Correction: M2 macrophages, but not M1 macrophages, support megakaryopoiesis by upregulating PI3K-AKT pathway activity

In the process of collating the raw data,the authors noticed three images in Fig.4 were used incorrectly.They made an inadvertent mistake by arranging the figure of M2 Group into M2+LY294002 Group in Fig.4k during the revision process.

M2 macrophages,but not Ml macrophages,support megakaryopoiesis by upregulating PI3K-AKT pathway activity

Dysfunctional megakaryopoiesis hampers platelet production,which is closely associated with thrombocytopenia(PT).Macrophages(MΦs)are crucial cellular components in the bone marrow(BM)microenvironment.However,the specific effects of M1 MΦs or M2 MΦs on regulating megakaryocytes(MKs)are largely unknown.In the current study,aberrant BM-M1/M2 MO polarization,characterized by increased M1 MΦs and decreased M2 MΦs and accompanied by impaired megakaryopoiesis-supporting abilities,was found in patients with PT post-allotransplant.RNA-seq and western blot analysis showed that the PI3K-AKT pathway was downregulated in the BM MΦs of PT patients.Moreover,in vitro treatment with PI3K-AKT activators restored the impaired megakaryopoiesis-supporting ability of MΦs from PT patients.Furthermore,we found M1 MΦs suppress,whereas M2 MCDs support MK maturation and platelet formation In humans.Chemical inhibition of PI3K-AKT pathway reduced megakaryopoiesis-supporting ability of M2 MΦs,as indicated by decreased MK count,colony-forming unit number,high-ploidy distribution,and platelet count.Importantly,genetic knockdown of the PI3K-AKT pathway impaired the megakaryopoiesis-supporting ability of MΦs both in vitro and in a MO-specific PI3K-knockdown murine model,indicating a critical role of PI3K-AKT pathway in regulating the megakaryopoiesis-supporting ability of M2 M(Ds.Furthermore,our preliminary data indicated that TGF-β released by M2 MΦs may facilitate megakaryopoiesis through upregulation of the JAK2/STAT5 and MAPK/ERK pathways in MKs.Taken together,our data reveal that M1 and M2 MΦs have opposing effects on MKs in a PI3K-AKT pathway-dependent manner,which may lead to new insights into the pathogenesis of thrombocytopenia and provide a potential therapeutic strategy to promote megakaryopoiesis.

Repair of dysfunctional bone marrow endothelial cells alleviates aplastic anemia

Aplastic anemia(AA)is a life-threatening disease characterized by bone marrow(BM)failure and pancytopenia.As an important component of the BM microenvironment,endothelial cells(ECs)play a crucial role in supporting hematopoiesis and regulating immunity.However,whether impaired BM ECs are involved in the occurrence of AA and whether repairing BM ECs could improve hematopoiesis and immune status in AA remain unknown.In this study,a classical AA mouse model and VE-cadherin blocking antibody that could antagonize the function of ECs were used to validate the role of BM ECs in the occurrence of AA.Nacetyl-L-cysteine(NAC,a reactive oxygen species scavenger)or exogenous EC infusion was administered to AA mice.Furthermore,the frequency and functions of BM ECs from AA patients and healthy donors were evaluated.BM ECs from AA patients were treated with NAC in vitro,and then the functions of BM ECs were evaluated.We found that BM ECs were significantly decreased and damaged in AA mice.Hematopoietic failure and immune imbalance became more severe when the function of BM ECs was antagonized,whereas NAC or EC infusion improved hematopoietic and immunological status by repairing BM ECs in AA mice.Consistently,BM ECs in AA patients were decreased and dysfunctional.Furthermore,dysfunctional BM ECs in AA patients led to their impaired ability to support hematopoiesis and dysregulate T cell differentiation toward proinflammatory phenotypes,which could be repaired by NAC in vitro.The reactive oxygen species pathway was activated,and hematopoiesis-and immune-related signaling pathways were enriched in BM ECs of AA patients.In conclusion,our data indicate that dysfunctional BM ECs with impaired hematopoiesis-supporting and immunomodulatory abilities are involved in the occurrence of AA,suggesting that repairing dysfunctional BM ECs may be a potential therapeutic approach for AA patients.