Putative Regulators for the Continuum of Erythroid Differentiation Revealed by Single-cell Transcriptome of Human BM and UCB Cells[scRNA-seq]
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ABSTRACT:
PROVIDER: PRJNA633550 | ENA |
REPOSITORIES: ENA
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Project description:Fine-resolution differentiation trajectories of adult human hematopoietic stem cells (HSC) involved in the generation of red cells is critical for understanding dynamic developmental changes that accompany human erythropoiesis. Using Single-cell RNA sequencing (scRNA-seq) of primary human terminal erythroid cells (CD34−CD235a+) isolated directly from adult bone marrow (BM) and umbilical cord blood (UCB), we documented the transcriptome of terminally differentiated human erythroblasts at unprecedented resolution. The insights enabled us to distinguish polychromatic erythroblasts (PolyE) at the early and late stages of development as well as the different development stages of orthochromatic erythroblasts (OrthoE). We further identified a set of putative regulators of terminal erythroid differentiation and functionally validated three of the identified genes, AKAP8L, TERF2IP and RNF10, by monitoring cell differentiation and apoptosis. We documented that knockdown of AKAP8L suppressed the commitment of HSC to erythroid lineage and cell proliferation, and delayed differentiation of colony forming unit-erythroid (CFU-E) to the proerythroblast stage (ProE). In contrast, the knockdown of TERF2IP and RNF10 delayed differentiation of PolyE to OrthoE stage. Taken together, the convergence and divergence of the transcriptional continuums at single-cell resolution underscore the transcriptional regulatory networks that underlie human fetal and adult terminal erythroid differentiation.
2020-05-25 | GSE150774 | GEO
Project description:Fine-resolution differentiation trajectories of adult human hematopoietic stem cells (HSCs) involved in the generation of red cells is critical for understanding dynamic developmental changes that accompany human erythropoiesis. Using single-cell RNA sequencing (scRNA-seq) of primary human terminal erythroid cells (CD34-CD235a+) isolated directly from adult bone marrow (BM) and umbilical cord blood (UCB), we documented the transcriptome of terminally differentiated human erythroblasts at unprecedented resolution. The insights enabled us to distinguish polychromatic erythroblasts (PolyEs) at the early and late stages of development as well as the different development stages of orthochromatic erythroblasts (OrthoEs). We further identified a set of putative regulators of terminal erythroid differentiation and functionally validated three of the identified genes, AKAP8L, TERF2IP, and RNF10, by monitoring cell differentiation and apoptosis. We documented that knockdown of AKAP8L suppressed the commitment of HSCs to erythroid lineage and cell proliferation and delayed differentiation of colony-forming unit-erythroid (CFU-E) to the proerythroblast stage (ProE). In contrast, the knockdown of TERF2IP and RNF10 delayed differentiation of PolyE to OrthoE stage. Taken together, the convergence and divergence of the transcriptional continuums at single-cell resolution underscore the transcriptional regulatory networks that underlie human fetal and adult terminal erythroid differentiation.
| S-EPMC7293633 | biostudies-literature
Project description:Variation of UCB CD34+ in erythroid differentiation potential
| PRJNA763126 | ENA
Project description:Preeclampsia (PE) has been associated with placental dysfunction, resulting in foetal hypoxia, accelerated erythropoiesis and increased erythroblast count in the umbilical cord blood (UCB). Although the detailed effects remain unknown, placental dysfunction can also cause inflammation, nutritional and oxidative stress in the fetus that can affect erythropoiesis. Here, we compared the expression of surface adhesion molecules and erythroid differentiation capacity of UCB hematopoietic stem/ progenitor cells (HSPCs), UCB erythroid profiles along with transcriptome and proteome of these cells between male and female foetuses from PE and normotensive pregnancies. While no significant differences were observed in UCB HSPC migration/ homing and in vitro erythroid colony differentiation, the UCB HSPC transcriptome and the proteomic profile of the in vitro differentiated erythroid cells differed between PE vs normotensive samples. Accordingly, despite absence of significant differences in the UCB erythroid populations in male or female foetuses from PE or normotensive pregnancies, transcriptional changes were observed during erythropoiesis, particularly affecting male foetuses. Pathway analysis suggested deregulation in mTORC1/AMPK signaling pathways controlling cell cycle, differentiation and protein synthesis. These results associate PE with transcriptional and proteomic changes in foetal HSPCs and erythroid cells that may underlie the higher erythroblast count in the UCB in PE.
2019-06-20 | PXD010364 | Pride
Project description:We investigated the miRNA expression in ex vivo human erythroid cultures from umbilical cord blood (UCB)-derived CD34 cells. Hypothetically, the decline of certain miRNAs may promote erythropoiesis by unblocking expression of key functional proteins while the up-regulation of other miRNAs may block commitment to non-erythroid lineages. Therefore, discovering the patterns and sequence of miRNA expression during hematopoietic differentiation will provide insights about the functional roles of these tiny noncoding genes. Keywords: miRNA expression profiling
2007-04-01 | GSE6000 | GEO
Project description:Ex vivo manufactured red blood cells (RBC) generated from immortalized erythroid cell lines which can semi-infinitely grow are expected to become a significant alternative in future transfusion therapies. To establish those cell lines, ectopic expression of human papilloma virus (HPV) E6/E7 gene has successfully been employed. In order to induce differentiation and maturation of the immortalized cell lines, terminating the HPV-E6/E7 expression through a gene induction system has been believed to be essential. Here we report that erythroid cell lines established from human bone marrow using simple overexpression of HPV-E6/E7 is capable of normal erythroid differentiation without turning the gene expression off. Newly established cell lines, Erythroid Lines from Lund University (ELLU), are able to differentiate towards mature cells including enucleated reticulocytes upon changing the culture condition but without terminating HPV-E6/E7 gene expression. ELLU cells are heterogeneous, and unexpectedly, clones expressing adult hemoglobin rapidly differentiate but produced cells are fragile while other clones with fetal hemoglobin start expressing adult hemoglobin upon differentiation and give rise to more mature cells. Our findings propose an alternative method to establish immortalized human erythroid cell lines and describe novel cellular characteristics for desired functionally competent clones.
2022-01-31 | GSE184083 | GEO
Project description:Umbilical cord blood (UCB) transplantation shows pro-angiogenic effect and contributes to symptom amelioration in animal models of cerebral infarction. OP9 is a stromal cell line used as feeder cells to promote hematoendothelial differentiation of embryonic stem cells. We co-cultured UCB 24hr with OP9 (i.e. OP9 preconditioning) and investigated its change in angiogenic properties and underlying mechanisms. Single cell RNA sequencing showed prominent phenotypic shift toward M2 in monocytic fraction of OP9 pre-conditioned UCB.
2023-01-25 | GSE207249 | GEO
Project description:Single cell studies elucidating the transcriptional continuum underpinning lineage commitment in the human bone marrow (BM) have advanced the understanding of hematopoiesis beyond the classic hierarchical model. However, T-lineage commitment, which occurs in the thymus remains incompletely defined. We mapped single cell transcriptomes spanning post-natal human thymopoiesis including the earliest progenitors. Instead of previously described discrete populations, transcriptional and lineage assay data resolved a continuum of novel cell states within CD34+ thymic progenitor cells. The initial stages of thymopoiesis involve multilineage priming of single cells followed by a gradual transition to T-commitment, a continuum previously undescribed outside the BM. Early progenitors express a hematopoietic stem cell (HSC) like profile but unlike HSC show initiation of T-priming. Species related differences exist in the earliest progenitor cells.
2020-06-12 | GSE139042 | GEO
Project description:The main aim of this study was to assess the changes in blood gene expression in UCB patients and to identify genes serving as biomarkers for UCB diagnosis and progression. Our study characterized the comprehensive expression profile of UCB and highlighted differences in expression patterns between UCB and healthy control
2020-01-24 | GSE138118 | GEO