Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 100, Issue 4, Pages 2088-2093Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0337659100
Keywords
stem cell; plasticity; cell fusion; cell fate change
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Funding
- NHLBI NIH HHS [R01 HL065572, HL65572] Funding Source: Medline
- NIA NIH HHS [R37 AG009521, AG09521, R01 AG020961, R01 AG009521, AG20961] Funding Source: Medline
- NICHD NIH HHS [R01 HD018179, HD18179] Funding Source: Medline
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We show here that cells within human adult bone marrow can contribute to cells in the adult human brain. Cerebellar tissues from female patients with hematologic malignancies, who had received chemotherapy, radiation, and a bone marrow transplant, were analyzed. Brain samples were obtained at autopsy from female patients who received male (sex-m is matched) or female (sex-matched, control) bone marrow transplants. Cerebella were evaluated in 10-mum-thick, formaldehyde-fixed, paraffin-embedded sections that encompassed up to approximate to50% of a human Purkinje nucleus. A total of 5,860 Purkinje cells from sex-mismatched females and 3,202 Purkinje cells from sex-matched females were screened for Y chromosomes by epifluorescence. Confocal laser scanning microscopy allowed definitive identification of the sex chromosomes within the morphologically distinct Purkinje cells. In the brains of females who received male bone marrow, four Purkinje neurons were found that contained an X and a Y chromosome and two other Purkinje neurons contained more than a diploid number of sex chromosomes. No Y chromosomes were detected in the brains of sex-matched controls. The total frequency of male bone marrow contribution to female Purkinje cells approximated 0.1%. This study demonstrates that although during human development Purkinje neurons are no longer generated after birth, cells within the bone marrow can contribute to these CNS neurons even in adulthood. The underlying mechanism may be caused either by generation de novo of Purkinje neurons from bone marrow-derived cells or by fusion of marrow-derived cells with existing recipient Purkinje neurons.
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