Project description:Hematopoietic stem cells (HSCs) are characterized by their ability to generate all blood cells while retaining their self-renewal capacity. While it is convenient to believe that HSCs represent a homogenous population, several evidences do not support this notion. Here we identified and characterized a HSC population that expressed CD93 on their membrane. This population showed strong molecular dHSC signature, combined with activation features. Thereby, suggesting that they represent an intermediate state between quiescent and active HSCs being more prone to respond upon alterations in the hematopoietic lineage
Project description:Hematopoietic stem cells (HSCs) are characterized by their ability to generate all blood cells while retaining their self-renewal capacity. While it is convenient to believe that HSCs represent a homogenous population, several evidences do not support this notion. Here we identified and characterized a HSC population that expressed CD93 on their membrane. This population showed strong molecular dHSC signature, combined with activation features. Thereby, suggesting that they represent an intermediate state between quiescent and active HSCs being more prone to respond upon alterations in the hematopoietic lineage
Project description:Leukemia stem cells (LSCs) share several crucial properties with hematopoietic stem cells (HSCs) including self-renewal, cell cycle quiescence, and expression of a CD34+CD38- immunophenotype, which complicates efforts to eradicate AML by therapeutically targeting LSCs without adversely affecting HSCs. Here we report that CD93, a C-type lectin transmembrane receptor, is preferentially expressed on the cell surface of LSCs compared with HSCs in the genetic subtype of AML with genomic rearrangements of the MLL gene. LSCs that selectively express CD93 are actively cycling, and highly enriched for xeno-engraftment potential, yet comprise a minor component of an otherwise quiescent CD34+CD38- compartment of human AML. Notably, CD93 is required for LSC function in MLL leukemogenesis, and is not simply a passive surface marker co-expressed on LSCs. Thus, CD93 selectively marks and essentially maintains LSCs, and identifies them as predominantly cycling, non-quiescent leukemia-initiating cells in MLL-rearranged AML.
Project description:IL-17D/CD93 axis was essential for ILC3s hemostasis. In order to further understand how IL-17D-CD93 axis regulate ILC3s function, we conducted RNA-seq analysis of ILC3s.
Project description:To further decipher CD93-dependent pathways, we compared global expression profiles of ischemic (ipsilateral) hemispheres of CD93-deficient mice (CD93-ko) with expression profiles of wild-type mice. Total RNA obtained from CD93-ko and WT mice at different time points after cerebral ischemia and from untreated brain tissue
Project description:We isolated ECs from anti-CD93 antibody treated or control KPC tumor and performed RNA-seq to investigate genome-wide expression changes in response to the treatment of anti-CD93. Many of the genes affected by anti-CD93 were functionally related to cell adhesion, angiogenesis or vasculature development. Gene ontology analysis further confirmed that the transcriptomic changes by anti-CD93 were mainly related to biological pathways of angiogenesis, cell adhesion, or vasculature development.
Project description:Astrogenesis is repressed in the early embryonic period, and occurs in the late embryonic period. A variety of external and internal signals contribute to the sequential differentiation of neural stem cell. Here, we discover that the immune-related CD93 plays a critical role in the onset of astrogenesis in mouse. CD93 expression is detected in neural stem cell and neuron but bot in astrocyte, and declines as differentiation proceeds. CD93 knockout increases astrogenesis at the expense of neuron production during the late embryonic period. CD93 responds to the ECM protein MMRN2 to trigger the repression of astrogenesis. In mechanism, CD93 delivers the signal through a series of phosphorylation cascade to β-Catenin, then β-Catenin transfers to nucleus to activate Zfp503 transcription. The transcription repressor ZFP503 inhibits Gfap transcription by binding to the Gfap promoter with the help of Grg5. Furthermore, the abnormal differentiation in astrogenesis and neurogenesis caused by CD93 knockout results in autism-like behaviors. Taken together, our study reveals that CD93 is a negative regulator in controlling the proper time of astrogenesis, and provides a new sight in therapy for psychiatric disorders.
