The CD44+ ALDH+ population of human keratinocytes is enriched for epidermal stem cells with long-term repopulating ability.
The CD44+ ALDH+ population of human keratinocytes is enriched for epidermal stem cells with long-term repopulating ability.
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DOI：
10.1002/stem.1329
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发表时间：
2013-04
期刊：
影响因子：
5.2
通讯作者：
Ghadially, Ruby
中科院分区：
文献类型：
--
作者：
Szabo, Akos Z.;Fong, Stephen;Yue, Lili;Zhang, Kai;Strachan, Lauren R.;Scalapino, Kenneth;Mancianti, Maria Laura;Ghadially, Ruby
与其他体细胞组织一样，分离纯的干细胞群体一直是表皮生物学的主要目标。我们使用先前未经测试的候选干细胞标志物醛脱氢酶（ALDH）和CD 44以及先前研究的整合素α6和CD 71的组合分离新鲜获得的人新生儿角质形成细胞（HNK）的离散群体。使用体内移植试验结合有限稀释分析来量化分离群体中长期重建细胞的富集。ALDH+ CD 44+群体富集了12.6倍的长期再增殖表皮干细胞（EpiSC），整合素α 6 hiCD 71 lo群体富集了5.6倍，超过未分级细胞。除了长期再增殖，CD 44 +ALDH+角质形成细胞表现出其他干细胞特性。CD 44 +ALDH+角质形成细胞具有自我更新能力，表现为表达核Bmi-1的细胞数量增加、连续移植CD 44 +ALDH+细胞和体外全克隆形成。CD 44 +ALDH+细胞是多能的，比CD 44 −ALDH−细胞产生更多的毛囊样结构。此外，58% ± 7%的CD 44 +ALDH+细胞表现出标记保留。在体外，在角质形成细胞和胚胎干细胞生长培养基中，CD 44 +ALDH+细胞显示出增强的集落形成。总之，CD 44 +ALDH+群体表现出干细胞特性，包括长期表皮再生、多能性、标记保留和全克隆形成。这项研究表明，可以使用长期再增殖作为干细胞性质的功能测试来量化人角质形成细胞群体中EpiSC的相对数量。未来的研究将结合联合收割机分离策略，如定量移植测定的结果所示，以获得几乎纯的EpiSC群体。
Like for other somatic tissues, isolation of a pure population of stem cells has been a primary goal in epidermal biology. We isolated discrete populations of freshly obtained human neonatal keratinocytes (HNKs) using previously untested candidate stem cell markers aldehyde dehydrogenase (ALDH) and CD44 as well as the previously studied combination of integrin α6 and CD71. An in vivo transplantation assay combined with limiting dilution analysis was used to quantify enrichment for long-term repopulating cells in the isolated populations. The ALDH+CD44+ population was enriched 12.6-fold for long-term repopulating epidermal stem cells (EpiSCs) and the integrin α6hiCD71lo population was enriched 5.6-fold, over unfractionated cells. In addition to long-term repopulation, CD44+ALDH+ keratinocytes exhibited other stem cell properties. CD44+ALDH+ keratinocytes had self-renewal ability, demonstrated by increased numbers of cells expressing nuclear Bmi-1, serial transplantation of CD44+ALDH+ cells, and holoclone formation in vitro. CD44+ALDH+ cells were multipotent, producing greater numbers of hair follicle-like structures than CD44−ALDH− cells. Furthermore, 58% ± 7% of CD44+ALDH+ cells exhibited label-retention. In vitro, CD44+ALDH+ cells showed enhanced colony formation, in both keratinocyte and embryonic stem cell growth media. In summary, the CD44+ALDH+ population exhibits stem cell properties including long-term epidermal regeneration, multipotency, label retention, and holoclone formation. This study shows that it is possible to quantify the relative number of EpiSCs in human keratinocyte populations using long-term repopulation as a functional test of stem cell nature. Future studies will combine isolation strategies as dictated by the results of quantitative transplantation assays, in order to achieve a nearly pure population of EpiSCs.
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影响因子：
2.2
作者：
Bonnefoix, T;Bonnefoix, P;Sotto, JJ
通讯作者：
Sotto, JJ
DOI：
10.1073/pnas.0603806103
发表时间：
2006-08-01
影响因子：
11.1
作者：
Chute, John P.;Muramoto, Garrett G.;McDonnell, Donald P.
通讯作者：
McDonnell, Donald P.
影响因子：
4
作者：
Budak, MT;Alpdogan, OS;Wolosin, JM
通讯作者：
Wolosin, JM
影响因子：
6.5
作者：
GRIMWOOD, RE;BASKIN, JB;CLARK, RAF
通讯作者：
CLARK, RAF
影响因子：
6.5
作者：
Charruyer, Alexandra;Barland, Chantal O.;Ghadially, Ruby
通讯作者：
Ghadially, Ruby