Japanese Research Team Proposes New Model For Blood Cells Lineages Development

According to hematopoietic stem cells (HSC) model, the two progenitor cell types, T and B cells, lose the potential to develop into non-lymphocytes (myeloid cells) once they pass the common lymphoid progenitor (CLP) branching point.

However, the Japanese researchers proposed a different picture in which progenitor cells retain the potential to generate myeloid cells across all branches of development.

In the current research, the researchers sought to substantiate this theory by pinpointing the moment at which T cell progenitors lose the potential to develop into myeloid cells, a key step in determining cell fate..

The researchers said that in the experiments with mouse hematopoietic stem cells (HSC) cultured on immobilised delta-like 4 proteins, the researchers found that progenitors developing toward T cells were arrested in the absence of feeder cells, which support survival and growth.

The arrested cells then entered a cycle of self-renewal in which they replicated but did not further develop. Testing of various conditions revealed that reduction of the cytokine interleukin-7 (IL-7), possibly corresponding to an environmental signal in the thymus, triggered resumption of development and differentiation into T cells.

Finally, the researchers discovered that T cell progenitors in the thymus from mice deficient in the gene Bcl11b exhibited the same halted development and self-renewal cycle, while further experiments connected up-regulation of the transcription factor encoded by this gene to IL-7 levels.,

Together, the findings identify Bcl11b as a ‘master gene’ governing the final step toward differentiation into T cells thereby confirming the proposed model.