Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA265042 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Cell intrinsic alterations underlie hematopoietic stem cell aging
| PRJNA94759 | ENA
Project description:Chronic myelomonocyticleukemia (CMML) is a clinically heterogeneous stem cell malignancy with overlapping features of myelodysplasiaand myeloproliferation. CMML is further subclassified according to percentage of leukemic blasts present in blood or bone marrow, reflecting its intrinsic tendency to progression towards acute myeloid leukemia. Over 90% of CMML patients carry founding mutations in epigenetic and/or splicing genes, which typically involve the primitive stem cell compartment. Thus, transcriptional dysregulation at the stem cell level is likely fundamental to disease onset and progression. However, the critical early hematopoietic stem and progenitor cell (HSPC) subpopulation has not been studied in CMML. We performed single cell RNA sequencing on>6,800 Lin-CD34+CD38-primitive HSPCs from seven CMML patients and three healthy controls. We found substantial inter-and intra-patient heterogeneity, with CMML stem cells displaying distinct transcriptional programs, differentiation potential and cellular signaling pathway priming. Pseudotime analyses revealed that CMML-1/CMML-2 HSPCs have distinct cellular trajectories, indicating that transformation events initiate early within the hematopoietic hierarchy and suggesting against a simple linear clonal evolution dynamic in acute leukemic transformation. We further identified several transcription factors uniquely active in distinct sample subsets. Together our findings provide novel insights into the CMML stem cell compartment, revealing an unexpected degree of transcriptional and subclonal heterogeneity and highlighting early mediators of disease initiation and transformation, of potential translational importance
2020-08-03 | E-MTAB-8884 | biostudies-arrayexpress
Project description:A transcriptome study in mouse hematopoietic stem cells was performed using a sensitive SAGE method, in an attempt to detect medium and low abundant transcripts expressed in these cells. Among a total of 31,380 unique transcript, 17,326 (55%) known genes were detected, 14,054 (45%) low-copy transcripts that have no matches to currently known genes. 3,899 (23%) were alternatively spliced transcripts of the known genes and 3,754 (22%) represent anti-sense transcripts from known genes.
2009-05-20 | GSE16139 | GEO
Project description:CDK6 as key regulator of hematopoietic and leukemic stem cell activation.
| PRJNA262936 | ENA
Project description:A transcriptome study in mouse hematopoietic stem cells was performed using a sensitive SAGE method, in an attempt to detect medium and low abundant transcripts expressed in these cells. Among a total of 31,380 unique transcript, 17,326 (55%) known genes were detected, 14,054 (45%) low-copy transcripts that have no matches to currently known genes. 3,899 (23%) were alternatively spliced transcripts of the known genes and 3,754 (22%) represent anti-sense transcripts from known genes. Mouse hematopoietic stem cells were purified from bone marrow cells using negative and positive selection with a Magnetic-Activated Cell Sorter (MACS). total RNA and mRNA were purified from the purified cells using Trizol reagent and magnetic oligo dT beads. Double strand cDNAs were synthesized using a cDNA synthesis kit and anchored oligo dT primers. After NlaIII digestion, 3’ cDNAs were isolated and amplified through 16-cycle PCR. SAGE tags were released from the 3’ cDNA after linker ligation. Ditags were formed, concatemerized and cloned into a pZERO vector. Sequencing reactions were performed with the ET sequencing terminator kit. Sequences were collected using a Megabase 1000 sequencer. SAGE tag sequences were extracted using SAGE 2000 software.
2009-05-20 | E-GEOD-16139 | biostudies-arrayexpress
Project description:Loss of immune function and an increased incidence of myeloid leukemia are two of the most clinically significant consequences of aging of the hematopoietic system. To better understand the mechanisms underlying hematopoietic aging, we evaluated the cell intrinsic functional and molecular properties of highly purified long-term hematopoietic stem cells (LT-HSCs) from young and old mice. We found that LT-HSC aging was accompanied by cell autonomous changes, including increased stem cell self-renewal, differential capacity to generate committed myeloid and lymphoid progenitors, and diminished lymphoid potential. Expression profiling revealed that LT-HSC aging was accompanied by the systemic down-regulation of genes mediating lymphoid specification and function and up-regulation of genes involved in specifying myeloid fate and function. Moreover, LT-HSCs from old mice expressed elevated levels of many genes involved in leukemic transformation. These data support a model in which age-dependent alterations in gene expression at the stem cell level presage downstream developmental potential and thereby contribute to age-dependent immune decline, and perhaps also to the increased incidence of leukemia in the elderly.
2005-08-16 | E-SMDB-3450 | biostudies-arrayexpress
Project description: Not available
| S-EPMC8784167 | biostudies-literature
Project description:Loss of immune function and an increased incidence of myeloid leukemia are two of the most clinically significant consequences of aging of the hematopoietic system. To better understand the mechanisms underlying hematopoietic aging, we evaluated the cell intrinsic functional and molecular properties of highly purified long-term hematopoietic stem cells (LT-HSCs) from young and old mice. We found that LT-HSC aging was accompanied by cell autonomous changes, including increased stem cell self-renewal, differential capacity to generate committed myeloid and lymphoid progenitors, and diminished lymphoid potential. Expression profiling revealed that LT-HSC aging was accompanied by the systemic down-regulation of genes mediating lymphoid specification and function and up-regulation of genes involved in specifying myeloid fate and function. Moreover, LT-HSCs from old mice expressed elevated levels of many genes involved in leukemic transformation. These data support a model in which age-dependent alterations in gene expression at the stem cell level presage downstream developmental potential and thereby contribute to age-dependent immune decline, and perhaps also to the increased incidence of leukemia in the elderly. 3 old mice and 5 young mice were assayed
2007-12-19 | E-GEOD-4332 | biostudies-arrayexpress
Project description:We found that BAP1 (BRCA1 Associated Protein-1) shows loss of heterozygosity in over 25% of pancreatic cancer patients and functions as tumor suppressor. Conditional deletion of Bap1 in murine pancreas led to genomic instability, accumulation of DNA damage, and an inflammatory response that evolved to pancreatitis with full penetrance. Concomitant expression of oncogenic KrasG12D led to malignant transformation and development of invasive and metastatic pancreatic cancer. At the molecular level, BAP1 maintains the integrity of the exocrine pancreas by regulating genomic stability and its loss confers sensitivity to radio- and platinum-based therapies.
2020-04-14 | GSE121709 | GEO