07 January 2019

Human skin cells have been converted successfully into blood stem cells for the first time – bringing new therapies for people with blood diseases a step closer, it has been announced.

The international project, led by researchers at Lund University in Sweden, follows research reported a couple of years ago when they converted mouse skin cells into blood stem cells.

The team, which included scientists from Sweden, USA, Russia, and Portugal, used the same combination of transcription factors as in that mouse study to convert human fibroblasts into haematopoietic cells. The full findings – the first time that the mechanism of blood stem cell reprogramming has been described – are published in the journal Cell Reports.

“This is a first step on the way to generating fully functional blood stem cells in a petri dish which, in the future, could be transplanted into patients with blood disease,” said lead researcher Filipe Pereira, from Lund University.

“Skin cells are easily accessible and simple to reproduce in test tubes, which means that they could constitute an unlimited source of cells for transplantation. Blood stem cells, on the other hand, lose important properties when they are cultivated.”

The process takes between 15 and 25 days, during which time the skin fibroblasts undergo a dynamic transition mirroring the birth of blood stem cells during embryonic development.

The researchers found that the collaboration between the three transcription factors was important to induce haemogenesis. GATA2, one of the transcription factors, leads the process and recruits the two other factors, GFI1B and FOS, into accessible regions of the genome. This leads to the skin cell programme being silenced and the activation of haemogenesis, which results in the reprogramming of the skin cell into a blood stem cell.

“So far, this is basic research, but it has great potential for development into treatment. Before we get to that stage, we are learning quite a lot about the genetic program of blood stem cells,” added Pereira.

Source: Gomes, A.M., Kurochkin, I., Chang, B., Daniel, M., Law, K., Satija, N., Lachmann, A., Wang, Z., Ferreira, L., Ma'ayan, A., Chen, B.K., Papatsenko, D., Lemischka, I.R., Moore, K.A., Pereira, C.-F., (2018) “Cooperative Transcription Factor Induction Mediates Hemogenic Reprogramming”, Cell Reports, available at doi: 10.1016/j.celrep.2018.11.032


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