生物谷报道：哺乳动物的胰腺是在胚胎发生的过程中由多潜能祖细胞构成，但是这种多潜能祖细胞的性质和功能目前并不了解。最近，科研人员通过对发育中的胰腺的转录因子表达进行广泛的基因组的分析来鉴定基因表达域，这些表达区域可能代表了不同的特定的祖细胞群。这项研究结果发表在最新一期的《Development Cell》杂志上。
研究人员最终鉴定出了5个不同的表达区域。基因谱系示踪技术证实，其中一个定位在胰脏发育分化树顶部的特殊的表达区域，包含有可在体内分化出外分泌细胞，内分泌细胞和导管细胞的多潜能祖细胞。这些多潜能祖细胞是Pdx1+Ptf1a+cMycHighCpa1+ 并且是分化谱系标记阴性的。这些多潜能祖细胞分化出多种不通的终末分化细胞，构成了胰脏发育分化树的不同分支。
这项研究解释了胰腺发育中的多潜能细胞的作用，并建立了一个模型以说明发育过程中的细胞特定类型分化是如何发生的。这对于研究胰腺发育和相关疾病具有重要意义。
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.
原文出处：
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]
作者简介：
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
