UCLA scientists and colleagues have created a first-of-its-kind roadmap that traces each step in the development of blood stem cells in the human embryo, providing scientists with a blueprint for producing fully functional blood stem cells in the lab.

这项研究，今天发表在日记中自然, could help expand treatment options for blood cancers like leukemia and inherited blood disorders such as sickle cell disease, saidHanna Mikkola博士of theEli和Edyth在UCLA的再生医学和干细胞研究中心，谁领导了这项研究。

Blood stem cells, also called hematopoietic stem cells, have the ability to make unlimited copies of themselves and to differentiate into every type of blood cell in the human body. For decades, doctors have used blood stem cells from the bone marrow of donors and the umbilical cords of newborns in life-saving transplant treatments for blood and immune diseases. However, these treatments are limited by a shortage of matched donors and hampered by the low number of stem cells in cord blood.

研究人员试图通过试图通过人类多能干细胞在实验室中创建血干细胞来克服这些局限性，这可能会导致体内任何细胞类型。但是成功是难以捉摸的，部分原因是科学家缺乏使实验室生长细胞分化为自我更新的血液干细胞而不是短寿命的血液祖细胞的说明，这只能产生有限的血细胞类型。

“Nobody has succeeded in making functional blood stem cells from human pluripotent stem cells because we didn’t know enough about the cell we were trying to generate,” said Mikkola, who is a professor of molecular, cell and developmental biology in the UCLA College and a member of theUCLA Jonsson Comprehensive Cancer Center.

The new roadmap will help researchers understand the fundamental differences between the two cell types, which is critical for creating cells that are suitable for use in transplantation therapies, said UCLA scientist Vincenzo Calvanese, a co–first author of the research, along with UCLA’s Sandra Capellera-Garcia and Feiyang Ma.

“我们现在有了一本手册，讲述了如何在胚胎中制作造血干细胞，以及它们如何获得使其对患者有用的独特特性，”也是伦敦大学学院的小组负责人卡尔瓦内斯说。该网站上可以向公众使用去识别的数据人造血干细胞发育的地图集。

The research team, which included scientists from Germany’s University of Tübingen and Australia’s Murdoch Children’s Research Institute, created the resource using single-cell RNA sequencing and spatial transcriptomics, new technologies that enable scientists to identify the unique genetic networks and functions of thousands of individual cells and to reveal the location of these cells in the embryo.

数据使得血管干细胞从血管内皮中出现时，并在发育过程中从各个位置迁移，从主动脉开始，最终到达骨髓。重要的是，该地图在其成熟过程中揭示了特定的里程碑，包括它们到达肝脏，在那里他们获得了血干细胞的特殊能力。

为了解释成熟过程，Mikkola将未成熟的血干细胞与有抱负的外科医生进行了比较。正如外科医生需要经历不同的训练阶段以学习如何进行手术一样，未成熟的血液干细胞必须在不同的位置移动才能学习如何作为血液干细胞完成工作。

研究小组还指出了血管壁中的确切前体，从而引起血干细胞。这一发现阐明了关于干细胞的细胞起源以及制造血干细胞而不是血液祖细胞所需的环境的长期争议。

不w that the researchers have identified specific molecular signatures associated with the different phases of human blood stem cell development, scientists can use this resource to see how close they are to making a transplantable blood stem cell in the lab.

“Previously, if we tried to create a blood stem cell from a pluripotent cell and it didn’t transplant, we wouldn’t know where in the process we failed,” Mikkola said. “Now, we can place the cells in our roadmap to see where we’re succeeding, where we’re falling short and fine-tune the differentiation process according to the instructions from the embryo.”

In addition, the map can help scientists understand how blood-forming cells that develop in the embryo contribute to human disease. For example, it provides the foundation for studying why some blood cancers that begin in utero are more aggressive than those that occur after birth.

Mikkola说：“既然我们已经创建了一个在线资源，世界各地的科学家可以用来指导他们的研究，那么真正的工作就开始了。”“这是一个非常激动人心的时刻，因为我们终于会看到我们的劳动成果。”

The research was supported by the National Institutes of Health, the UCLA Jonsson Cancer Center Foundation, the David Geffen School of Medicine at UCLA, the Swedish Research Council, the European Molecular Biology Organization, the Swiss National Science Foundation and the UCLA Broad Stem Cell Research Center (including support from the Rose Hills Foundation and the center’s training program).

参考：Calvanese V，Capellera-Garcia S，Ma F等。将人造血干细胞从血液发作的内皮绘制到出生。自然。2022：1-7。doi：10.1038/S41586-022-04571-X

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