一种新的干细胞--可以形成功能组织

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来自Salk Institute的研究者发现了一种新的干细胞，它们具有形成成熟，有功能组织的能力。这一发现被发布在May 6, 2015 in Nature。在报道中研究者首次发明一种可靠的方法将人的干细胞和不可发育的小鼠胚胎细胞在体外共培养，从而使这些人干细胞分化为早期胚胎组织。
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% n1 ~* [: b8 f$ h8 W, c& F研究者将这些新的干细胞命名为region-selective pluripotent stem cells（rsPSCs）。相比于传统的人多能干细胞，这些rsPSCs更容易在实验室中培养，以及应用于细胞替换治疗（大规模生产以及基因修饰也具有优势）。% S; s/ q# h* p# [& l" k
Salk Professor Juan Carlos Izpisua Belmonte, senior author of the paper and holder of Salk's Roger Guillemin Chairb说：“我们发现的the region-specific cells可以应用于实验室研究人类发育，进化和疾病，同时提供了新的治疗途径。”8 c- j8 k' N1 Y$ |) w
为了产生这些细胞，Salk的研究者建立了一个多信号诱导体系可以诱导培养皿中的人干细胞spatially oriented。然后他们将这些human rsPSCs注射到部分切除的小鼠胚胎中在培养皿中培养36h。同时，他们也用传统方式培养的人干细胞进行相同的注射，从而比较出他们技术的优越性。传统的干细胞无法整合到胚体中，但是rsPSCs可以整合，发育出早期的胚胎组织，这些胚胎细胞可以进行动态变化，形成各种细胞，组织和器官。事实上，这些 rsPSCs开始分化胚胎早期的三胚层（ectoderm, mesoderm and endoderm）。研究者终止了这些细胞的进一步发育，但是每一胚层的细胞理论上可以形成特异的组织和器官。
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该研究的另一个合作者the labs of Salk Professors Joseph Ecker and Alan Saghatelian, the Izpisua Belmonte team 检测了rsPSCs的一些特征，结果显示：这些细胞有不同的分子特征，代谢途径以及表观修饰（patterns of chemical modifications to DNA that control which genes are turned on or off without changing the DNA sequence）。
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Jun Wu, a postdoctoral researcher in Izpisua Belmonte's lab and first author of the new paper说："The region selective-state of these stem cells is entirely novel for laboratory-cultured stem cells and offers important insight into how human stem cells might be differentiated into derivatives that give rise to a wide range of tissues and organs.Not only do we need to consider the timing, but also the spatial characteristics of the stem cells. Understanding both aspects of a stem cell's identity could be crucial to generate functional and mature cell types for regenerative medicine."
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" e# p" Z. B+ a/ s; a) a& k2 p感觉这个细胞状态非常特别，不知道是否可以用于异种胚胎嵌合实验，比如人猪嵌合。这个细胞的筛选角度也非常特别。希望有进一步的发展。' a" M# {! `* U9 C$ I- y9 Q
New stem cells hold potential for generating mature functional tissues8 c3 e/ u0 y7 O0 d& B8 Z
Date:
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Source:
8 v! k! n. C0 I( ?" e! }Salk Institute for Biological Studies0 i/ a/ Y, o' C& p6 Y$ L9 w
Summary:
( K5 M# i5 q, B: @Scientists have discovered a new type of stem cell that could potentially generate mature, functional tissues. They report using these new stem cells to develop the first reliable method for integrating human stem cells into nonviable mouse embryos in a laboratory dish in such a way that the human cells began to differentiate into early-stage tissues.
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Scientists at the Salk Institute have discovered a novel type of pluripotent stem cell -- cells capable of developing into any type of tissue -- whose identity is tied to their location in a developing embryo. This contrasts with stem cells traditionally used in scientific study, which are characterized by their time-related stage of development.
0 I+ }9 _( ]1 b. GIn the paper, published May 6, 2015 in Nature, the scientists report using these new stem cells to develop the first reliable method for integrating human stem cells into nonviable mouse embryos in a laboratory dish in such a way that the human cells began to differentiate into early-stage tissues.: b9 [3 A+ B- L7 s" w( ~8 p
"The region-specific cells we found could provide tremendous advantages in the laboratory to study development, evolution and disease, and may offer avenues for generating novel therapies," says Salk Professor Juan Carlos Izpisua Belmonte, senior author of the paper and holder of Salk's Roger Guillemin Chair.' n3 }7 |+ a/ T$ L
The researchers dubbed this new class of cells "region-selective pluripotent stem cells," or rsPSCs for short. The rsPSCs were easier to grow in the laboratory than conventional human pluripotent stem cells and offered advantages for large-scale production and gene editing (altering a cell's DNA), both desirable features for cell replacement therapies.6 h: V) W' ?7 H$ t' S+ l
To produce the cells, the Salk scientists developed a combination of chemical signals that directed human stem cells in a laboratory dish to become spatially oriented.
% q: G% Z2 X# D% N3 UThey then inserted the spatially oriented human stem cells (human rsPSCs) into specific regions of partially dissected mouse embryos and cultured them in a dish for 36 hours. Separately, they also inserted human stem cells cultured using conventional methods, so that they could compare existing techniques to their new technique.
5 u, i3 `3 a$ v0 |$ q7 N; U) `While the human stem cells derived through conventional methods failed to integrate into the modified embryos, the human rsPSCs began to develop into early stage tissues. The cells in this region of an early embryo undergo dynamic changes to give rise to all cells, tissues and organs of the body. Indeed the human rsPSCs began the process of differentiating into the three major cell layers in early development, known as ectoderm, mesoderm and endoderm. The Salk researchers stopped the cells from differentiating further, but each germ layer was theoretically capable of giving rise to specific tissues and organs.# s. E1 _& }4 Q- \. N
Collaborating with the labs of Salk Professors Joseph Ecker and Alan Saghatelian, the Izpisua Belmonte team performed extensive characterization of the new cells and found rsPSCs showed distinct molecular and metabolic characteristics as well as novel epigenetic signatures -- that is, patterns of chemical modifications to DNA that control which genes are turned on or off without changing the DNA sequence.
! o: |2 P1 d! l9 t& A"The region selective-state of these stem cells is entirely novel for laboratory-cultured stem cells and offers important insight into how human stem cells might be differentiated into derivatives that give rise to a wide range of tissues and organs," says Jun Wu, a postdoctoral researcher in Izpisua Belmonte's lab and first author of the new paper. "Not only do we need to consider the timing, but also the spatial characteristics of the stem cells. Understanding both aspects of a stem cell's identity could be crucial to generate functional and mature cell types for regenerative medicine."/ T1 n: Y, r! C* F# g' B2 V
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Story Source:+ ]' ^) Y; c7 k0 _- q
The above story is based on materials provided by Salk Institute for Biological Studies. Note: Materials may be edited for content and length.$ g) L! R; ^# j7 P' S3 N+ z
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/ f  p7 R2 `+ C  M0 l( j' QJournal Reference:
; V5 r' Z7 y1 w7 F$ P; m- Q/ ?        1        Jun Wu, Daiji Okamura, Mo Li, Keiichiro Suzuki, Chongyuan Luo, Li Ma, Yupeng He, Zhongwei Li, Chris Benner, Isao Tamura, Marie N. Krause, Joseph R. Nery, Tingting Du, Zhuzhu Zhang, Tomoaki Hishida, Yuta Takahashi, Emi Aizawa, Na Young Kim, Jeronimo Lajara, Pedro Guillen, Josep M. Campistol, Concepcion Rodriguez Esteban, Pablo J. Ross, Alan Saghatelian, Bing Ren, Joseph R. Ecker, Juan Carlos Izpisua Belmonte. An alternative pluripotent state confers interspecies chimaeric competency. Nature, 2015; DOI: 10.1038/nature14413
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