Stepwise Reprogramming of B Cells into Macrophages

  title={Stepwise Reprogramming of B Cells into Macrophages},
  author={Huafeng Xie and Min Ye and Ru Feng and Thomas Graf},

Figures from this paper

Reprogramming of B cells into macrophages: mechanistic insights

The findings show that the conversion of pre-B cells to macrophages does not involve overt retrodifferentiation and that high concentrations of C/EBPα bypass the cell cycle-dependency of immune cell transdifferentiation.

Transcriptional regulation of early B cell development

This work provides a provisional model for understanding the molecular basis for B cell developmental biology and establishes a conceptual framework for understanding how and why aging leads to the loss of early B cell precursors.

The order of expression of transcription factors directs hierarchical specification of hematopoietic lineages.

It is proposed that the order of expression of key transcription factors is critical for their interplay to selectively drive lineage specification programs, by which stem cells could generate multiple lineage cells in a hierarchical manner.

Role of transcription factors in differentiation and reprogramming of hematopoietic cells.

It is shown that virtually all progenitors, including CLPs, CMPs, GMPs, and MEPs, still retain differentiation plasticity, and they can be converted into lineages other than their own by ectopic activation of only a single lineage-specific transcription factor.

HEBAlt enhances the T-cell potential of fetal myeloid-biased precursors.

It is proposed that HEBAlt plays a role in the network that enforces the T-lineage fate and limits myeloid fate during hematopoiesis.

Logical modeling of lymphoid and myeloid cell specification and transdifferentiation

Focusing on B-cell and macrophage development, a qualitative dynamical model recapitulating cytokine-induced differentiation of common progenitors, the effect of various reported gene knockdowns, and the reprogramming of pre-B cells into macrophages induced by the ectopic expression of specific transcription factors is defined.

PU.1 and C/EBPα/β convert fibroblasts into macrophage-like cells

The data suggest that it might become possible to induce the transdifferentiation of skin-derived fibroblasts into cell types desirable for tissue regeneration, and the effects of PU.1 and C/EBPα on fibro Blasts are examined.



PU.1 induces myeloid lineage commitment in multipotent hematopoietic progenitors.

It is shown that the Ets family transcription factor PU.1 specifically instructs transformed multipotent hematopoietic progenitors to differentiate along the myeloid lineage, suggesting the existence of a bilineage intermediate.

Commitment to the B-lymphoid lineage depends on the transcription factor Pax5

It is shown that pro-B cells lacking Pax5 are also incapable of in vitro B-cell differentiation unless Pax5 expression is restored by retroviral transduction, and Pax5 plays an essential role in B-lineage commitment by suppressing alternative lineage choices.

Distinct C/EBP functions are required for eosinophil lineage commitment and maturation.

Results show that C/EBP can induce both myeloid and eosinophil lineage commitment and that transactivation independent and dependent C/ EBP functions are required during eos inophil Lineage commitment and maturation, respectively.

Cell-fate conversion of lymphoid-committed progenitors by instructive actions of cytokines

It is concluded that cytokine signalling can regulate cell-fate decisions and proposed that a critical step in lymphoid commitment is downregulation of cytokine receptors that drive myeloid cell development.

Transcriptional regulation of granulocyte and monocyte development

Granulocytes and monocytes develop from a common myeloid progenitor and can be induced by Maf-B, c-Jun, or Egr-1 and is dependent upon PU.1, Sp1, and ICSBP.

Regulation of macrophage and neutrophil cell fates by the PU.1:C/EBPα ratio and granulocyte colony-stimulating factor

It is demonstrated here that haploinsufficiency for the gene encoding the transcription factor PU.1 partially suppresses the neutropenia of mice deficient in granulocyte colony-stimulating factor.

GATA-1 reprograms avian myelomonocytic cell lines into eosinophils, thromboblasts, and erythroblasts.

The results suggest that GATA-1 is a lineage-determining transcription factor in transformed hematopoietic cells, which not only activates lineage-specific genetic programs but also suppresses myelomonocytic differentiation.

Regulation of B lymphocyte and macrophage development by graded expression of PU.1.

Using retroviral transduction of PU.1 complementary DNA into mutant hematopoietic progenitors, it is demonstrated that differing concentrations of the protein regulate the development of B lymphocytes as compared with macrophages.