Cell：区别胚胎与成人干细胞的基因

生物谷

    生物谷报道：在干细胞的理解上，一个发现填充了一个重要的缺口，研究人员已经发现一种蛋白质--胚胎（而非成人）的造血干细胞，需要自我补充。研究者提出找到胚胎造血干细胞特殊的调控路径可以帮助科学家理解儿童白血病，以及让骨髓移植体产生造血干细胞。哈佛Hughes医学研究所的研究者Sean J. Morrison和位于密西根州的大学的同事于2007年7月26日在细胞学杂志的在线公布上发表了他们的结果。
    干细胞是不成熟的细胞，可以分化成多种多样的细胞类型，在自我更新的过程中，它们也会自我补充。造血干细胞产生红细胞及许多类型的白细胞。研究人员发现，在一生的不同阶段的不同干细胞有很大的不同。相比于一生不同阶段的相同组织的干细胞，一生相同阶段的不同组织的干细胞是更具有相似性的。一生中不同阶段的干细胞之间有一个很明显的不同，即它们经常通过不同的机制来自我更新。研究人员已经发现存在着成人特定的机制，这暗示一定存在着一些胚胎特定的机制。但是还没有人发现调控胚胎（非成人）造血干细胞自我更新的基因。
    Morrison 和他的同事过去一直在比较不同发展阶段的造血干细胞的基因表达模式。他们已经发现了少量的随阶段的不同活力不同的基因。其中一个叫Sox17。人们认为Sox17调节早期胚胎细胞的形成，然后继续发展成内胚层组织象胰腺及血管的内皮。但是，Morrison提出还不知道Sox17对造血干细胞有什么作用。
    当研究者击昏老鼠的Sox17，老鼠不能形成它们的造血系统。同时，研究人员监测了在特定细胞内或生长的特定阶段内能够清除Sox17的老鼠。他们发现击昏已经形成造血系统的胚胎小鼠的基因会引起造血干细胞的消失。这说明在干细胞维持自身发展时同样需要Sox17。另外，清除成年老鼠的Sox17基因对造血系统并没有作用。研究者发现当造血干细胞从具有高度活力的胚胎干细胞到比较缓慢分化的成人干细胞的成熟的过程中，Sox17的作用停止了。
    因此，在胚胎/新生儿的干细胞鉴定的许多不同方面，这个基因可能是被广泛需要的。这填补了科学家在理解维持胚胎（非成年）造血细胞调控机制上的一个大漏洞。同时，对胚胎干细胞自我更新的理解可以帮助科学家理解新生儿出生缺陷及儿童癌症。

原文出处：

Sox17 Dependence Distinguishes the Transcriptional Regulation of Fetal from Adult Hematopoietic Stem Cells

Injune Kim, Thomas L. Saunders, and Sean J. Morrison
10.1016/j.cell.2007.06.011
[PDF] [Supplemental Data]

相关基因：

SOX17

Official Symbol SOX17 and Name: SRY (sex determining region Y)-box 17 [Homo sapiens]
Other Aliases: FLJ22252
Other Designations: SRY-box 17; SRY-related HMG-box transcription factor SOX17
Chromosome: 8; Location: 8q11.23
Annotation: Chromosome 8, NC_000008.9 (55533048..55535484)
MIM: 610928
GeneID: 64321

作者简介：

Sean J. Morrison, Ph.D.
Associate Professor of Cell & Developmental Biology
Associate Professor of Internal Medicine (Molecular Medicine and Genetics)
Investigator, Howard Hughes Medical Institute
Director, University of Michigan Center for Stem Cell Biology
Henry Sewall Professor in Medicine
Go to Sean Morrison's Lab
Community of Science Profile
Publications listed in PubMed

Stem cells are self-renewing multipotent progenitors that give rise to all of the other cells in particular tissues. For example, hematopoietic stem cells (HSCs) are the rare cells in bone marrow that give rise to all blood and immune system cells. Neural crest stem cells give rise to a number of different tissues including the peripheral nervous system. Given their seminal roles in development and regeneration, stem cells define the nexus of important questions in both developmental biology and clinical applications. We study stem cell biology using hematopoiesis and neural development as model systems. The next challenge in stem cell biology will be to integrate what we know about stem cells in different tissues in order to understand common mechanisms of regulation and distinctions that permit tissue-appropriate development. Our work on stem cell regulation encompasses both molecular and cellular questions, from the role of transcription factors in cell fate determination to changes in the properties of stem cells during aging. We have decided to focus on mechanisms that regulate stem cell self-renewal, stem cell aging, and organogenesis from stem cells. By studying these mechanisms in parallel using stem cells from two different tissues we will assess the extent to which different types of stem cells employ similar or different mechanisms to regulate these critical functions.

Representative Publications:

Bixby, S., G.M.. Kruger, J.T. Mosher, N. Joseph, and S.J. Morrison. 2002. Cell-intrinsic differences between neural stem cells from different regions of the peripheral nervous system regulate the generation of neural diversity. Neuron 35:643-656.
Kruger, G.M., J. Mosher, S. Bixby, N. Joseph, T. Iwashita, and S.J. Morrison. 2002. Neural crest stem cells persist in the adult gut but undergo perinatal changes in self-renewal potential, neuronal subtype potential, and responsiveness to lineage determination factors. Neuron 35:657-669.
Kruger, G.M. and S.J. Morrison. 2002 Brain repair by endogenous progenitors. Cell 110:399-402.
Iwashita, T., G.M. Kruger, R. Pardal, M.J. Kiel, and S.J. Morrison. 2003. Hirschsprung disease is linked to defects in neural crest stem cell function. Science 301:972-976.
Alvarez-Dolado, M., R. Pardal, J.M. Garcia-Verdugo, J.R. Fike, H.O. Lee, K. Pfeffer, C. Lois, S.J. Morrison and A. Alvarez-Buylla. 2003. Fusion of bone-marrow-derived cells with Purkinje neurons, cardiomyocytes and hepatocytes. Nature 425:968-973.
Molofsky, A.V., R. Pardal, T. Iwashita, I-K. Park, M.F. Clarke, and S.J. Morrison. 2003. Bmi-1 dependence distinguishes neural stem cell self-renewal from progenitor proliferation. Nature 425:962-967.
Al-Hajj, M., M.S. Wicha, A. Benito-Hernadez, S.J. Morrison, and M.F. Clarke. 2003. Prospective identification of tumorigenic breast cancer cells. PNAS USA 100:3983-3988
Pardal, R., M.F. Clarke, and S. J. Morrison. 2003. Applying the principles of stem cell biology to cancer. Nature Reviews Cancer 3:895-902.
Kiel, M.J., O.H. Yilmaz, T. Iwashita, O.H. Yilmaz, C. Terhorst, and S.J. Morrison. 2005. SLAM family receptors distinguish hematopoietic stem and progenitor cells and reveal endothelial niches for stem cells. Cell 121: 1109-1121