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Genes differentially expressed by acutely isolated resident progenitor cells of the human white matter

a technology of resident progenitor cells and genes, which is applied in the field of genes differentially expressed by acutely isolated resident progenitor cells of the human white matter, can solve the problems that no studies to date have specifically examined the environment of adult human white matter, and achieve the effect of modulating the production of neurons and/or

Inactive Publication Date: 2005-08-11
CORNELL RES FOUNDATION INC
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

[0007] The present invention relates to a method of modulating production of neurons and/or oligodendrocytes from neural progenitor cells of human white matter. This involves administering an a

Problems solved by technology

Yet no studies to date have specifically examined the environment of the adult human white matter from the standpoint of steady-state cues and cell-specific responsiveness by resident progenitor cells.

Method used

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  • Genes differentially expressed by acutely isolated resident progenitor cells of the human white matter
  • Genes differentially expressed by acutely isolated resident progenitor cells of the human white matter
  • Genes differentially expressed by acutely isolated resident progenitor cells of the human white matter

Examples

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example 1

[0036] Adult Human Subcortical White Matter

[0037] Adult human subcortical white matter was obtained from temporal lobe tissue removed from 48 patients at craniotomy, principally for medication-refractory epilepsy (age 17-56 years; 5 males and 3 female). Samples were obtained from patients who consented to tissue use under protocols approved by the New York Hospital-Cornell, Columbia Presbyterian Hospital, and University of Rochester-Strong Memorial Hospital Institutional Review Boards. The tissues were prepared and white matter progenitor cells freshly isolated as previously described (Nunes et al., “Identification and Isolation of Multipotential Neural Progenitor Cells from the Subcortical White Matter of the Adult Human Brain.”Nat Med 9: 439-447 (2003), which is hereby incorporated by reference in its entirety). Briefly, samples were minced into PIPES solution (in mM: 120 NaCl, 5 KCl, 25 glucose, and 20 PIPES), then digested in papain-PIPES (11.4 U / ml papain; Worthington, Freehol...

example 2

[0038] Affymetrix GeneChip Protocol

[0039] Immediately after sorting, RNA was extracted with Trizol (Invitrogen) and then purified using RNeasy (Qiagen), both according to manufacturer's specifications. 100 ng of total RNA was amplified using Affymatrix's small sample protocol (GeneChip® Eukaryotic Small Sample Target Labeling Technical Note), and 15 μg of cRNA was used on each U95Av2 GeneChip.

example 3

[0040] Analysis of GeneChip Expression Data

[0041] Image files were processed using MAS5.0 to produce CHP files. Images were masked to remove streaks or smears present, and no scaling of data was performed during analysis. Data was then imported into GeneSpring (5.0, Silicon Genetics) and per chip normalization performed (using the 50th percentile of all measurements in that sample). Calculation of gene expression ratios was then performed by comparing the expression pattern of each A2B5-sorted sample to that of the unsorted population from which it had been extracted. This comparison effectively normalized sample-to-sample variation. The arithmetic mean ratio of A2B5-sorted to unsorted was then calculated from three separate patients. An estimate of error was generated using the Rocke-Lorenzato global error model, which takes into account the variability in the expression level of individual genes, compared to that of the entire data set. As a result, lower and more variably expres...

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Abstract

The present invention relates to a method of modulating production of neurons and / or oligodendrocytes from neural progenitor cells of human white matter and to a method of treating a subject for a condition modulated by underproduction of oligodendrocytes from human white matter. Both of these methods involve administering an agonist or antagonist of one or more molecules set forth in Tables 1 and / or 2 to the neural progenitor cells. Also disclosed is a method of using an inhibitor of sterol synthesis to differentiate oligodendrocyte progenitor cells to oligodendrocytes.

Description

[0001] This application claims the benefit of U.S. Provisional Patent Application Ser. No. 60 / 519,310, filed Nov. 10, 2003.[0002] The subject matter of this application was made with support from the United States Government under NINDS Grant No. R01NS33106 and R01NS39559. The U.S. Government may have certain rights.FIELD OF THE INVENTION [0003] The present invention is directed to genes differentially expressed by acutely isolated resident progenitor cells of the human white matter. BACKGROUND OF THE INVENTION [0004] An abundant population of glial progenitor cells resides in the adult human subcortical white matter. These cells give rise to myelinogenic oligodendrocytes upon transplantation, yet when removed from the tissue environment they behave as multipotential neurogenic progenitors. To identify genes that regulate their homeostasis and cell fate decisions of these adult progenitor cells, the transcriptional profile of A2B5+ white matter progenitor cells (WMPCs) sorted from h...

Claims

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Application Information

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IPC IPC(8): A61KA61K31/737A61K38/17G01N33/68
CPCA61K31/737G01N2800/28G01N2500/00G01N33/6896A61K31/555A61P21/00A61P25/00A61P25/28
Inventor GOLDMAN, STEVEN A.SIM, FRASER
Owner CORNELL RES FOUNDATION INC
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