Abnormal regulation of brain growth in autism results in early overgrowth followed by abnormally slowed growth. Hyperplasia was present in cerebral gray matter and cerebral and cerebellar white matter in early life in patients with autism.

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Although approximately 98% of the internal surface area of the lung is lined by alveolar type I cells, little is known about the functions of this cell type. Using freshly isolated rat type I and type II cells, we created a subtraction library by suppression subtractive hybridization to identify genes differentially expressed by type I cells. We identified twelve genes of known function that are differentially expressed by type I cells. Differential expression of all 12 genes was confirmed by Northern blotting; we confirmed differential expression by immunocytochemistry for 3 genes for which suitable antibodies were available. Most of the genes code for proteins that are multifunctional. From the known functions of these genes, we infer that type I cells may play a role in the maintenance of normal alveolar homeostasis and protection from injury, lung development and remodeling, host defense, tumor/growth suppression, and surfactant metabolism, among other functions.

Freshly isolated rat alveolar type I cells, type II cells, and cultured type II cells have distinct molecular phenotypes. We used microarray analysis with Affymetrix rat chips to determine gene expression profiles of freshly isolated rat type I (TI) and TII cells and cultured TII cells. Our goals were 1) to describe molecular phenotypic "fingerprints" of TI and TII cells, 2) to gain insight into possible functional differences between the two cell types through differentially expressed genes, 3) to identify genes that might indicate potential functions of TI cells, since so little is known about this cell type, and 4) to ascertain the similarities and differences in gene expression between cultured TII cells and freshly isolated TI cells. For these experiments, we used preparations of isolated TI and TII cells that contained Ͻ2% cross-contamination. With a false discovery rate of 1%, 601 genes demonstrated over twofold different expression between TI and TII cells. Those genes with very high levels of differential expression may be useful as markers of cell phenotype and in generating novel hypotheses about functions of TI and TII cells. We found similar numbers of differentially expressed genes between freshly isolated TI or TII cells and cultured TII cells (698, 637 genes) and freshly isolated TI and TII cells (601 genes). Tests of sameness/difference including cluster dendrograms and log/log identity plots indicated major differences between the phenotypes of freshly isolated TI cell and cultured type II cell populations. The latter results suggest that experiments with TII cells cultured under these conditions should be interpreted with caution with respect to biological relevance to TI or TII cells. gene expression profiling; transdifferentiation THE ALVEOLAR EPITHELIUM, which covers Ͼ99% of the very large internal surface area of the lung, comprises two cell types, type I (TI) and type II (TII) cells. TI cells are very large squamous cells with calculated diameters of 50 -100 m and volumes of 3,000 m 3 (56). Two or more very thin (ϳ50 nm) cytoplasmic sheets extend from the nucleus of the TI cell to cover the basement membrane that separates the epithelium from the interstitium. TI cells cover Ͼ98% of the internal surface area of the lungs. In contrast, TII cells are smaller, cuboidal cells (diameter ϳ10 m) characterized morphologically by surfactant-containing secretory granules called lamellar bodies. TI cells have an extremely high water permeability (13) and are capable of transporting ions (4, 33), suggesting that TI cells may play a role in lung liquid homeostasis. Additional functions of TI cells have been proposed, based on the known properties of several genes expressed in this cell type (9, 49, 62). TII cells, which cover the remainder of the alveolar surface, synthesize, secrete, and recycle surfactant components (reviewed in Ref. 51); TII cells also have the capacity to transport ions (26, 45), synthesize immune effector molecules (47, 57, 60), and act as progenitor cells following injury to the ...