10月的《血液》(
Blood)雜誌報導了,瑞典隆德(Lund)大學醫院幹細胞研究中心人員最新總結的調控造血幹細胞的多條信號通路。
造血幹細胞(HSCs)是能自我更新、有較強分化發育和再生能力、可以產生各種類型血細胞的始祖細胞。HSCs是目前研究最為透徹的人類幹細胞。多年來,造血幹細胞一直作為幹細胞生物學研究的基本模型。雖然,已能明確HSCs的功能,並且可以進行純化,但調控HSCs自我更新和分化的分子機制和信號通路仍然是個謎。
近來,Notch、Wnt、Sonic hedgehog (Shh) 和Smad信號通路的研究推進了對HSCs調控的了解。HSCs存在於複雜的骨髓環境中,有著自我更新和分化信號最佳的微環境。這些信號通路使我們能更好地了解HSCs調控、骨髓微環境及外在因素作用於HSCs內部等。
由此,研究者高度關注最新調控造血幹細胞信號通路的進展。(醫學空間)
原始出處:
Blood First Edition Paper, prepublished online October 3, 2007; DOI 10.1182/blood-2007-07-075168.
Submitted July 22, 2007
Accepted September 30, 2007
Signaling pathways governing stem cell fate
Ulrika Blank,
Molecular Med. & Gene Therapy, Inst. of Laboratory Med., & The Lund Strategic Research Center for Stem Cell Biology & Cell Therapy, Lund University Hospital, Lund, Sweden
* Corresponding author; email: stefan.karlsson@med.lu.se .
Hematopoietic stem cells (HSCs) are historically the most thoroughly characterized type of adult stem cell, and the hematopoietic system has served as a principal model structure of stem cell biology for several decades. However, paradoxically, while HSCs can be defined by function and even purified to near-homogeneity, the intricate molecular machinery and the signaling mechanisms regulating fate events such as self-renewal and differentiation have remained elusive. Recently, several developmentally conserved signaling pathways have emerged as important control devices of HSC fate, including Notch, Wnt, Sonic hedgehog (Shh) and Smad pathways. HSCs reside in a complex environment in the bone marrow (BM), providing a niche that optimally balances signals that control self-renewal and differentiation. These signaling circuits provide a valuable structure for our understanding of how HSC regulation occurs, concomitantly with providing information of how the BM microenvironment couples and integrates extrinsic with intrinsic HSC fate determinants. It is the focus of this review to highlight some of the most recent developments concerning signaling pathways governing HSC fate.
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