Nature: Humans first induced functional hematopoietic stem cells in the laboratory

Recently, researchers at Weill Cornell Medicine of Cornell University have discovered an innovative approach to directly transform endothelial cells into transformed hematopoietic stem cells, which is expected to yield healthy blood cells for life. The results, published in Nature, represent the first time humans have created hematopoietic stem cells in the laboratory.

“This is a breakthrough in changing the rules of the game, not only bringing us closer to the healing of blood diseases, but also revealing the complex biological mechanisms behind stem cell self-renewal,” said the author of the article, Professor Shahin Rafii.

Corresponding author Shahin Rafii (Source: Cornell University)

“This is a very exciting result because it provides us with a way to produce normal stem cells that are large enough for clinical transplantation, helping us to eventually cure hereditary or acquired blood diseases,” another article Professor Joseph Scandura said.

The researchers found that these vascular endothelial cells themselves create a microenvironment for the development of hematopoietic stem cells, which can be called vascular niche cells. They introduced the genes of Fosb, Gfi1, Runx1 and Spi1 transcription factors into the vascular endothelial cells of adult mice and expressed them into paracrine factors of vascular endothelial cells, which turned them into hematopoietic with self-renewal ability. stem cell. In addition, inhibition of TGFβ and CXCR7, as well as activation of BMP and CXCR4 signaling pathways, can facilitate this process.

Specifically, vascular endothelial cells are transformed into three stages. From 0-8 days after the introduction of the foreign gene, the induction phase, during which vascular endothelial cells begin to express the key transcription factor Runx1 of hematopoietic stem cells. In the subsequent 8-20 day differentiation phase, the above hematopoietic stem cells are transformed into hematopoietic stem cells, which are maintained without the expression of Fosb, Gfi1, Runx1 and Spi1. The 20-28 days after cell fate determination is the expansion phase, when newly formed hematopoietic stem cells self-proliferate in a large amount, and have a similar transcriptome and long-term self-renewal ability as normal adult hematopoietic stem cells.

Hematopoietic stem cells (green) transformed from vascular endothelial cells (ash) (Source: Nature)

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