced for every patient.
2020-09-25 | GSE158492 | GEO
Project description:Single-cell mapping of progressive fetal-to-adult transition in human hematopoiesis. [CD4 - bulk RNAseq]
| PRJNA665473 | ENA
Project description:Single-cell mapping of progressive fetal-to-adult transition in human hematopoiesis [HSPCs single-cell RNAseq]
| PRJNA665467 | ENA
Project description:Single-cell mapping of progressive fetal-to-adult transition in human hematopoiesis. [CD4 & CD8 single-cell RNAseq]
| PRJNA665472 | ENA
Project description:We compared differences in fetal and adult T cells by performing whole genome profiling on sort-purified T cells (naïve CD4+ and Treg cells) from human fetal specimens (18-22 gestational weeks) and adult specimens (age 25-40 years old). Fetal and Adult Naïve CD4+ T cells phenotype: CD3+CD4+CD45RA+CCR7+CD27+, Fetal and Adult CD4+CD25+ Treg phenotype: CD3+CD4+CD25bright Four different groups were analyzed: Fetal Naïve CD4+ T cells, Adult Naïve CD4+ T cells, Fetal Treg cells, Adult Treg cells. For each group three independent donors were analyzed.
2010-12-17 | E-GEOD-25087 | biostudies-arrayexpress
Project description:This SuperSeries is composed of the SubSeries listed below.
2020-09-25 | GSE158493 | GEO
Project description:We compared differences in fetal and adult T cells by performing whole genome profiling on sort-purified T cells (naïve CD4+ and Treg cells) from human fetal specimens (18-22 gestational weeks) and adult specimens (age 25-40 years old). Fetal and Adult Naïve CD4+ T cells phenotype: CD3+CD4+CD45RA+CCR7+CD27+, Fetal and Adult CD4+CD25+ Treg phenotype: CD3+CD4+CD25bright
2010-12-17 | GSE25087 | GEO
Project description:Limb development has long served as a model system for studying how a pool of progenitor cells undergoes coordinated spatial patterning and differentiation to produce complex and well-organized structures. Here, we identify a population of naïve-state limb progenitors and show that they differentiate progressively to form the skeleton in a complex nonconsecutive three-dimensional pattern. First, by performing single-cell RNA sequencing of the developing mouse forelimb we created an atlas of cellular compositions and transcriptional states. This atlas revealed three progenitor states: naïve, proximal and autopodial, as well as Msx1 as a marker for the naïve progenitors. In vivo lineage tracing analysis firmly established this role of Msx1 and localized the naïve progenitors to the outer margin of the developing limb, along the anterior-posterior axis. Sequential pulse-chase experiments showed that Msx1 naïve progenitors undergo progressive and simultaneous transition into both proximal and autopodial progenitors and then to Sox9+ chondroprogenitors. Interestingly, the progressive differentiation to chondroprogenitors occurred along all the skeletal segments concurrently, suggesting that skeleton form in a nonconsecutive way. Indeed, by tracking the spatiotemporal sequence of naïve progenitor differentiation, we found that the skeleton forms in a complex nonconsecutive three-dimensional pattern. Overall, these findings propose a new model for limb skeleton development. Limb development has long served as a model system for studying how a pool of progenitor cells undergoes coordinated spatial patterning and differentiation to produce complex and well-organized structures. Here, we identify a population of naïve-state limb progenitors and show that they differentiate progressively to form the skeleton in a complex nonconsecutive three-dimensional pattern. First, by performing single-cell RNA sequencing of the developing mouse forelimb we created an atlas of cellular compositions and transcriptional states. This atlas revealed three progenitor states: naïve, proximal and autopodial, as well as Msx1 as a marker for the naïve progenitors. In vivo lineage tracing analysis firmly established this role of Msx1 and localized the naïve progenitors to the outer margin of the developing limb, along the anterior-posterior axis. Sequential pulse-chase experiments showed that Msx1 naïve progenitors undergo progressive and simultaneous transition into both proximal and autopodial progenitors and then to Sox9+ chondroprogenitors. Interestingly, the progressive differentiation to chondroprogenitors occurred along all the skeletal segments concurrently, suggesting that skeleton form in a nonconsecutive way. Indeed, by tracking the spatiotemporal sequence of naïve progenitor differentiation, we found that the skeleton forms in a complex nonconsecutive three-dimensional pattern. Overall, these findings propose a new model for limb skeleton development. Limb development has long served as a model system for studying how a pool of progenitor cells undergoes coordinated spatial patterning and differentiation to produce complex and well-organized structures. Here, we identify a population of naïve-state limb progenitors and show that they differentiate progressively to form the skeleton in a complex nonconsecutive three-dimensional pattern. First, by performing single-cell RNA sequencing of the developing mouse forelimb we created an atlas of cellular compositions and transcriptional states. This atlas revealed three progenitor states: naïve, proximal and autopodial, as well as Msx1 as a marker for the naïve progenitors. In vivo lineage tracing analysis firmly established this role of Msx1 and localized the naïve progenitors to the outer margin of the developing limb, along the anterior-posterior axis. Sequential pulse-chase experiments showed that Msx1 naïve progenitors undergo progressive and simultaneous transition into both proximal and autopodial progenitors and then to Sox9+ chondroprogenitors. Interestingly, the progressive differentiation to chondroprogenitors occurred along all the skeletal segments concurrently, suggesting that skeleton form in a nonconsecutive way. Indeed, by tracking the spatiotemporal sequence of naïve progenitor differentiation, we found that the skeleton forms in a complex nonconsecutive three-dimensional pattern. Overall, these findings propose a new model for limb skeleton development.
2023-01-17 | GSE185940 | GEO