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AA2P-mediated DNA demethylation synergizes with stem cell agonists to promote expansion of stem cells via activation of GAS6/AXL signaling axis [bulkRNA-Seq]

ABSTRACT: To investigate the transcriptional profile of SCACs, STFL expanded and non-cultured CD34+CD45RA- cells

ORGANISM(S): Homo sapiens

PROVIDER: GSE212577 | GEO | 2023/12/18

REPOSITORIES: GEO

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AA2P-mediated DNA demethylation synergizes with stem cell agonists to promote expansion of stem cells via activation of GAS6/AXL signaling axis [scRNA-Seq]

Project description:To investigate the graft composition of SCACs expanded and non cultured CD34+ cells

2023-12-18 | GSE212578 | GEO

AA2P-mediated DNA demethylation synergizes with stem cell agonists to promote expansion of stem cells via activation of GAS6/AXL signaling axis

Project description:This SuperSeries is composed of the SubSeries listed below.

2023-12-18 | GSE212579 | GEO

AA2P-mediated DNA demethylation synergizes with stem cell agonists to promote expansion of hematopoietic stem cells.

Project description:Small molecules have enabled expansion of hematopoietic stem and progenitor cells (HSPCs), but limited knowledge is available on whether these agonists can act synergistically. In this work, we identify a stem cell agonist in AA2P and optimize a series of stem cell agonist cocktails (SCACs) to help promote robust expansion of human HSPCs. We find that SCACs provide strong growth-promoting activities while promoting retention and function of immature HSPC. We show that AA2P-mediated HSPC expansion is driven through DNA demethylation leading to enhanced expression of AXL and GAS6. Further, we demonstrate that GAS6 enhances the serial engraftment activity of HSPCs and show that the GAS6/AXL pathway is critical for robust HSPC expansion.

| S-EPMC10783628 | biostudies-literature

AA2P-mediated DNA demethylation synergizes with stem cell agonists to promote expansion of stem cells via activation of GAS6/AXL signaling axis [bulkRNA-Seq]

Project description:AA2P-mediated DNA demethylation synergizes with stem cell agonists to promote expansion of stem cells via activation of GAS6/AXL signaling axis [bulkRNA-Seq]

| PRJNA876104 | ENA

AA2P-mediated DNA demethylation synergizes with stem cell agonists to promote expansion of stem cells via activation of GAS6/AXL signaling axis

Project description:AA2P-mediated DNA demethylation synergizes with stem cell agonists to promote expansion of stem cells via activation of GAS6/AXL signaling axis

| PRJNA876101 | ENA

AA2P-mediated DNA demethylation synergizes with stem cell agonists to promote expansion of stem cells via activation of GAS6/AXL signaling axis [scRNA-Seq]

Project description:AA2P-mediated DNA demethylation synergizes with stem cell agonists to promote expansion of stem cells via activation of GAS6/AXL signaling axis [scRNA-Seq]

| PRJNA876108 | ENA

Single Cell analysis of the two Human Hematopoietic Stem Cell Populations

Project description:Single cell transcriptomic profiling (sc RNA-seq) of the two Human Hematopoietic Stem Cell Populations: CD34+CD38-CD45RA-CD90+CD49f+ (hereafter CD90+CD49f+) and CD34+CD38-CD45RA-CD90-CD49f+ (hereafter CD90-CD49f+)

2021-07-01 | GSE154931 | GEO

Structural basis for Gas6-Axl signalling.

Project description:Receptor tyrosine kinases of the Axl family are activated by the vitamin K-dependent protein Gas6. Axl signalling plays important roles in cancer, spermatogenesis, immunity, and platelet function. The crystal structure at 3.3 A resolution of a minimal human Gas6/Axl complex reveals an assembly of 2:2 stoichiometry, in which the two immunoglobulin-like domains of the Axl ectodomain are crosslinked by the first laminin G-like domain of Gas6, with no direct Axl/Axl or Gas6/Gas6 contacts. There are two distinct Gas6/Axl contacts of very different size, both featuring interactions between edge beta-strands. Structure-based mutagenesis, protein binding assays and receptor activation experiments demonstrate that both the major and minor Gas6 binding sites are required for productive transmembrane signalling. Gas6-mediated Axl dimerisation is likely to occur in two steps, with a high-affinity 1:1 Gas6/Axl complex forming first. Only the minor Gas6 binding site is highly conserved in the other Axl family receptors, Sky/Tyro3 and Mer. Specificity at the major contact is suggested to result from the segregation of charged and apolar residues to opposite faces of the newly formed beta-sheet.

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Expansion effect of romiplostim on hematopoietic stem and progenitor cells versus other thrombopoietin receptor agonists

Project description:Romiplostim, a thrombopoietin (TPO) receptor agonist, is a clinically approved drug that is clearly effective in reconstituting hematopoiesis in refractory aplastic anemia and　idiopathic thrombocytopenic purpura. However, the mechanism underlying its biological effect is unknown, and its difference with other TPO receptor agonists remains unclear. Therefore, we determined the in vitro expansion effect of romiplostim on human CD34+ hematopoietic stem and progenitor cells (HSPCs) versus recombinant human TPO (rhTPO) and another clinically available drug eltrombopag. We also performed single-cell RNA-seq to define the effect of romiplostim on CD34+ HSPCs at the molecular level. The maximum expansion effect of romiplostim on total CD34+ cells, CD34+CD38+ progenitor cells, and CD34+CD38− immature cells was comparable to that of rhTPO, but higher than that of eltrombopag, particularly on CD34+CD38− immature cells. Single-cell RNA-seq analysis revealed that both romiplostim and eltrombopag induced signatures driven by rhTPO, but romiplostim induced molecular changes related to RHOA signaling at the most primitive subsets in HSPCs that were partially or not driven by eltrombopag. Additionally, romiplostim lacked the ability to induce TFRC expression observed by eltrombopag. In conclusion, romiplostim expands and affects human HSPCs similar to rhTPO but partially different from eltrombopag in terms of induction of gene expression.

2024-09-24 | GSE253936 | GEO

Expression data from human CD34+ HPC subpopulations isolated from umbilical cord blood (Haddad et al. Blood 104:3918, 2004)

Project description:We used microarrays to analyze the gene expression profile of CD34+CD45RA+CD7+, CD34+CD45RA+CD10+CD19- and CD34+CD45+CD7-CD10-CD19- HPCs isolated from umbilical cord blood CD34+CD45RA+CD7+(CD10-) and CD34+CD45RA+CD10+(CD7-CD19-) HPCs correspond respectively to prothymocytes and early pre-proB precursors. CD34+CD45RA+CD7-CD10-CD19- HPCs correspond to lympho-granulo-macrophagic precursors

2011-05-25 | GSE29522 | GEO

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