Single-cell RNA-seq reveals heterogeneity in hiPSC-derived muscle progenitors and E2F family as a key regulator of proliferation.
Single-cell RNA-seq reveals heterogeneity in hiPSC-derived muscle progenitors and E2F family as a key regulator of proliferation.
复制标题
DOI：
10.26508/lsa.202101312
复制
发表时间：
2022-08
影响因子：
4.4
通讯作者：
Sakurai, Hidetoshi
中科院分区：
文献类型：
--
作者：
Nalbandian, Minas;Zhao, Mingming;Kato, Hiroki;Jonouchi, Tatsuya;Nakajima-Koyama, May;Yamamoto, Takuya;Sakurai, Hidetoshi
本研究鉴定并表征了四种不同的来源于人诱导多能干细胞的肌肉祖细胞群体。人多能干细胞衍生的肌肉祖细胞（hiPSC-MuPC）类似于胎儿期肌肉祖细胞，并具有体内再生能力。然而，hiPSC-MuPC的异质性是未知的，这可能会影响这些细胞的再生潜力。在这里，我们通过对hiPSC-MuPC培养物进行单细胞RNA测序建立了hiPSC-MuPC图谱。生物信息学分析揭示了hiPSC-MuPC的四个细胞簇：肌细胞、定向祖细胞、循环祖细胞和非循环祖细胞。使用FGFR 4作为非循环祖细胞和循环细胞的标志物，并使用CD 36作为定型细胞和肌细胞的标志物，我们发现FGFR 4+细胞比CD 36+细胞具有更高的再生能力。我们还鉴定了E2 F转录因子家族是hiPSC-MuPC增殖的关键调节因子。我们的研究提供了对具有更高再生潜力的hiPSC-MuPCs的纯化的见解，并增加了对hiPSC-MuPCs转录调控的理解。
This study identified and characterized four different populations of muscle progenitor cells derived from human induced pluripotent stem cells. Human pluripotent stem cell-derived muscle progenitor cells (hiPSC-MuPCs) resemble fetal-stage muscle progenitor cells and possess in vivo regeneration capacity. However, the heterogeneity of hiPSC-MuPCs is unknown, which could impact the regenerative potential of these cells. Here, we established an hiPSC-MuPC atlas by performing single-cell RNA sequencing of hiPSC-MuPC cultures. Bioinformatic analysis revealed four cell clusters for hiPSC-MuPCs: myocytes, committed, cycling, and noncycling progenitors. Using FGFR4 as a marker for noncycling progenitors and cycling cells and CD36 as a marker for committed and myocyte cells, we found that FGFR4+ cells possess a higher regenerative capacity than CD36+ cells. We also identified the family of E2F transcription factors are key regulators of hiPSC-MuPC proliferation. Our study provides insights on the purification of hiPSC-MuPCs with higher regenerative potential and increases the understanding of the transcriptional regulation of hiPSC-MuPCs.
登录
查看更多内容
影响因子：
4.6
作者：
Piasecka A;Sekrecki M;Szcześniak MW;Sobczak K
通讯作者：
Sobczak K
影响因子：
5.9
作者：
Nalbandian M;Zhao M;Sasaki-Honda M;Jonouchi T;Lucena-Cacace A;Mizusawa T;Yasuda M;Yoshida Y;Hotta A;Sakurai H
通讯作者：
Sakurai H
影响因子：
12.4
作者：
Negroni, Elisa;Riederer, Ingo;Mouly, Vincent
通讯作者：
Mouly, Vincent
DOI：
10.1073/pnas.1808303116
发表时间：
2019-03-05
影响因子：
11.1
作者：
Incitti, Tania;Magli, Alessandro;Perlingeiro, Rita C. R.
通讯作者：
Perlingeiro, Rita C. R.
影响因子：
3.7
作者：
Lilja KC;Zhang N;Magli A;Gunduz V;Bowman CJ;Arpke RW;Darabi R;Kyba M;Perlingeiro R;Dynlacht BD
通讯作者：
Dynlacht BD