做hematopoiedtic stem cell 必看的一篇最新文献

饶冠华

Nature. 2012 Jan 25;481(7382):457-62. doi: 10.1038/nature10783.
1 r' E  y! w* x& X- u1 CEndothelial and perivascular cells maintain haematopoietic stem cells.
! s* M4 \2 ~, e6 ~7 WDing L, Saunders TL, Enikolopov G, Morrison SJ./ e) e5 v6 S7 l3 M: e+ p) j
SourceHoward Hughes Medical Institute, Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA.2 N4 j1 Y5 {' A# ^( D& `5 i
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Abstract
5 l8 `, v4 g4 g7 \) K8 G4 Y5 }2 ASeveral cell types have been proposed to create niches for haematopoietic stem cells (HSCs). However, the expression patterns of HSC maintenance factors have not been systematically studied and no such factor has been conditionally deleted from any candidate niche cell. Thus, the cellular sources of these factors are undetermined. Stem cell factor (SCF; also known as KITL) is a key niche component that maintains HSCs. Here, using Scf(gfp) knock-in mice, we found that Scf was primarily expressed by perivascular cells throughout the bone marrow. HSC frequency and function were not affected when Scf was conditionally deleted from haematopoietic cells, osteoblasts, nestin-cre- or nestin-creER-expressing cells. However, HSCs were depleted from bone marrow when Scf was deleted from endothelial cells or leptin receptor (Lepr)-expressing perivascular stromal cells. Most HSCs were lost when Scf was deleted from both endothelial and Lepr-expressing perivascular cells. Thus, HSCs reside in a perivascular niche in which multiple cell types express factors that promote HSC maintenance, m# Y$ Q& z% U$ U4 ]: s

刘森泉

这篇文章主要亮点在于发现了这一类内皮细胞和表达Lepr的间质细胞维持HSC生长这样一个现象。但是离应用还有很大距离，比如作者是通过SCF来筛选支持细胞的，证明了这一部分细胞的确很重要，但是不能把这种细胞分来作基质吧，如果要开发基质细胞来促进HSC分化或扩增维持等，这些细胞不仅仅靠SCF来发挥作用的，还有很多未知的其他因素，所以还需要不断研究这些细胞和普通的基质细胞还有哪些地方不同。个人拙见。

饶冠华

回复 刘森泉 的帖子
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, o. ]2 g& C: F) o1 p* t嗯 说的很对，这篇文章针对HSC niche目前有疑问或者争论的地方都给出了很直接的证据，另外关于成骨细胞对维持HSC有重要作用提出了质疑。sean morrison 实验室除了做了SCF相关的工作之外，把其它几种重要的niche因子也一并分析了一下，比如CXCL12还有Angiopoietin-1。至于能否把这些作为体外培养HSC来开发，我觉得还是很有曙光的，至少这个迈出了重要的一步。

cicadacjk

还没看，先讨论下
$ m3 _3 I! W9 V7 E' g/ A1 }这个结果很重要，但对于解决目前这些争议和实际的技术问题应该还不是很有力（从摘要看）
: [. G5 X; ^9 E' Z# @7 o比如niche角度，只能证明这类细胞分泌的SCF很重要，不能证明其他细胞分泌的其他因子不重要& ^/ l3 }8 A; [' W/ d2 V2 ?2 }
从应用角度，摆脱基质细胞体外扩增是重点，还是要立足于发现niche中能够维持HSC不分化增殖的新的重要因子。

benne21

thanks!

robbie_vipcn

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