HSC - Princeton/UPenn SCGAP Group

The focus of the project is on the elucidation of the mechanisms that regulate the establishment of the hematopoietic stem and progenitor cell hierarchy in the human system. Our interdisciplinary team consists of six individual laboratories: Ihor Lemischka & Kateri Moore (Molecular biology, cDNA libraries, and microarrays); Paul Simmons (Stem and progenitor cell purification, in vitro assays, NOD/SCID assays); Esmail Zanjani (In utero sheep assays); Chris Stoeckert (Computational analysis, bioinformatics); Lyle Ungar (Network modeling).

SCGAP-HSC, Harvard

The aim of our project focuses on utilizing a comparative genomics approach to understand the specification, maintenance, and regulation of hemagioblasts and hematopoietic stem cells. This project is a joint effort of seven laboratories as Leonard I. Zon (zebrafish transgenics, cell sorting, gene knockdown and knock out), Yi Zhou (cDNA libraries, microarray, and informatics), Stuart Orkin (mouse ES cells differentiation, cell sorting, gene knockout), A. Tom Look (in situ hybridization analysis), George Church (computational analysis), Christine and Bernard Thisse (in situ hybridization analysis), Zhu Chen (EST sequencing and analysis).

Liver, HSC-Baylor SCGAP

The goals of the liver progenitor cell project are to carry out gene expression profiling using Affymetrix arrays on three types of progenitor cells; 1.) Bi-potential mouse embryo liver (BMEL) cells (isolated and initially characterized by Strick-Marchand and Weiss, Hepatology, 2002, 36:794-804) that differentiate into hepatocytic or cholangiocytic cells under particular culture conditions, 2.) oval cells fractionated from inured liver, and 3.) side population cells from the adult liver that efflux the dye, Hoechst 33342. The genes that are differentially expressed in the undifferentiated BMEL progenitors, oval cells, and SP cells will be determined and compared to other stem cell populations including HSC and other adult tissue progenitor cells. These liver progenitor gene lists will be used to identify surface markers that may enable the identification and isolation of progenitor cells in normal liver.

Goals of the hematopoietic cell project are 1.) to compare the gene expression profiles of single HSCs to examine the heterogeneity of the HSC population, 2.) to understand the similarities and differences in gene expression between proliferating and quiescent HSCs and 3.) to identify those genes whose expression distinguishes fetal liver HSCs from those in adult bone marrow.

Bone cell GAP

Our work focuses on developing biological and computational resources that are crucial to understanding how the osteoprogenitor lineage provides a renewing source of osteoblast for embryogenesis, somatic growth, bone fracture repair and states of estrogen deficiency. Our team consists of four major groups. David Rowe, Leonardo Aguila, Ivo Kalajzic, Stephen Clark (Cell identification and isolation, in vivo ice assays); Winfried Krueger (cDNA libraries, microarrays); Barbara Kream, Alex Lichtler & John Harrison (murine models); Dong-Guk Shin, Luke Achenie & Hsin-wei Wang (Computational analysis and bioinformatics).

Prostate/Bladder cell GAP

We are investigating the molecular basis of cell-cell interaction in the differentiation of epithelial cells of the human prostate and bladder. Our approach involves cell-type identification by CD cell surface molecules, isolation of specific cell populations, gene expression analysis, and functional test of candidate genes in a cell culture system. This is a collaboration between Urology and Pathology at the University of Washington and the Institute for Systems Biology.

Kidney cell GAP

This group aims to characterize the processes of normal kidney development so as to identify novel secreted factors which can be used to train embryonic stem cells to adopt fate and novel transmembrane proteins which will mark their progress along this path and allow the selective enrichment of these populations. The team is Australian-based, mult-inodal and multidisciplinary with expertise in bioinformatics, expression profiling and cell biology (Dr. Sean Grimmond, Dr. Rohan Teasdale, Institute for Molecular Bioscience); renal development and molecular genetics (Associate Professor Melissa Little, Professor David Hume, Institute for Molecular Bioscience; Professor John Bertram, Dr. Georgina Caruana, Monash University) and murine and human embryonic stem cell biology (Dr. Andrew Perkins, Monash University, Associate Professor Martin Pera, Monash Institute of Reproduction and Development).

Gut cell GAP

We are conducting a molecular analysis of epithelial progenitors present in the adult mouse stomach and small intestine. These cells are being harvested from gnotobiotic transgenic mouse models where their representation is enriched. We are sequencing (Rick Wilson, Sandra Clifton, Washington University Genome Sequencing Center) normalized micro-cDNA libraries (Mike Lovett) prepared from laser capture microdissected (LCM) progenitors (Thad Stappenbeck), and analyzing the datasets using a variety of computational/bioinformatic methods (Jason Mills). We are relating what is found in mice to the normal adult human gut by profiling expression of selected genes in LCM progenitor compartments.