Anatomic demarcation by positional variation in fibroblast gene expression programs.

Abstract:

:Fibroblasts are ubiquitous mesenchymal cells with many vital functions during development, tissue repair, and disease. Fibroblasts from different anatomic sites have distinct and characteristic gene expression patterns, but the principles that govern their molecular specialization are poorly understood. Spatial organization of cellular differentiation may be achieved by unique specification of each cell type; alternatively, organization may arise by cells interpreting their position along a coordinate system. Here we test these models by analyzing the genome-wide gene expression profiles of primary fibroblast populations from 43 unique anatomical sites spanning the human body. Large-scale differences in the gene expression programs were related to three anatomic divisions: anterior-posterior (rostral-caudal), proximal-distal, and dermal versus nondermal. A set of 337 genes that varied according to these positional divisions was able to group all 47 samples by their anatomic sites of origin. Genes involved in pattern formation, cell-cell signaling, and matrix remodeling were enriched among this minimal set of positional identifier genes. Many important features of the embryonic pattern of HOX gene expression were retained in fibroblasts and were confirmed both in vitro and in vivo. Together, these findings suggest that site-specific variations in fibroblast gene expression programs are not idiosyncratic but rather are systematically related to their positional identities relative to major anatomic axes.

journal_name

PLoS Genet

journal_title

PLoS genetics

authors

Rinn JL,Bondre C,Gladstone HB,Brown PO,Chang HY

doi

10.1371/journal.pgen.0020119

subject

Has Abstract

pub_date

2006-07-01 00:00:00

pages

e119

issue

7

eissn

1553-7390

issn

1553-7404

pii

06-PLGE-RA-0156R1

journal_volume

2

pub_type

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