llecmets

成体干细胞巢，是个挺神秘的东西，是不是所有的成体干细胞都存在实体意义上的niche？这个niche对干细胞的自我更新以及分化启动是如何实现调控的？是通过直接的细胞间接触？还是仅仅是分泌一些因子？现在有明确细胞巢的组织系统大概包含皮肤，胃肠道，神经组织与生殖和造血系统，那么其他组织系统是否也存在明确的干细胞巢？欢迎各位战友整理总结干细胞巢相关文献进展！

littlenapoleon

这篇是讲发现一个掌管胰腺器官发生的多潜能祖细胞区的，文章完全利用原位标记的方法证明了存在这么一个干细胞汇集区。当然文章并未讨论干细胞巢的问题，可是为什么这个多潜能祖细胞区为什么只在胚胎12-15天的具备这个特征，而胚胎15天之后该区域就没有这个干细胞群了？干细胞巢发生了改变？

littlenapoleon

这两篇为walkley在cell上发表的背靠背article，很佩服Walkley，两篇文章同时证明了造血微环境在hsc自我更新和分化调节中发挥作用的关键因子Rb和RARgamma的存在，而且他在前一年已经在pnas上发了篇关于Rb对hsc自我更新的非必需作用研究的文章，第二年又对该基因从另一角度研究了其在造血niche中的关键作用。这样的研究才是真正的研究！
Title: Rb regulates interactions between hematopoietic stem cells and their bone marrow microenvironment
Author(s): Walkley CR (Walkley, Carl R.), Shea JM (Shea, Jeremy M.), Sims NA (Sims, Natalie A.), Purton LE (Purton, Louise E.), Orkin SH (Orkin, Stuart H.)
Source: CELL 129 (6): 1081-1095 JUN 15 2007
Abstract: Hematopoiesis is maintained by stem cells (HSCs) that undergo fate decisions by integrating intrinsic and extrinsic signals, with the latter derived from the bone marrow (BM) microenvironment. Cell-cycle regulation can modulate stem cell fate, but it is unknown whether this represents an intrinsic or extrinsic effector of fate decisions. We have investigated the role of the retinoblastoma protein (RB), a central regulator of the cell cycle, in hematopoiesis. Widespread inactivation of RB in the murine hematopoietic system resulted in profound myeloproliferation. HSCs were lost from the BM due to mobilization to extramedullary sites and differentiation. This phenotype was not intrinsic to HSCs, but, rather, was the consequence of an RB-dependent interaction between myeloid-derived cells and the microenvironment. These findings demonstrate that myeloproliferation may result from perturbed interactions between hematopoietic cells and the niche. Therefore, RB extrinsically regulates HSCs by maintaining the capacity of the BM to support normal hematopoiesis and HSCs.

Title: A microenvironment-induced myeloproliferative syndrome caused by retinoic acid receptor gamma deficiency
Author(s): Walkley CR (Walkley, Carl R.), Olsen GH (Olsen, Gemma Haines), Dworkin S (Dworkin, Sebastian), Fabb SA (Fabb, Stewart A.), Swann J (Swann, Jeremy), McArthur GA (McArthur, Grant A.), Westmoreland SV (Westmoreland, Susan V.), Chambon P (Chambon, Pierre), Scadden DT (Scadden, David T.), Purton LE (Purton, Louise E.)
Source: CELL 129 (6): 1097-1110 JUN 15 2007
Abstract: Myeloproliferative syndromes (IMPS) are a heterogeneous subclass of nonlymphoid hematopoietic neoplasms which are considered to be intrinsic to hematopoietic cells. The causes of MPS are largely unknown. Here, we demonstrate that mice deficient for retinoic acid receptor gamma (RAR gamma), develop MPS induced solely by the RAR gamma-deficient microenvironment. RAR gamma(-/-) mice had significantly increased granulocyte/macrophage progenitors and granulocytes in bone marrow (BM), peripheral blood, and spleen. The MPS phenotype continued for the lifespan of the mice and was more pronounced in older mice. Unexpectedly, transplant studies revealed this disease was not intrinsic to the hematopoietic cells. BM from wild-type mice transplanted into mice with an RAR gamma(-/-) microenvironment rapidly developed the MPS, which was partially caused by significantly elevated TNF alpha in RAR gamma(-/-) mice. These data show that loss of RAR gamma results in a nonhematopoietic cell-intrinsic MPS, revealing the capability of the microenvironment to be the sole cause of hematopoietic

stem_cell

Wnt Signaling in the Niche Enforces Hematopoietic Stem Cell Quiescence and Is Necessary to Preserve Self-Renewal In Vivo.

Cell Stem Cell, Vol 2, 274-283, 06 March 2008

Heather E. Fleming,1,3 Viktor Janzen,1,3 Cristina Lo Celso,1,3 Jun Guo,2 Kathleen M. Leahy,1 Henry M. Kronenberg,2 and David T. Scadden1,3,

1 Center for Regenerative Medicine, Massachusetts General Hospital, Boston, MA 02114, USA
2 Endocrine Unit, Massachusetts General Hospital, Boston, MA 02114, USA
3 Harvard Stem Cell Institute, Cambridge, MA 02138, USA

Wingless (Wnt) is a potent morphogen demonstrated in multiple cell lineages to promote the expansion and maintenance of stem and progenitor cell populations. Wnt effects are highly context dependent, and varying effects of Wnt signaling on hematopoietic stem cells (HSCs) have been reported. We explored the impact of Wnt signaling in vivo, specifically in the context of the HSC niche by using an osteoblast-specific promoter driving expression of the paninhibitor of canonical Wnt signaling, Dickkopf1 (Dkk1). Here we report that Wnt signaling was markedly inhibited in HSCs and, unexpectedly given prior reports, reduction in HSC Wnt signaling resulted in reduced p21Cip1 expression, increased cell cycling, and a progressive decline in regenerative function after transplantation. This effect was microenvironment determined, but irreversible if the cells were transferred to a normal host. Wnt pathway activation in the niche is required to limit HSC proliferation and preserve the reconstituting function of endogenous hematopoietic stem cells.

littlenapoleon

这篇算是最新的总结了几乎所有成干干细胞巢的综述，对于干细胞巢的研究虽然才刚刚开始，但毫无疑问这个方向对体内干细胞的自我更新和分化的理解具有十分重要的意义，而且干细胞巢很可能作为沟通成干和癌干的桥梁逐渐进入研究者的视线。
nature reviews | molecular cell biology volume 9 | january 2008

vnewjay

对于NICHE的理解，我想应该是对一个系统的理解；

Niche包含了很多的内容，比如stem cell周围的基质、周围的细胞因子和周围的其他细胞。

这些因素综合在一起，相互影响构成了一个复杂的系统，例如，细胞因子也许是周围细胞抑或是干细胞自分泌或旁分泌而来的，这些细胞因子有可能直接作用于干细胞本身，也可能先作用于周围的细胞再作用于干细胞。

而对于周围的细胞和干细胞而言，作用也是相互的，如果将干细胞去掉，那么周围的细胞也会发生异常，因此，NICHE又是一个平衡的系统。

基质则作为另外一种重要的因素存在于这个系统中，显然它的作用与细胞和细胞因子完全不同。

研究NICHE，推荐XIE TING的论文，研究的很深入而且很优秀，其阐述了很多有关CAP CELLs和Stem cells的关系，并涉及到了表观遗传所发生的变化。

vnewjay

A good paper for the niches of stem cells !

[ 本帖最后由 vnewjay 于 2008-5-17 22:39 编辑 ]

zhumd

说到niche of stem cell，我这里也有几篇文献贡献出来大家看看

llecmets

很多人总喜欢分出来些所谓的msc来移植，得到些修复的结果就ok，但体内的msc是什么特征？
Stem Cells. 2008 Jun 19.
In Search of the in vivo Identity of Mesenchymal Stem Cells.

da Silva Meirelles L, Caplan AI, Nardi NB.

Departament of Genetics, Universidade Federal do Rio Grande do Sul, Porto Alegre RS, Brazil.

In spite of the advances in the knowledge on adult stem cells (ASCs) during the past few years, their natural activities in vivo are still poorly understood. Mesenchymal Stem Cells (MSCs), one of the most promising types of ASCs for cell-based therapies, are defined mainly by functional assays using cultured cells. Defining MSCs in vitro adds complexity to their study because the artificial conditions may introduce experimental artifacts. Inserting these results in the context of the organism is difficult because the exact location and functions of MSCs in vivo remain elusive; the identification of the MSC niche is necessary to validate results obtained in vitro, and to further the knowledge of the physiological functions of this ASC. Here we show an analysis of the evidence suggesting a perivascular location for MSCs, correlating these cells with pericytes, and present a model in which the perivascular zone is the MSC niche in vivo, where local cues coordinate the transition to progenitor and mature cell phenotypes. This model proposes that MSCs stabilize blood vessels and contribute to tissue and immune system homeostasis under physiological conditions, and assume a more active role in the repair of focal tissue injury. The establishment of the perivascular compartment as the MSC niche provides a basis for the rational design of additional in vivo therapeutic approaches. This view connects the MSC to the immune and vascular systems, emphasizing its role as a physiological integrator and its importance in tissue repair/regeneration.
free for fulltext:
http://stemcells.alphamedpress.org/cgi/reprint/2007-1122v1.pdf

deep

国内有那些实验室在做成体干细胞呢？牛人推荐一下