Tissue‐specific differences in the proportion of mosaic large NF1 deletions are suggestive of a selective growth advantage of hematopoietic del(+/−) stem cells
Tissue‐specific differences in the proportion of mosaic large NF1 deletions are suggestive of a selective growth advantage of hematopoietic del(+/−) stem cells
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嵌合大 NF1 缺失比例的组织特异性差异提示造血 del( /â) 干细胞的选择性生长优势
DOI：
10.1002/humu.22013
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发表时间：
2012
期刊：
影响因子：
3.9
通讯作者：
Kehrer-Sawatzki H
中科院分区：
文献类型：
--
作者：
Roehl AC;Mussotter T;Cooper DN;Kluwe L;Wimmer K;Högel J;Zetzmann M;Vogt J;Mautner VF;Kehrer-Sawatzki H
跨越1.2 Mb的2型NF 1缺失通常是合子后起源的，因此往往与正常细胞和携带缺失的细胞（del（+/−）细胞）的嵌合现象有关。通过FISH研究了11例镶嵌2型缺失患者，在全血和分离的CD 3+、CD 14+、CD 15+和CD 19+白细胞中检测到高比例（94-99%）del（+/−）细胞。然而，在尿源性上皮细胞中观察到del（+/−）细胞的比例显著较低（24 - 82%）。一名携带非典型大NF 1缺失且具有非复发性断点的患者也被发现血液中del（+/−）细胞的比例（96%）远高于尿液（51%）。在这些嵌合体患者中观察到的del（+/−）细胞比例以及X染色体失活（XCI）模式的组织特异性差异表明，大多数缺失发生在XCI发作前的植入前囊胚期之前或期间。我们假设，造血del（+/−）干细胞在早期发育阶段的特点是选择性生长优势，比正常细胞缺乏删除，导致高比例的del（+/−）细胞在外周血中的影响。Mutat 33：541-550，2012.© 2011 Wiley Periodicals，Inc.
Type‐2NF1deletions spanning 1.2 Mb are frequently of postzygotic origin and hence tend to be associated with mosaicism for normal cells and those harboring the deletion (del(+/−) cells). Eleven patients with mosaic type‐2 deletions were investigated by FISH and high proportions (94–99%) of del(+/−) cells were detected both in whole blood and in isolated CD3+, CD14+, CD15+, and CD19+ leukocytes. Significantly lower proportions of del(+/−) cells (24‐82%) were however noted in urine‐derived epithelial cells. A patient harboring an atypical largeNF1deletion with nonrecurrent breakpoints was also found to have a much higher proportion of del(+/−) cells in blood (96%) than in urine (51%). The tissue‐specific differences in the proportions of del(+/−) cells as well as the X chromosome inactivation (XCI) patterns observed in these mosaic patients suggest that the majority of the deletions had occurred before or during the preimplantation blastocyst stage before the onset of XCI. We postulate that hematopoietic del(+/−) stem cells present at an early developmental stage are characterized by a selective growth advantage over normal cells lacking the deletion, leading to a high proportion of del(+/−) cells in peripheral blood from the affected patients. Hum Mutat 33:541–550, 2012. © 2011 Wiley Periodicals, Inc.
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影响因子：
20.3
作者：
P. Emanuel;Lana J. Bates;R. Castleberry;R. Gualtieri;K. Zuckerman
通讯作者：
P. Emanuel;Lana J. Bates;R. Castleberry;R. Gualtieri;K. Zuckerman
五种人类细胞类型的原始细胞库大小和谱系关系*
影响因子：
1.9
作者：
P. Fialkow
通讯作者：
P. Fialkow
影响因子：
158.5
作者：
Side, L;Taylor, B;Shannon, K
通讯作者：
Shannon, K
2 型 NF1 缺失非常不寻常，因为不存在非等位基因同源重组热点并且明显偏好雌性有丝分裂重组。
影响因子：
9.8
作者：
Katharina Steinmann;D. Cooper;L. Kluwe;N. Chuzhanova;C. Senger;E. Serra;C. Lázaro;M. Gilaberte;K. Wimmer;V. Mautner;H. Kehrer
通讯作者：
H. Kehrer
影响因子：
5.3
作者：
Sharp, A;Robinson, D;Jacobs, P
通讯作者：
Jacobs, P