Transcriptomic profiling of 27-year cryopreserved umbilical cord blood HSCs/HPCs
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE225699 | GEO | 2023/10/04
REPOSITORIES: GEO
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Project description:Human umbilical cord blood cells (UCB) is an important alternative resource for the hematopoietic stem cells in treatment of leukemia and other non-malignant diseases. The failure of hematopoiesis reconstruction by the UCB is known to be associated with several clinicopathological features of host patients. There are very few reports available, however, seeking for the association with the quality of umbilical cord blood cells (UCB) themselves. Here we try to address the quality of UCBs by transfusion to the lethally irradiated immunocompromized mice. The cryopreserved CD34+ UCBs cells from twelve different single human donors were transplanted to the irradiated NOD/shi-scid Jic mice. In parallel, total RNAs of the UCBs were subjected to the gene expression profiling with oligonucleotide microarrays. The UCBs from three donors failed to establish the engraftment in the host mice whereas other 9 UCBs succeeded to various extents. Oligonucleotide microarray analysis indicated that 71 genes, including HOXB4 and ETS2, were specifically overexpressed and 23 genes were suppressed more than 2 fold in the successful UCBs comparing with the failed ones (p<0.005, Student’s t-test). Functional annotation analyses revealed that the genes mediated cell growth and cell cycle regulations were enriched in successful UCBs comparing with the failed ones. Our results suggest that the hematopoiesis reconstitution ability may vary among the cryopreserved UCBs and the quality can be distinguished with certain sets of gene expression. The gene expression in human umbilical cord blood cells (UCBs) was measured before transplantation to the lethally irradiated immunocompromized mice. UCBs from 12 individuals were examined.
2010-07-15 | E-GEOD-19835 | biostudies-arrayexpress
Project description:Transplantation with low numbers of hematopoietic stem cells (HSCs), found in many of the publically accessible cryopreserved umbilical cord blood (UCB) units, leads to delayed time to engraftment, high graft failure rates, and early mortality in many patients. A chemical screen in zebrafish identified the prostaglandin compound, 16,16 dimethyl prostaglandin E2 (dmPGE2), to be a critical regulator of hematopoietic stem cell homeostasis. We hypothesized that an ex vivo modulation with dmPGE2 prior to transplantation would lead to enhanced engraftment by increasing the “effective” dose of hematopoietic stem cells (HSCs) in cord blood. A phase I trial of reduced-intensity double UCB transplantation was performed to evaluate safety, rates of engraftment and fractional chimerism of dmPGE2 enhanced UCB units. To explore potential causes of the lack of enhanced efficacy in the first cohort, we characterized HSCs to determine whether the prostaglandin pathway was being activated under the ex vivo incubation conditions (4°C, 10µM dmPGE2, 60 minutes). Incubation conditions were identified (37°C, 10µM dmPGE2, 120 minutes) that maximize the activation of the prostaglandin pathway by dmPGE2 in human CD34+ cells. Isolated human CD34+ from umbilical cord blood were incubated ex vivo in Stem Span media with 10uM 16,16-dmPGE2 or DMSO. Two treatment conditions were evaluated (4 deg C for 1 hour, 37 deg C for 2 hours) with either 3 or 7 biological replicates at each condition. Total RNA was isolated post incubation and analyzed on Affymetrix microarrays for pathway activation.
2012-04-15 | E-GEOD-36547 | biostudies-arrayexpress
Project description:Transplantation with low numbers of hematopoietic stem cells (HSCs), found in many of the publically accessible cryopreserved umbilical cord blood (UCB) units, leads to delayed time to engraftment, high graft failure rates, and early mortality in many patients. A chemical screen in zebrafish identified the prostaglandin compound, 16,16 dimethyl prostaglandin E2 (dmPGE2), to be a critical regulator of hematopoietic stem cell homeostasis. We hypothesized that an ex vivo modulation with dmPGE2 prior to transplantation would lead to enhanced engraftment by increasing the “effective” dose of hematopoietic stem cells (HSCs) in cord blood. A phase I trial of reduced-intensity double UCB transplantation was performed to evaluate safety, rates of engraftment and fractional chimerism of dmPGE2 enhanced UCB units. To explore potential causes of the lack of enhanced efficacy in the first cohort, we characterized HSCs to determine whether the prostaglandin pathway was being activated under the ex vivo incubation conditions (4°C, 10µM dmPGE2, 60 minutes). Incubation conditions were identified (37°C, 10µM dmPGE2, 120 minutes) that maximize the activation of the prostaglandin pathway by dmPGE2 in human CD34+ cells.
2012-04-16 | GSE36547 | GEO
Project description:Human umbilical cord blood cells (UCB) is an important alternative resource for the hematopoietic stem cells in treatment of leukemia and other non-malignant diseases. The failure of hematopoiesis reconstruction by the UCB is known to be associated with several clinicopathological features of host patients. There are very few reports available, however, seeking for the association with the quality of umbilical cord blood cells (UCB) themselves. Here we try to address the quality of UCBs by transfusion to the lethally irradiated immunocompromized mice. The cryopreserved CD34+ UCBs cells from twelve different single human donors were transplanted to the irradiated NOD/shi-scid Jic mice. In parallel, total RNAs of the UCBs were subjected to the gene expression profiling with oligonucleotide microarrays. The UCBs from three donors failed to establish the engraftment in the host mice whereas other 9 UCBs succeeded to various extents. Oligonucleotide microarray analysis indicated that 71 genes, including HOXB4 and ETS2, were specifically overexpressed and 23 genes were suppressed more than 2 fold in the successful UCBs comparing with the failed ones (p<0.005, Student’s t-test). Functional annotation analyses revealed that the genes mediated cell growth and cell cycle regulations were enriched in successful UCBs comparing with the failed ones. Our results suggest that the hematopoiesis reconstitution ability may vary among the cryopreserved UCBs and the quality can be distinguished with certain sets of gene expression.
2010-07-15 | GSE19835 | GEO
Project description:Umbilical cord blood (UCB) is a valuable source of hematopoietic stem cells (HSCs) for use in allogeneic transplantation. Key advantages of UCB are rapid availability and less stringent requirements for HLA matching. However, UCB contains an inherently limited HSC count, which is associated with delayed time to engraftment, high graft failure rates and early mortality. 16,16 dimethyl prostaglandin E2 (dmPGE2) was previously identified to be a critical regulator of HSC homeostasis and we hypothesized that a brief ex vivo modulation could improve patient outcomes by increasing the "effective dose" of HSCs. Molecular profiling with Affymetrix GeneChips were used to evaluate if increasing the concentration of prostaglandin at 25 and 37 deg C could increase biological responses. Isolated human CD34+ cells from umbilical cord blood were incubated ex vivo in Stem Span (SS) media evaluating five concentrations of 16,16-dmPGE2 (0.1uM, 1uM, 10uM, 50uM, and 100uM) or Vehicle (DMSO) for 2 hours at 25 or 37 deg C. Total RNA was isolated post incubation and analyzed on Affymetrix microarrays for pathway activation.
2013-09-12 | E-GEOD-48541 | biostudies-arrayexpress
Project description:Umbilical cord blood (UCB) is a valuable source of hematopoietic stem cells (HSCs) for use in allogeneic transplantation. Key advantages of UCB are rapid availability and less stringent requirements for HLA matching. However, UCB contains an inherently limited HSC count, which is associated with delayed time to engraftment, high graft failure rates and early mortality. 16,16 dimethyl prostaglandin E2 (dmPGE2) was previously identified to be a critical regulator of HSC homeostasis and we hypothesized that a brief ex vivo modulation could improve patient outcomes by increasing the “effective dose” of HSCs. Molecular profiling with Affymetrix GeneChips were used to evaluate if increasing the concentration of prostaglandin could compensate for the reduced biological responses observed with incubations at 4 deg C. Isolated human CD34+ from umbilical cord blood were incubated ex vivo in Stem Span (SS) media evaluating three concentrations of 16,16-dmPGE2 (10uM, 50uM, and 100uM) or Vehicle (DMSO) for 2 hours at 4 deg C. To evaluate if increasing the concentration of prostaglandin could compensate for the reduced biological responses observed with incubations at 4 deg C. Total RNA was isolated post incubation and analyzed on Affymetrix microarrays for pathway activation.
2013-09-12 | E-GEOD-46634 | biostudies-arrayexpress
Project description:Umbilical cord blood (UCB) is a valuable source of hematopoietic stem cells (HSCs) for use in allogeneic transplantation. Key advantages of UCB are rapid availability and less stringent requirements for HLA matching. However, UCB contains an inherently limited HSC count, which is associated with delayed time to engraftment, high graft failure rates and early mortality. 16,16 dimethyl prostaglandin E2 (dmPGE2) was previously identified to be a critical regulator of HSC homeostasis and we hypothesized that a brief ex vivo modulation could improve patient outcomes by increasing the “effective dose” of HSCs. Molecular profiling with Affymetrix GeneChips were used to evaluate if prostgandin is required for the entire 2 hour incubation to elicit the maximum pathway activated gene expression response. Isolated human CD34+ from umbilical cord blood were incubated ex vivo in Stem Span (SS) media with 10uM 16,16-dimethyl prostaglandin E2 for varying amounts of time within a two hour incubation window to evaluate if the entire 120 minutes is required to elicit the maximum pathway activated gene expression response or if shorter incubation times were sufficent. Total RNA was isolated post incubation and analyzed on Affymetrix microarrays for pathway activation.
2013-09-12 | E-GEOD-46714 | biostudies-arrayexpress
Project description:Umbilical cord blood (CB) is a non-invasive, convenient and broadly used source of hematopoietic stem cells (HSCs) for allogeneic stem cell transplantation. However, limiting numbers of HSCs remain a major constraint for its clinical application. One feasible option would be to expand HSCs to improve therapeutic outcome, however available protocols and the molecular mechanisms governing the self-renewal of HSC are unclear. Here we show that ectopic expression of a single miRNA, miR-125a, in purified murine and human multipotent progenitors (MPP) resulted in increased self-renewal and robust long-term multi-lineage repopulation in transplanted recipient mice. Using quantitative proteomics and Western blot analysis, we identified a restricted set of miR-125a targets which revealed the involvement of the MAP kinase signaling pathway in conferring long-term repopulating capacity to multipotent progenitors in human and mice. Our findings offer the innovative potential to use MPP with enhanced self-renewal activity to augment limited sources of HSC to improve clinical protocols.
2017-01-11 | PXD003931 | Pride
Project description:We provide an in-depth characterization of engraftable fetal liver (FL) HSCs as these have been shown to possess superior engraftment potential compared to cord blood (CB) and bone marrow (BM) HSCs. We have single cell profiled 26,407 FL cells, of which 7,235 highly-enriched functional FL HSCs, both at the transcriptional and protein level to uncover the detailed molecular signature of engraftment potential.
2021-02-08 | GSE160251 | GEO
Project description:Umbilical cord blood (UCB) is a valuable source of hematopoietic stem cells (HSCs) for use in allogeneic transplantation. Key advantages of UCB are rapid availability and less stringent requirements for HLA matching. However, UCB contains an inherently limited HSC count, which is associated with delayed time to engraftment, high graft failure rates and early mortality. 16,16 dimethyl prostaglandin E2 (dmPGE2) was previously identified to be a critical regulator of HSC homeostasis and we hypothesized that a brief ex vivo modulation could improve patient outcomes by increasing the “effective dose” of HSCs. Molecular profiling with Affymetrix GeneChips were used to determine the optimal ex vivo modulation conditions (e.g., temperature and media) for use in a clinical setting by measured pathway induced expression changes. Isolated human CD34+ from umbilical cord blood were incubated ex vivo in Stem Span (SS) media evaluating three treatment temperatures (4 deg C, 25 deg C, and 37 deg C) with 10uM 16,16-dmPGE2 or Vehicle (DMSO) for 2 hours. To evaluate optimal media, similar CD34+ cells were incubated ex vivo in either Stem Span-SFEM (SS) media or 8% Low Molecular Weigh Dextran 40/5% HSA solution (LMD/HSA) with 10uM 16,16-dmPGE2 or Vehicle (DMSO) for 2 hours at 37 deg C. Total RNA was isolated post incubation and analyzed on Affymetrix microarrays for pathway activation.
2013-09-12 | E-GEOD-46569 | biostudies-arrayexpress