Papers | |
曾國尊 | A genomic regulatory network for development. Davidson EH, Rast JP, Oliveri P, Ransick A, Calestani C, Yuh CH, Minokawa T, Amore G, Hinman V, Arenas-Mena C, Otim O, Brown CT, Livi CB, Lee PY, Revilla R, Rust AG, Pan Z, Schilstra MJ, Clarke PJ, Arnone MI, Rowen L, Cameron RA, McClay DR, Hood L, Bolouri H. Science. 2002 Mar 1;295:1669-1678. |
安興彥 | "Stemness": transcriptional profiling of embryonic and
adult stem cells. Ramalho-Santos M, Yoon S, Matsuzaki Y, Mulligan RC, Melton DA. Science. 2002 Oct 18;298(5593):579-600. Epub 2002 Sep 12. |
陳建儐 | Hackney JA, Charbord P, Brunk BP, Stoeckert CJ, Lemischka IR,
Moore KA. A molecular profile of a hematopoietic stem cell niche. Proc Natl Acad Sci U S A. 2002 Oct 1;99(20):13061-6. Epub 2002 Sep 11. |
王嘉章 | Lemischka I. Stem cell dogmas in the genomics era. Rev Clin Exp Hematol. 2001 Mar;5(1):15-25. Review. |
魏良泰 | Phillips RL, Ernst RE, Brunk B, Ivanova N, Mahan MA,
Deanehan JK, Moore KA, Overton GC, Lemischka IR. The genetic program of hematopoietic stem cells. Science. 2000 Jun 2;288(5471):1635-40. |
林旭紳 | Wiesmann A, Phillips RL, Mojica M, Pierce LJ, Searles AE,
Spangrude GJ, Lemischka I. Expression of CD27 on murine hematopoietic stem and progenitor cells. Immunity. 2000 Feb;12(2):193-9. |
董建甫 | Petrenko O, Beavis A, Klaine M, Kittappa R, Godin I,
Lemischka IR. The molecular characterization of the fetal stem cell marker AA4. Immunity. 1999 Jun;10(6):691-700. |
羅裕傑 | Moore KA, Ema H, Lemischka IR. In vitro maintenance of highly purified, transplantable hematopoietic stem cells. Blood. 1997 Jun 15;89(12):4337-47. |
邢金良 | Moore KA, Pytowski B, Witte L, Hicklin D, Lemischka IR.
Hematopoietic activity of a stromal cell transmembrane protein containing epidermal growth factor-like repeat motifs. Proc Natl Acad Sci U S A. 1997 Apr 15;94(8):4011-6. |
報告者:安興彥 |
"Stemness": Transcriptional Profiling of Embryonic and
Adult Stem Cells Miguel Ramalho-Santos, Soonsang Yoon, Yumi Matsuzaki, Richard C. Mulligan, Douglas A. Melton Science, Vol. 298, 2002, pp. 597-600 |
英文 |
In this paper, the authors define a
genetic program for stem cells by
comparing the transcriptional profiles of mouse embryonic, neural,
hematopoietic stem cells and two differentiated cells,
the lateral ventricles of the brain and the main cell population of the bone
marrow.
Besides, we can also find that several of these genes are clustered in the genome. When compared to differentiated cell types, stem cells express a significantly higher number of genes whose functions are unknown. There are limitations to the use of oligonucleotide arrays to characterize cells. The analysis is obviously limited to genes present on the microarray, and some RNA transcripts may not be translated into proteins. Another limitation of this study is that it is currently impossible to purify SCs to absolute homogeneity. Genes expressed by contaminating progenitor or differentiated cells may therefore be detected in the SC samples. However, the comparisons used with the corresponding differentiated cell samples should mediate against these "contaminating" genes in subsequent analyses. However, These results still provide a foundation for a more detailed understanding of stem cell biology. And the future goal is to understanding further more about the genetic regulatory networks that stem cells use. |
中文 |
在本篇論文中,作者定義出一套尋找與幹細胞有關的基因的操作程序。在這個程序中,它比較了老鼠的胚胎幹細胞 (ESCs)、神經幹細胞 (NSCs)、造血幹細胞 (HSCs)
以及側腦室細胞 (lateral ventricles of the brain) 與骨髓細胞 (main cell population of the
bone marrow)
這兩種對應的已分化細胞於 DNA 轉錄至 mRNA 過程中的所得到不同資訊。
另外還發現到,其中有些基因在基因組上群聚於相近的位置。當以幹細胞與分化後細胞作比較時,可以明顯地發現在幹細胞中有著更多功能未知的基因。 由於本篇論文的方法是以 Oligonucleotide arrays 作測試,故存在一些限制。有些 RNA 轉錄時並不會轉譯為蛋白質,因此無法被 Oligonucleotide arrays 檢查出來,目前的純化技術尚無法完全分離掉非同類的細胞, 在一份測試樣本中可能會同時包含幹細胞與已分化細胞,這種實驗上的誤差必須想辦法於資料分析前克服。 儘管如此,這些成果對於幹細胞生物學的瞭解,提供了相當重要的基礎。而未來的目標則是希望對於幹細胞所使用的基因調控網路有更多的瞭解。 |
報告者:曾國尊 |
A Genomic Regulatory Network for
Development www.sciencemag.org SCIENCE VOL. 295 1 MARCH 2002 |
英文 |
The authors summarize many results about the biological
reactions, interactions and their relations among one another, and then they
show these relations in a network-like or circuit-diagram-like way. How to
check the correctness of these interactions or to collect such relations is
far beyond our abilities. Howbeit there may be something that we can do, to
formalize this into an algorithm problem. Such as given some interactions
and draw an edge-length-minimum or edge-use-minimum graph. It seems easy,
but how to define the input is difficult. The inputs are involved one
another, some are using "and" gates, some are using "or" gates, and some are
time concerned. It is so complicated to define a perfect input form, much
less to solve such problems. |
中文 |
作者們總結了許多既知的生化反應、交互作用及反應間彼此的關係並且使用網路似(或說電路圖似)的方式將其關係表現出來。如何証實這些反應關係的正確與否、或收集這些反應關係,已非我們這些演算法專長的能力所及。雖則如此,我們依舊可能可以將此正式定義成一演算法之問題。例如給定各物質間之交互作用,要求繪出使用最短邊線總和或使用邊數總和最少的方式之關係圖。這問題看來容易,然而如何定義其輸入(input)卻是極其困難。輸入的各物質間彼此皆有影響,有些需同時成立方會交互作用、有些則是一者成立即可作用、更有些事實上是與時間相關。光是定義出完美的輸入格式就已經如此麻煩,更遑論要解決這樣的問題了。 |
報告者:陳建儐 |
A molecular Profile of a Hematopoietic Stem
Cell Niche Jason A. Hackney, Pierre Charbord, Brian P. Brunk, Christian J. Stoeckert, Ihor R. Lemischka and Kateri A. Moore PNAS(Proceeding of the National Academy of Sciences of the United States of American), Vol. 99, No. 20 |
英文 |
所謂niche是指所指的是讓幹細胞往不同途徑發展的訊號。本篇所研究的是造血幹細胞(HCS)在分子生物層級上的特性。 |
中文 |
所謂niche是指所指的是讓幹細胞往不同途徑發展的訊號。本篇所研究的是造血幹細胞(HCS)在分子生物層級上的特性。 |
報告者:王嘉章 |
Stem Cell Dogmas in the Genomics Era Rev Clin Exp Hematol. 2001 Mar;5(1):15-25. Review. |
英文 |
The most characterized stem cells are those responsible
for hematopoiesis in the mouse and in the human. Over last four decades,
there are some properties found about hematopoiesis. First, stem cells can
control the balance between self-renewal and commitment/differentiation.
Second, stem cells are multipotent, which means that single stem cell can
produce multiple lineage of mature blood cells. Third, stem cells offer a
robust proliferative potential for normal blood cell production. Fourth,
stem cells are rare. Finally, stem cells are quiescent or slowly cycling in
adult hematopoiesis system. |
中文 |
被研究最透徹的幹細胞是在老鼠跟人類的造血細胞,在過去四十年來,對於造血幹細胞有部份的發現。第一,幹細胞有控制自我更新跟分化的平衡的能力;第二,單一幹細胞可製造出多種的成熟細胞;第三,幹細胞提供足夠的造血(細胞)來源;最後,幹細胞在一般的成熟細胞中是處於不活動或低活動量的狀態。 |
報告者:魏良泰 |
The genetic program of hematopoietic stem
cells. Phillips RL, Ernst RE, Brunk B, Ivanova N, Mahan MA, Deanehan JK, Moore KA, Overton GC, Lemischka IR. Science. 2000 Jun 2;288(5471):1635-40. |
英文 |
This paper identifies numerous individual candidate regulatory molecules, but they also pave the way for more global approaches to stem cell biology. A genome-wide gene expression analysis was performed in order to define regulatory pathways in stem cells. Subtracted complementary DNA libraries form highly purified murine fetal liver stem cells were analyzed with bioinformatic and array hybridization strategies. The production of stem cell microarrays will permit the analysis of fluctuations in the genetic program as a function of permutations in self-renewal, commitment, or other stem cell properties. A large percentage of the several thousand gene products that have been characterized correspond to previously undescribed molecules with properties suggestive of regulatory functions. The large collection of gene products will also facilitate proteomic strategies to uncover protein interaction networks. The SCDb will be a resource for the stem cell community and will foster the collaborative and consortial interactions necessary for global approaches to important biological questions. |
中文 |
這篇論文辨識很多獨特的候選調控分子,不過它們也為更總體的接近幹細胞生物學鋪路。 |
報告者:林旭紳 |
Wiesmann A, Phillips RL, Mojica M, Pierce
LJ, Searles AE, Spangrude GJ, Lemischka I. Expression of CD27 on murine hematopoietic stem and progenitor cells. Immunity. 2000 Feb;12(2):193-9. |
英文 |
Hematopoietic stem cells (HSC) are defined by self-renewal and multilineage differentiation potentials. We utilized high-density arrays to compare gene expression in highly purified mouse HSC and their mature progeny. One molecule specifically expressed in immature cells is CD27. The CD27 protein is expressed by about 90% of cells in a purified HSC population. Interestingly, the CD27pos cells are enriched for cells with short-term hematopoietic activities ( colony forming potential in vivo and in vitro ), while the minority CD27neg population is more effective in clonal long-term transplantation. |
中文 |
造血幹細胞(Hematopoietic stem cells,HSC) 具有自我更新和分化成各種血液細胞的能力。我們利用高密度陣列( high-density arrays )來比較高度純化的鼠類HSC以及他們成熟後代的基因表現。在未成熟的細胞中,CD27是一個表現特別明確的分子,在高度純化的HSC族群中約有90%的細胞會表現出CD27蛋白質。有趣的是,CD27pos細胞在短期的造血活動中會被強化(在試管或生物體中形成聚落的能力)。相對少數的CD27neg族群則是在移植的長期持續上較為有效。 |
報告者:董建甫 |
Petrenko O, Beavis A, Klaine M, Kittappa R,
Godin I, Lemischka IR. The molecular characterization of the fetal stem cell marker AA4. Immunity. 1999 Jun;10(6):691-700. |
英文 |
This paper is about identifying and characterizing the stem cell antigen AA4. This molecule is a type I transmembrane protein whose overall structure suggests a role in cell adhesion. During fetal ontogeny (days 9-14 of development), AA4 is expressed in three major cell types: vascular endothelial cells, aorta-associated hematopoietic clusters, and primitive fetal liver hematopoietic progenitors. In the adult, AA4 is abundant in lung, heart, and whole bone marrow. The observations suggest that AA4 plays a role in cell-cell interactions during hematopoietic and vascular development. |
中文 |
這篇paper主要是在做辨識幹細胞抗原AA4 的特徵。其分子是一種type I
透膜蛋白。這種透膜蛋白的整體結構可能在細胞附著時有重要的功能。在老鼠胎兒發展期間(9~14天),AA4主要會在三種細胞表現:內皮血管細胞,動脈相關的造血細胞群,以及原始的胎兒肝造血祖細胞;而在成年期AA4則充斥在成年老鼠的心肺和骨髓。觀察結果顯示AA4可能在造血和血管發展期間細胞與細胞交互作用時扮演著重要的角色。 |
報告者:羅裕傑 |
Moore KA, Ema H, Lemischka IR. In vitro maintenance of highly purified, transplantable hematopoietic stem cells. Blood. 1997 Jun 15;89(12):4337-47. |
英文 |
Mammalian blood formation originates in a small
population of hematopoietic stem cells. However, currently, the only
reliable functional assay system for the most primitive stem cell
compartment is long-term in vivo transplantation. A major challenge in stem
cell research is the establishment of culture systems that facilitate in
vitro maintenance of long-term transplantable stem cell activity. A major
challenge in stem cell research is the establishment of culture systems that
facilitate in vitro maintenance of long-term transplantable stem cell
activity. |
中文 |
哺乳動物血液的來源是由造血幹細胞增生.然而目前研究幹細胞可靠的方法是在活體內移植.在試管內的還沒有較可靠的方法.對於在試管內培養幹細胞的困難再於如何提供給幹細胞的一個增殖環境. |
報告者:邢金良 |
Hematopoietic activity of a stromal cell
transmembrane protein containing epidermal growth factor-like repeat motifs. Moore KA, Pytowski B, Witte L, Hicklin D, Lemischka IR. Proc. Natl. Acad. Sci. USA, Vol. 94, pp. 4011-4016, April 1997, Medical Sciences |
英文 |
Dlk is a transmembrane protein that possesses six
epidermal growth factor-like(EGF-like) sequences at the extracellular
domain, a single transmembrane domain and an intracellular tail. The
extracellular EFG-like region of Dlk can be released by action of an unknown
protease that cuts the extracellular region near the cell membrane. Dlk
belongs to the EGF-like homeotic protein family and plays an important role
in the differential process of cell. Some proteins like Serrate Delta and
Notch are also blong to EGF-like homeotic protein family. Dlk has been
involved in several differentiation processes, such as adipogenesis,
hematopoiesis and neuroendocrine differentiation. |
中文 |
Dlk (delta-like)本身是一種跨膜蛋白質(transmembrane
protein),構造上包含:細胞外區域(extracellular domain)、跨膜區域域(transmembrane domain)
和細胞內區域(intracellular domain)。dlk 的主要構造在於細胞外區域有六個重覆排列的類似表皮細胞生長因(EGF-like)。此外,在這段細胞外的構造上有一處可被酵素作用的切點(proteolytic
processing site),位置約接近細胞膜近側,在經不知名酵素作用後,會產生可溶片段並釋出細胞外去進行作用。dlk 屬於EGF-like
homeotic superfamily 的成員之一,被認為在細胞分化過程中可能扮演重要角色。一些蛋白質如 Serrate、Delta 及Notch
(Serrate 與Delta 的接受體) 與dlk 同屬EGF-like homeotic superfamily 的成員。dlk
的主要功能包括:抑制脂肪細胞形成、協助造血細胞分化成熟以及參與神經內分泌細胞的分化等。 |