生物谷報道：哺乳動物的胰腺是在胚胎發(fā)生的過程中由多潛能祖細胞構(gòu)成,，但是這種多潛能祖細胞的性質(zhì)和功能目前并不了解。最近,，科研人員通過對發(fā)育中的胰腺的轉(zhuǎn)錄因子表達進行廣泛的基因組的分析來鑒定基因表達域，這些表達區(qū)域可能代表了不同的特定的祖細胞群。這項研究結(jié)果發(fā)表在最新一期的《Development Cell》雜志上,。
研究人員最終鑒定出了5個不同的表達區(qū)域?；蜃V系示蹤技術(shù)證實,，其中一個定位在胰臟發(fā)育分化樹頂部的特殊的表達區(qū)域,，包含有可在體內(nèi)分化出外分泌細胞，內(nèi)分泌細胞和導(dǎo)管細胞的多潛能祖細胞,。這些多潛能祖細胞是Pdx1+Ptf1a+cMycHighCpa1+ 并且是分化譜系標記陰性的,。這些多潛能祖細胞分化出多種不通的終末分化細胞，構(gòu)成了胰臟發(fā)育分化樹的不同分支,。
這項研究解釋了胰腺發(fā)育中的多潛能細胞的作用,，并建立了一個模型以說明發(fā)育過程中的細胞特定類型分化是如何發(fā)生的。這對于研究胰腺發(fā)育和相關(guān)疾病具有重要意義,。
Figure 1. Genome-Wide TF Expression Analysis of the Developing Pancreas
(A–E) Whole-mount in situ hybridization screen was performed with 1,100 mouse TFs on E14.5 dorsal pancreas. A total of 94 genes showed specific expression that can be classified into five broad patterns, as represented by the expression of Hex, Nr5a2, Pax6, Osr2, and Sox18, respectively.
(F–J) Corresponding section in situ hybridization images of the five patterns. Arrowheads in (G) and (H) indicate tips of the branching pancreatic tree. Pancreatic epithelia are outlined.
(K–O) Schematic drawings of pancreatic gene expression patterns.
原文出處：
Development Cell Volume 13, Issue 1, 3 July 2007, Pages 103-114
A Multipotent Progenitor Domain Guides Pancreatic Organogenesis
Qiao Zhou, Anica C. Law, Jayaraj Rajagopal, William J. Anderson, Paul A. Gray, and Douglas A. Melton
[Summary] [Full Text] [PDF] [Supplemental Data]
作者簡介：
DOUGLAS A. MELTON
Thomas Dudley Cabot Professor of the Natural Sciences
Investigator, Howard Hughes Medical Institute
Research:
Molecular Embryology
Research in our laboratory is focused on the developmental biology of the pancreas. The aim of our research is to understand the genes and cells that direct pancreatic organogenesis. We plan to use that information to grow and develop pancreatic cells (Islets of Langerhans). These goals challenge us to understand the precursors or stem cells that give rise to the pancreas and to characterize the gene products that specify cell fates during organogenesis. We use several vertebrate organisms, including frogs, chickens, and zebrafish, but the majority of our studies are done with mice. In addition, a major focus of our present effort is the differentiation of human embryonic stem cells into pancreatic beta (insulin-producing) cells. We use a variety of techniques including functional genomics and gene arrays for gene discovery, tissue explants and grafting for analyzing inductive signals, and developmental genetics for direct assays of gene function. For more information on our research and group members, see the Melton Lab Homepage.
Selected Publications:
Lammert, E., Cleaver, O. and Melton, D.A. (2001) Induction of Pancreatic Differentiation by Signals from Blood Vessels Science 294: 564 -> Full Text <- !!
Gu, G. Dubauskaite J. and Melton D.A. (2002) Direct evidence for the pancreatic lineage: NGN3+ cells are islet progenitors and are distinct from duct progenitors. Development 129 (10): 2447-57.
Ramalho-Santos, M., Yoon S, Matsuzaki, Y, Mulligan, R.C., Melton, DA. (2002) "Stemness": transcriptional profiling of embryonic and adult stem cells. Science 298(5593):597-600.
Rajagopal, J., Anderson, W.J., Kume, S., Martinez, O.I., Melton, D.A. (2003) Insulin staining of ES cell progeny from insulin uptake. Science 299(5605):363.
Chiang, M.K. Melton, D.A. (2003) Single-cell transcript analysis of pancreas development. Dev. Cell. 4(3):383-393.
Kumar M, and Melton, D. (2003) Pancreas specification: a budding question. Curr. Opinion Genet. Dev. 13:401-401.
Murtaugh LC, Stanger BZ, Kwan KM, Melton DA. (2003) Notch signaling controls multiple steps of pancreatic differentiation. Proc Natl Acad Sci USA. Dec 9; 100(25): 14920-5.
Gu G., Wells JM, Dombkowski D., Preffer F., Aronow B., Melton DA. (2004) Global expression analysis of gene regulatory pathways during endocrine pancreatic development. Development 131 (1):165-179.
Cowan C.A., Klimanskaya I, McMahon J., Atienza J., Witmyer J., Zucker JP, Wang S., Morton CC, McMahon AP, Powers D, and Melton DA. (2004) Derivation of embryonic stem-cell lines from human blastocysts. N Engl J Med 350;13, 1353-1356
