The non-cell-autonomous function of ID1 promotes AML progression via ANGPTL7 from the microenvironment.

The bone marrow microenvironment (BMM) can regulate leukemia stem cells (LSCs) via secreted factors. Increasing evidence suggests that dissecting the mechanisms by which the BMM maintains LSCs may lead to the development of effective therapies for the eradication of leukemia. Inhibitor of DNA binding 1 (ID1), a key transcriptional regulator in LSCs, previously identified by us, controls cytokine production in the BMM, but the role of ID1 in acute myeloid leukemia (AML) BMM remains obscure. Here, we report that ID1 is highly expressed in the BMM of patients with AML, especially in BM mesenchymal stem cells, and that the high expression of ID1 in the AML BMM is induced by BMP6, secreted from AML cells. Knocking out ID1 in mesenchymal cells significantly suppresses the proliferation of cocultured AML cells. Loss of Id1 in the BMM results in impaired AML progression in AML mouse models. Mechanistically, we found that Id1 deficiency significantly reduces SP1 protein levels in mesenchymal cells cocultured with AML cells. Using ID1-interactome analysis, we found that ID1 interacts with RNF4, an E3 ubiquitin ligase, and causes a decrease in SP1 ubiquitination. Disrupting the ID1-RNF4 interaction via truncation in mesenchymal cells significantly reduces SP1 protein levels and delays AML cell proliferation. We identify that the target of Sp1, Angptl7, is the primary differentially expression protein factor in Id1-deficient BM supernatant fluid to regulate AML progression in mice. Our study highlights the critical role of ID1 in the AML BMM and aids the development of therapeutic strategies for AML.

The Taiji Model of Self.

An important theme in the development of self-psychology is the attempt by scholars to construct a self-model with universal cultural adaptability. Among them, representatives are the tripartite model of self-built by Triandis, the theory of the independent self and interdependent self-proposed by Markus and Kitayama, Yang Kuo-Shu's four-part theory of the Chinese self, Hwang Kwang-Kwo's Mandala model of self, and Shiah Yung-Jong's Non-self-Theory. However, these models have a difficult time explaining the structure and development of the Chinese self in Chinese cultural background. After pondering over Chinese traditional culture and the Chinese self, inspired by the archetype of Taiji diagram, in this paper, we construct the Taiji Model of Self. The Taiji Model of Self can not only properly represent the Chinese self-structure, but also explain the growth course of the Chinese self and four kinds of life realms of Chinese people with satisfactory cultural and ecological validity.